Blood-chapter 17

A. Functions of Blood

​1. Transport functions:​

​​a. Delivers oxygen from the lungs and nutrients from the digestive tract to cells

b. Transports metabolic wastes from cells to be eliminated

c. Transports hormones from endocrine glands to target organs

2. Regulatory functions:

​a. Maintain appropriate body temperature by heat distribution

​b. Maintain normal pH in body tissues, i.e. buffering systems

​c. Maintain adequate fluid volumes in circulation

3. Protective functions:

​a. Prevents blood loss

​b. Prevents infection by carrying immune components

      B. Components of Blood

-Blood is a fluid connective tissue, consisting of “cells with a non-living extra-cellular matrix”. The cells are the erythrocytes, leukocytes, platelets, and the fluid matrix is the plasma.

1. Physical Characteristics

​a. Blood is a sticky, viscous, opaque fluid with a metallic taste.

​b. Color varies from scarlet red (oxygen rich) to dark red (oxygen poor)

​c. Slightly alkaline ≈ 7.35 to 7.45

​d. At approximately 5L per adult, it makes up 8% of our body weight.

2.  Blood Plasma – Straw colored, sticky fluid.

​a. Components

​​1) Plasma is 90% water

​​2) Contains over 100 different solutes:

​​​a) nutrients

​​​b) gases

​​​c) hormones

​​​d) waste products

​​​e) proteins

​​​f) electrolytes (Na⁺, Cl⁻, etc)

​​3) Plasma proteins make up 8% of plasma weight. They include:

​​​a) Albumin – 60%, is a buffer and contributes to osmotic pressure

​​​b) Globulins – alpha, beta, gamma

​​4) Serum = plasma – clotting proteins

3. Formed Elements

​a.  Eyrthrocytes (RBC’s) – Hematocrit (40 – 45% of whole blood)

​​1)Physical description: VERY small - 7.5 µm in diameter

​​​- ≈5 million/mmᶟ (30 trillion per adult)

​​​- Shaped like a biconcave disc, making them very flexible with ​​​​   great ratio volume to surface area

​​​- Lifespan of approximately   120 days

​​2) Structural Organization:

​​​- bound by plasma membrane, but lack a nucleus and organelles

​​​-“bags” of hemogloblin (Hb) – 97%

​​​​-280 million Hb per RBC

​​​​-each Hb has four sub-units, each with 1 heme pigment bound ​​​​  to the protein globin

​​​​- red heme pigment contain 1 iron (Fe) at it’s center

​​​​-Hb also has a protein chain (2 α’s and 2 β’s)

​​​​-1 heme carries 1 O₂, so one Hb molecule carries 4 O₂’s,  thus one ​​​​  RBC carries 1 billion O₂

​​​​-12 – 18 g/100ml is normal Hb range

​​​- flexible and can change shape, squeezing through capillaries

​​​- great example of perfect form to function cell

​​​- generate ATP through anaerobic methods, preserving all oxygen

​​3) Function of Eyrthrocytes – dedicated to gas transport of O₂ and CO₂

​​​-Hb binds reversibly with oxygen, and is loaded in the lungs and heads ​​​  out to tissue cells.

​​​- When O₂ binds to iron, Hb is now called oxyhemoglobin and is bright ​​​   ruby red

​​​- In the body, when O₂ is released it is called deoxyhemoglobin and ​​​  becomes dark red

​​4) Production of Erythrocytes

​​​Hematopoiesis = Blood cell formation

​​​​-occurs in the red bone marrow

​​​Erythropoiesis = erythrocyte formation

​​​​a) Hematopoietic stem cell → myeloid stem cell → pro-​​​​​   erythroblast → series of nucleated cells → reticulocyte​​​​​    (non-nucleated) → erythrocytes

​​​​b) Process from stem cell to reticulocyte takes ≈ 15 days

​​​​c) Reticulocyte enters blood stream, and takes about two days to ​​​​   become mature erythrocyte.

