Blood and Cardiovascular System Flashcards

Cardiovascular System

Components

• Blood: Connective tissue.
• Heart: A pump.
• Blood Vessels: Circulate blood between cells and the heart.
  • Elastic Arteries
  • Muscular Arteries
  • Arterioles
  • Capillaries
  • Venules
  • Veins

Diagram illustrating the flow of blood from the heart through arteries to tissues via capillaries, and back to the heart through veins.

Functions of Blood

Distribution

• Delivers O_2 to cells.
• Transports CO_2 to lungs.
• Transports nutrients.
• Transports hormones.
• Removes wastes from cells.

Regulation

• Maintains tissue pH.
• Maintains blood volume.
• Maintains body temperature.

Protection

• Prevents infection.
• Prevents blood loss.

Whole Blood

Composition

• Blood is a connective tissue consisting of:
  • Plasma:
    • Consists of water (90%) and solutes.
    • Represents 55% of the total blood volume.
  • Formed Elements:
    • Cells: erythrocytes (RBCs), leukocytes (WBCs), and cell fragments (platelets).
    • Represents 45% of the blood volume.

The vast majority of formed elements are red blood cells.

Hematocrit

• The portion (% by volume) of the blood that is composed of packed red blood cells.
  • Adult males: 47\% \pm 5\%.
  • Adult females: 42\% \pm 5\%.
    Note the buffy coat, which consists of leukocytes and platelets.

Normal Blood Volume Values (~8% of body weight)

• Adult males: 5-6 liters.
• Adult females: 4-5 liters.

Physical Characteristics

• Sticky, opaque.
• Salty.
• Color varies from scarlet (O2 rich) to darker red (O2 poor).
• 3-5 times more viscous than water.
• pH ranges between 7.35 – 7.45.
• Temperature ~ 38^\circ C.

Plasma

• The extracellular material of the blood.
• Consists of water (91.5%) and solutes (8.5%).

Solutes

Protein

• Albumin:
  • Most abundant of the plasma proteins (60%).
  • Produced by the liver.
  • Functions include:
    • Maintains osmotic pressure and controls water balance between interstitial fluid and the blood.
    • A transport protein for:
      • Hormones
      • Fatty acids
      • Unconjugated bilirubin
      • Drugs
    • Binds Ca^{2+}.
    • Serves as a buffer.
    • Scavenges free radicals.

Free radicals are chemical species that possess an unpaired electron in the outer shell of the molecule.

Functions of albumin: maintain fluid balance, transport, bind, buffer, scavenger.

Globulin

• 36% of the plasma proteins.
  • Alpha and beta globulins:
    • Produced by the liver.
    • Function as transport proteins for metal ions (Fe^{2+}, Cu^{2+}), cholesterol, complement proteins (important in immune function).
      Transferrin - Bound to Two Iron Atoms
  • Gamma ($\gamma$) Globulin:
    • Produced by plasma cells.
    • Are antibodies.
      Plasma cell makes antibodies. Antibodies bind to germ and work with other parts of the immune system to destroy the germ.

Clotting proteins

• 4% of the plasma protein.
• Made by the liver.
• Include fibrinogen, prothrombin, and others.
• Function: coagulation.

Organic Nutrients

• Glucose
• Amino acids
• Fatty acids, glycerol, triglycerides, cholesterol
• Vitamins

Erythrocytes

Functions

• Carry O2, CO2

Normal Values (At sea level)

• Adult males: 4.7 – 6.1 X 10^6/\mu l blood
• Adult females 4.2 – 5.4 X 10^6/\mu l blood.
  That’s about 83 billion/in^3

Why do men have a higher concentration of RBCs than women?

• Testosterone enhances RBC production.
• Estrogen suppresses RBC production.

Structure

• Diameter averages: 7.5 \mu m
• Biconcave discs.
• Organelles: none; are anucleate.

RBCs have a limited lifespan (120 days) and generate ATP anaerobically.