​​​​d) New cells are produced at the rate of ≈ 2 million/second

​​​​e) Controlled by hormone Erythropoietin (EPO) – secreted by ​​​    ​     kidneys. Always some EPO in blood, but low O₂ levels prompt ​​​​     the kidneys to release more EPO

​​​​f) Adequate iron, B₁₂, and folic acid are all necessary

​​5) Fate of Erythrocytes – have useful lifespan of 100 – 120 days

​​​a) They become old and fragile, Hb degenerates, become trapped ​​​​b) Macrophages engulf and destroy old RBC’s

​​​​-Heme is separated from globin

​​​​​- Iron is recycled

​​​​​- Remaining heme degraded to yellow pigment bilirubin,​​​​​   eventually leaves with feces

​​​​​- Globin chain is metabolized back to amino acids

​​6) Erythrocyte Disorders – typically Anemia or polycythemia

​​​a) Anemia – “lacking blood” - condition in which the blood’s O₂ carrying​​​    capacity is too low. (It is a sign of a disorder, not a disease itself)

​​​       -people with anemia are often fatigued, pale, short of breath, cold​​​​  

​​b) Causes of anemia

​​​1) Blood Loss – Hemorrhagic anemia

​​​​Acute – rapid blood loss, stabbing, etc.

​​​​Chronic – slow, persistent blood loss, ulcer, etc.

​​​2) Not enough RBC’s being produced:

​​​​Iron Deficiency Anemia – inadequate intake of Fe ​​​​​​​​  or impaired Fe absorption​​​​​​​-Cells are microcytic/hypochromic

​​​​Pernicious Anemia – autoimmune disease, ↓B₁₂

​​​​​​​-Cells may be macrocytic

​​​​Renal Anemia – lack of EPO, due to renal disease

​​​​Aplastic Anemia – destruction of red marrow​​​​​​Often due to drugs/chemicals/radiation

​​​​3) Too many RBC’s destroyed - Hemolytic anemia

​​​​-RBC’s lyse prematurely, incorrect shape, Hbdefect​​​​​ bacteria, parasites, etc.

​​​​    -Thalassemia – typically Mediterranean descent. One ​​​​     of the globin chains is faulty or absent. RBC thin,​​​​​     delicate, and low in Hb.

​​​​​  -microcytic, hypochromic, hemolytic

​​​​   - Sickle-Cell anemia – change in one of the 146 amino ​​​​​acids in a beta chain of the globin molecule.

​​​​        - Causes misshapen RBC (crescent) when unloaded

​​​​        - RBC’s rupture easily, clog vessels – very painful

​​​​        - chiefly in black people in Malaria belt of Africa

​​c) Polycythemia – “many blood cells”

​​​-abnormal excess of RBC’s, increases blood viscosity.

​​​1) Polycythemia vera – bone marrow cancer characterized by ​​​    extremely high RBC count. (8 – 11 million/µl) Hematocrit as ​​​    high as 80%

​​​2) Secondary polycythemia results from low O₂ levels and ↑EPO

​​​3) Blood doping – artificially induced polycythemia

b. Leukocytes (WBC’s) – part of “buffy coat”, less than 1% of whole blood

​1) Only formed elements that are complete cells, contain nucleus & organelles

​​- 4,800 – 10,800 WBC’s/µl of blood, but produced 3X more than RBC’s

​2) Critical part of our defense system – can leave bloodstream (diapedesis) and ​    go to tissues to help bring out inflammation and immune responses.

​3) Leukocytoisis – elevated WBC level, normal response to infection

​4) Granulocytes: contain obvious membrane bound cytoplasmic granules

​​a) Neutrophils: most numerous WBC – 50 – 70% of leukocytes

​​​- twice as large as RBC’s

​​​- contain very fine lilac colored granules

​​​- multi-lobed nuclei ( 3 – 6 lobes)

​​​- phagocytic –“acute bacteria slayers”, attracted to inflammation

​​b) Eosinophils- only 2 – 4% of leukocytes

​​​- size of a neutrophil, two lobes connected by band

​​​- contain medium sized, red/orange granules

​​​- lead attack against parasites, aid in allergy/asthma response

​​c) Basophil- rarest of WBC’s , less than 1%

​​​- large course purple/black granules that contain histamine

​​​- nucleus is “U” or “S” shaped, but hidden by granules.