Important Proteins in RBCs

• Hemoglobin:
  • Carries CO2 and O2
• Maintains the biconcave shape but allows for change in shape (reversible deformity)
• Enzymes:
  • Antioxidant enzymes, glycolytic enzymes (Why?) and carbonic anhydrase
• Spectrin:

Erythrocytes are shaped like biconcave discs (maintained by cytoskeletal elements including spectrin, ankyrin).

The flattened biconcave shape provides maximum surface area for the diffusion of gases into and out of the cell.

What happens to the shape of RBCs when people have defective or absent spectrin or ankyrin? They assume a more rounded shape and are called spherocytes.

What erythrocyte characteristics enhance the gas transporting ability of an erythrocyte?

• Small size, lots of surface area (biconcave shape).
• Presence of hemoglobin.
• Anaerobic metabolism (they do not consume the O_2 that they carry).

Hemoglobin

Functions

Carries up to 4 molecules of O_2

Lungs HHb + nO2 \rightleftharpoons Hb(O2)n + H Tissues

oxyhemoglobin

(deoxyhemoglobin)

Carries up to 2 molecules of CO_2

Tissues HHb + nCO2 \rightleftharpoons Hb(CO2) n Lungs

reduced hemoglobin

carbaminohemoglobin

Other functions

• Carries NO (nitric oxide), a vasodilator.
• Buffers H^+.

Hb has a much greater affinity (200X) for carbon monoxide (CO) than O_2. Why is CO so toxic? Hb + CO \rightarrow carboxyhemoglobin (bright purple)

Normal Values

• Adult males: 14-20 g/100 ml blood
• Adult females: 13-18 g/100 ml blood
• Infants: 12-16 g/100 ml blood

Location

• Found only within erythrocytes

Why is it advantageous for hemoglobin to reside in RBC’s?

1. Prevents degradation and leakage into tissues and urine.
2. Prevents it from contributing to viscosity and osmotic pressure. Remember hemoglobin is a protein!

Hemoglobin Variants

• HbA1 \alpha2 \beta2 comprises about 96% of all adult hemoglobin
• HbA2 \alpha2 \delta2 comprises < 2% of adult hemoglobin
• HbF \alpha2 \gamma2 comprises < 2% of adult hemoglobin but is the dominant form in the fetus
  • it is gradually replaced by HbA after birth

Hemoglobin A1c is a glycated hemoglobin (glucose binds to a terminal valine of the β chain). Elevated Hb A1c levels are associated with uncontrolled diabetes mellitus.

Fetal hemoglobin has higher O_2 affinity than adult hemoglobin. Is this an advantage for the fetus?

Sickle cell anemia is an inherited disorder in which abnormal hemoglobin is produced. The disease results from a mutation in the β-globin gene. The abnormal hemoglobin causes red blood cells to assume a sickle shape.

Erythropoiesis

• Hematopoiesis: blood cell formation
• Fetal Sites: yolk sac, liver, spleen, red bone marrow (after 19 weeks)
• Adult Sites: red bone marrow of the ribs, sternum, vertebrae, pelvis, scapulae, skull, proximal humerus and proximal femur

What happens to cell size during erythropoiesis?

Cell gets smaller.

What happens to cell color during erythropoiesis?

Cells develop red color.

What happens to organelles during erythropoiesis?

Organelles degraded and nucleus is extruded.

What happens to cell number during erythropoiesis?

Increases, due to mitosis of hemocytoblasts and proerythroblasts.

What do you think an elevated reticulocyte count might indicate?

Predict what might happen to the recticulocyte count during the week after a person has donated blood.