​​​- function to stimulate our inflammatory response.

​5) Agranulocytes: WBC’s that lack visible granules

​​a) Lymphocytes – 25% of leukocytes, second most numerous

​​​- large, dark purple nucleus that occupies most of cell

​​​   (will often see pale-blue rim of cytoplasm surrounding it)

​​​-  vary in size from small, medium and large

​​​- mediate immune response (B-cells and T-cells)

​​b) Monocytes – 3 – 8% of leukocytes, largest of all leukocytes

​​​-Dark purple nucleus, often U shaped or kidney shaped

​​​- can see abundant pale blue cytoplasm

​​​- highly mobile macrophages “big-eaters”, very phagocytic

​​​- crucial in our fight against viruses and chronic infections

​

​6) Production of Leukocytes:

​​Leukopoiesis – production of white blood cells

​​    a) Hematopoietic stem cell → Myloid or Lymphoid Stem cell →

​​​Myloid → Eosinophil, basophil, neutrophil & monocyte

​​​Lymphoid → B or T lymphocytes

​7) Leukocyte Disorders

​​a) Leukemia – “white blood” group of cancerous conditions involving ​​     overproduction of abnormal WBC’s

​​​- named for the cell type that is primarily affected (and cloned)a

​​​- myloid leukemia vs. lymphocytic leukemia

​​     1. Acute Leukemia – (quickly advancing) , derived from stem cells

​​​- primarily affect children, fatal in 3 – 6 months if untreated

​​     2. Chronic Leukemia – (slowly advancing),  from later cell stages.

​​​-primarily affects the elderly

​​​- slower and more responsive to treatment

​​b) Mononucleosis – “kissing disease” contagious viral disease

​​​-caused by the Epstein-Barr virus, excessive # of lymphocytes

​​​-symptoms include fatique, achy, sore-throat, low fever.

​​​-rest tends to be the only effective treatment.

​​​

c) Platelets – not truly cells, fragments of large cells called megakaryocytes.

​1) Small colorless fragments 150,000 – 400,000 µl

​2) Essential for the blood clotting process

​3) Hormone thrombopoietin regulates platelet formation

​

   C. Hemostasis – Blood Clotting (Coagulation)

​-fast, localized, and carefully controlled response to prevent blood loss from vessels

​1. 3 steps of hemostasis:

​​a) Step 1: Vascular spasm

​​​- damaged vessel responds to injury by constricting (vasoconstriction)

​​​- can limit blood loss for 20 – 30 minutes – most effective in small vessels.

​​b) Step 2: Platelet plug formation

​​​- When endothelium is damaged, and collagen fibers exposed, platelets stick

​​​-Platelets become activated, they swell, form spikes and become stickier

​​​-Release chemical messengers

​​​​ADP – causes more platelets to stick to area and release chemicals

​​​​Serotonin & thromboxane A₂ - enhance spasm and aggregation

​​​(Perfect example of positive feedback – enhancing original stimuli)

​​c) Step 3: Coagulation (blood clotting) – begins around 30 seconds after damage

​​​- reinforces the platelet plug with a fibrin mesh

​​​- Blood transformed from liquid to a gel in a multistep process using clotting ​​​   factors and procoagulants

​​​​1) Phase 1 – Two pathways to prothrombin activator

​​​​​Intrinsic and Extrinsic pathways exist, with typically both ​​​​​​occurring in the body. Outside of the body (test-tube) only the ​​​​​intrinsic exists.

​​​​​ -after multiple intermediate steps, both pathways cascade ​​​​​towards a common factor, and in the presence of Ca⁺ ions form ​​​​​Prothrombin activator

​​​​2) Phase 2 – Common pathway to thrombin

​​​​​- Prothrombin activator catalyzes the conversion of prothrombin​​​​​  into the active enzyme thrombin

​​​​3) Phase 3 – Common pathway to the Fibrin Mesh

​​​​​- Thrombin catalyzes the transformation of fibrinogen into ​​​​​ fibrin. The fibrin molecules join together to form long fibrin ​​​​​  strands. This glues the platelets together, and form the basis of ​​​​​  the clot. Fibrin makes the liquid plasma become gel-like and ​​​​​  forms a trap.