Nutritional requirements for erythropoiesis

Iron

• Needed for hemoglobin synthesis

Vitamin B12

• DNA Synthesis
  absorption requires the presence of IF (intrinsic factor) produced by parietal cells of the stomach lining

Other Nutrients

Erythrocyte Degradation

• Erythrocyte life span is 100-120 days.
• Damaged, aged, or defective erythrocytes are engulfed by macrophages of the liver, spleen, and bone marrow

Macrophages engulf and destroy erythrocytes

hemoglobin --> heme --> Iron (recycled or stored)

globin --> amino acids to the liver

heme --> biliverdin --> bilirubin --> bile --> stercobilin (feces) and urobilinogen --> urobilin (kidneys)

Erythrocyte Disorders

Polycythemia

• Excess number of RBCs (> 7X10^6/mm^3)

Anemia

1. Any condition in which the blood has abnormally low O_2 carrying capacity
2. Causes include reduced numbers of RBCs, reduced concentration of hemoglobin or synthesis of abnormal hemoglobin

What are some causes?

• Reduced rate of erythropoiesis
• Excessive hemolysis
• Excessive bleeding

Classification of anemias

1. Those based on RBC morphology:

   • Red blood cell size

     • microcytic (small cells)
     • normocytic (normal size)
     • macrocytic (large size)

   • Red blood cell color

     • hypochromic (pale cells)
     • normochromic (normal color)
     • hyperchromic (dark cells)

   • Hypocytic, hypochromic Anemia (Iron deficiency)

   • Hypercytic, normochromic Anemia (Autoimmune hemolytic)

Anemias Caused By Reduced Erythrocyte Number

• Hemorrhagic Anemia
• Hemolytic Anemia
• Aplastic Anemia

Anemias Caused By Reduced Hemoglobin or Abnormal Hemoglobin

• Iron deficiency anemia
• Pernicious anemia
• Sickle cell anemia
• Thalassemia

Leukocytes

Normal Values

• Less than 1% of total blood volume
• Adults: 4800 – 10,800 leukocytes /mm^3 blood (higher values in newborns, infants and children)

Structure

• Are nucleated
• Contain organelles
• Diameters range from 8 – 24 \mu m
• May contain cytoplasmic granules (agranulocytes vs. granulocytes)

Leukocyte Classes

Granulocytes

• Neutrophil (also called a polymorphonuclear cell)

  • diameter = 10-12 \mu m
  • cytoplasmic granules stain pale lavender
  • lobed nuclei (3-6 lobes)
  • Granules contain lysosomal enzymes and defensins

Neutrophils are quick acting phagocytes (1st responders). They are quick but weak! % of total leukocytes: 50-70%

• Eosinophil

  • diameter = 10-14 \mu m
  • large granules which stain red (major basic protein)
  • bilobed nucleus
  • represent 2-4% of the total WBC count
  • Granules contain digestive enzymes

Are antiparasitic and anti-allergy

• Basophil

  • diameter = 8-10\mu m
  • large granules which stain blue
  • U or S shaped nucleus
  • 0. 5 – 1% of total WBC
  • Granules contain:

histamine which induces inflammation and vasodilation and heparin an anticoagulant

Agranuloctes

• Lack visible cytoplasmic granules

• Lymphocyte

  • diameter 5-8 \mu m (small), 10-12 \mu m (medium) or 14-17 \mu m (large)
  • 20-25 % of the total WBC count
  • large, deep blue or slightly indented nucleus
  • thin rim of pale blue cytoplasm

T lymphocyte (T cells) fight antigens directly. B lymphocytes (B cells) divide to produce plasma cells that secrete antibodies

• Monocytes

  • diameter = 18 \mu m
  • nucleus is U shaped or kidney shaped
  • abundant pale blue cytoplasm
  • 3 – 8 % of the total WBC

Are phagocytes – slow but strong. Develop into macrophages when they migrate into connective tissue

Leukopoiesis

• Leukopoiesis is the production of leukocytes
• All leukocytes can be made in red bone marrow from hemocytoblasts
• Lymphocytes can be made in either red bone marrow or lymphoid tissues
• The production of lymphocytes is stimulated by interleukins and by colony stimulating factors (CSFs)