​​​​​- All of this requires the presence of Ca⁺ ions and a balance ​​​​​  between clotting factors and anticoagulants.

​​-Clot formation is normally complete within 3 – 6 min. after ​​  vessel injury.

​​​​4) Clot retraction – Within 30 -60 minutes the a process called clot   ​​​​retraction occurs, further stabilizing the clot. Platelets contain actin and ​​​​myosin proteins that are able to contract , pulling on the fibrin strands, ​​​​squeezing out serum, (plasma minus clotting proteins) and pulling the ​​​​edges together.

​   2. Hemostasis Disorders

​​a) Thrombus – a clot forms in an intact vessel and potentially occludes that vessel

​​​​- Coronary thrombosis

​​b) Embolus -  clot circulates freely in vessel. Not problematic until it encounters a ​​​​vessel with a smaller diameter and occludes it. At this point it is an ​​​​embolism. i.e. pulmonary embolism, cerebral emobolism → stroke

​​c) Anticoagulant drugs – prevent undesirable clotting

​​​​        ​aspirin, heparin, warfarin (Coumadin)

​​d) Bleeding Disorder – Thrombocytopenia – deficient platelets, causes spontaneous ​​​​​bleeding, petechiae.

​​​​​- Hemophilias – hereditary bleeding disorders, missing one or ​​​​​more clotting factors.

D. Blood Typing

​- Refers to the type of isoantigen (agglutinogen) present on the surface of the RBC

​  

​-Antigens are any substance capable of inducing the formation of an antibody, for immune ​  purposes.

​1. Isoantigens A, B, and Rh (D) are the focus. (although there are over 30 natural antigens ​​related to RBC’s)

​2. Isoantibodies –  proteins that can combine with and neutralize an antigen

​​- Isoantibodies (agglutinins) make RBC’s agglutinate (stick together, “clump”)

​​- Exist naturally in blood plasma

​3. ABO Blood groups are based on the presence or absence of two agglutinogens, type A and ​    type B

​​TYPE​​ANTIGEN (Agglutinogen)​     ANTIBODY(Agglutinins)

​​   A​​​A​​​   ​     Antibody B

​​   B​​​B​​​​     Antibody A

​​  AB​​​A and B​​​     Neither (universal recipient)

​​   O​​​Neither (universal donor)​     Both A & B

​4. Transfusion Reactions – When mismatched blood is infused, a transfusion reaction occurs

​​-recipient’s plasma antibodies attack donor’s RBC’s and cause them to agglutinate.

​​-Clogs small vessels, and then cells begin to rupture releasing hemoglobin

​​-When reaction severe, RBC are lysed almost immediately, leading to:

​​​a) low Oxygen carrying capacity

​​​b) clogged vessels hindering circulation beyond the obstruction

​​​c) freely circulating hemoglobin causing kidney damage and possibly renal ​​​   failure and death

​5. Rh Blood Group – 52 Rh agglutinogens exist, we focus on “D”

​​If Rh antigen is present, the person is Rh positive “+” ≈ 85% of population

​​If Rh antigen is not present, they are Rh negative “-“  ≈ 15% of population

​​a) Unlike the ABO system, No anti-Rh antibodies are produced UNLESS (-) blood is ​​    exposed to (+) blood

​​b) Hemolytic disease of the Newborn or Erythroblastosis fetalis

​​​1) Rh⁻  mother carrying Rh⁺ baby. At delivery when bleeding occurs, the mother ​​​    may be sensitized by her baby’s Rh⁺ antigens, and will start to form anti-Rh ​​​    antibodies.

​​​2) If mother becomes pregnant again, her antibodies can cause the placenta ​​​    and destroy the baby’s RBC’s. Causing anemia, hypoxia and possible death

​​​3) RhoGam ( a serum containing anti-Rh antibodies) is administered to Rh⁻ ​​​    mothers at approximately 28 weeks, that agglutinates the Rh factor, and ​​​    blocks her immune response. If baby is Rh⁺, she is given another dose within ​​​    72 hours after delivery.