White Blood Cell Disorders

• Leukopenia: circulating WBC count <4000/mm^3 blood in adults

increases the susceptibility to infection. causes include bone marrow depression or destruction, often due to drugs, radiation, infection, or autoimmune conditions

• Leukocytosis: circulating WBC count is >11,000/mm^3 blood in affected adults;

Is accompanied by bleeding, weight loss, liver/spleen/lymph node enlargement or immunosupression; suspect primary bone marrow disease. Causes include infection, inflammation, malignancy, allergic reactions, autoimmune disorders, genetic disorder, extreme stress, other causes

Leukemia

• Cancer in which an excessive number of white blood cells is produced
• Classification:
  • Acute: disease progresses rapidly
    • Myelocytic: involves cells in the myeloid pathway
    • Lymphocytic: involves cells in the lymphocytic pathway
  • Chronic: disease progresses slowly

Causes: cancer in which an abnormally high number of WBCs are produced. Symptoms anemia, fever, bruising/bleeding, bone pain

Infectious Mononucleosis

• B lymphocytes are infected and proliferate in an uncontrolled manner
• Signs include sore throat, fever, enlarged lymph nodes.
• Enlarged spleen, lethargy, fatigue
• Cause: Epstein Barr Virus

Platelets

Structure

• Are cell fragments
• Discoid in shape; diameter is 2-4 \mu m
• Major internal proteins are actin and myosin

What are actin and myosin used for?

Contraction

• Cytoplasmic storage granules:
  • \alpha granules contain fibrinogen, factor V, factor VII, von Willibrands factor, platelet factor 4 and PDGF
  • Dense granules contain serotonin, Ca^{2+}, adenosine nucleotides (ATP and APD), thromboxane A2 (a prostaglandin)

Function

• Hemostasis

Platelet Production

• Platelets are produced in red bone marrow from megakaryotyctes
• Production is regulated by thrombopoietin and interleukins
• Production takes 4-5 days; life span is 5-10 days
• Average adult values: 150,000-400,000/mm^3 blood
• An additional 1/3rd is stored in the spleen

Hemostasis

• Hemostasis: stoppage of bleeding

• Mechanisms:

  1. Vascular Spasm: constriction of the damaged blood vessel
  2. Platelet Plug: platelets adhere to each other and to the wall of the injured vessel to form a temporary seal
  3. Coagulation: blood is transformed into a semisolid mass that surrounds and strengthens the platelet plug

Platelet Adhesion depends on the presence of Von Willibrands Factor, made by platelets and endothelial cells

Von Willebrand Disease: Increased bleeding time; normal platelets. Normal platelet count, but defective adhesion Resulting in prolonged bleeding time

Secondary Hemostasis: Coagulation

• The goal of coagulation is to form a fibrin meshwork!

• The formation of a blood clot takes place in three phases:

  1. Formation of Prothrombin Activator (prothrombinase)
  2. Conversion of Prothrombin to Thrombin
  3. Polymerization of Fibrinogen to Fibrin

Slower pathway (3-6 minutes) shorter pathway (about 15 seconds). All necessary factors are in the blood. Injured cells external to the blood release tissue factor (TF) which shortens the process

• Intrinsic Pathway
• Extrinsic Pathway

What ion is needed in both pathways?

Ca2+

When blood coagulation happens in a test tube, is the extrinsic or the intrinsic pathway activated?

intrinsic

Antithrombin III inhibits activated Factor X – which pathway is inhibited – intrinsic, extrinsic or both?

both pathways

Agents Used Clinicallyto Prevent Clotting

• Aspirin (reduces thromboxane production)
• Heparin Sulfate (activates antithrombin III)
• Warfarin and Coumadin, vitamin K inhibitors

How do these work?

Blood banks routinely add calcium chelators to blood. Calcium chelators remove calcium from solution. Why do they add these chelators?

Disorders Related to Hemostasis

• Thrombus: a clot that develops and persists in an unbroken vessel or chamber of the heart
• Embolus: an intravascular clot that is floating free in the plasma
• Disseminated Intravascular Coagulation: a systemic thrombohemorrhagic disorder involving unregulated fibrin formation and accelerated fibrinolysis
• Thrombocytopenia: A platelet count of <50,000 /mm^3 blood which may cause spontaneous bleeding
• Hemophilia: Deficient coagulation factor VIII (hemophilia A), IX (hemophilia B), factor (XI) or others

Measurement of blood clotting

• Prothrombin Time (PT)
  • Measures clotting time of plasma in the presence of an optimal concentration of tissue factor
  • Measures the overall efficiency of the extrinsic clotting system and the common pathway
  • Increased PT time may indicate deficiency of prothrombin, fibrinogen, or factors V, VII, or X
• Partial Thromboplastin Time (PTT)
  • Measures the overall efficiency of the intrinsic pathway and the common pathway
  • PTT is prolonged in deficiencies of factors V, VIII, IX, X, XI, XII, HMW kininogen, heparin, prekallikrein, prothrombin, fibrinogen

PT

• Extrinsic pathway
• Factor VIIa, tissue factor
  PPT
• Intrinsic pathway
• Factors VIIIa, IXa, Xla calcium, phospholipid

PT and PPT

• Prothrombinase complex
• Factors Va, X, calcium, phospholipid

Thrombin Time

• Prothrombin --> Thrombin
• Factor XIII --> Factor XIIIa
• Soluble fibrin --> Insoluble fibrin

Blood Groups

• Agglutinogen: a glyoprotein found on the surfaces of RBCs -

agglutinogens elicit immunologic responses, such as antibody formation, when introduced into a non-compatible host

• Agglutinin: a glyoprotein antibody produced by plasma cells and found in body fluids

Agglutinins are produced by non-compatible hosts when they are exposed to foreign aglgutinogens

• Agglutination: a clumping reaction that occurs when agglutinogens are linked to agglutinins

Clinically Important Blood Groups

• The ABO System
• the Rh System

The ABO System

The Rh System

• Landsteiner and Alexander Weiner discovered the Rh factor
• The Rh System includes several agglutinogens: Include C,D,E,c,e
• D is the most immunogenic even though C and E are somewhat immunogenic

It was called the Rh factor because it was first found on blood cells isolated from a Rhesus monkey.

• Rh positive individuals have C,D,E in some combination
• Rh negative individuals have no C, D or E
• Rh negative individuals will develop anti Rh agglutinin (usually anti-D) if exposed to Rh positive blood

Dad-- inject Rh + blood. Produce anti-D agglutinin.

Hemolytic Anemia of the Newborn -HDN (Erythroblastosis Fetalis)

• A disorder that may arise when a mother lacks an agglutinogen that is present on the RBCs of her fetus. The usual cause is an Rh incompatibility.
• Mother: Rh negative
• Father: Rh positive
• Fetus: Rh positive

The process: Rh negative mother carrying an Rh positive fetus

• Fetal Rh+ cells pass into the mothers bloodstream as a result of bleeding either during the pregnancy or during the birth process
• Mother’s plasma cells produce anti-D agglutinin
• Anti-D agglutinin can diffuse through the placenta and into the fetus during subsequent pregnancies
• The anti D agglutinin will attack the fetal cells, causing hemolysis

The severity of the symptoms will depend on the amount of agglutinin produced by the mother and the amount of time that the the fetus is exposed to it.

Specific problems include:

1. Anemia, hypoxia (can lead to brain damage, death)
2. Hyperbilirubinemia
3. Kernitcterus
4. Hepatosplenomegaly
5. Fetal ascites/edema

Treatment includes in utero transfusions, early induction of labor and exchange transfusions, phototherapy after birth

Prevention involves the administration of Rhogam to Rh negative mothers

Hemolytic Transfusion Reactions

Reasons for Mismatches:

1. Human Error
2. Weak agglutinogens missed in typing
3. Atypical groups