Erythropoiesis Regulation & Kidney Function

Chapter 17: Blood

• Blood exits the heart via arteries.
• Arteries branch into capillaries which are one cell thick.
• Oxygen and nutrients diffuse across capillary walls and into organs.
• Carbon dioxide and waste from organs enter the bloodstream.
• Oxygen-deficient blood leaves the capillary bed and flows into veins.
• Veins return to the heart and drain into the heart.
• Chapter 17 covers topics like :
  • Blood composition and functions
  • Blood plasma
  • Formed elements
  • Homeostasis
  • Transfusion and Blood Replacement
  • Diagnostic blood tests
  • Developmental Aspects of Blood

Blood Composition and Functions

• Blood is a fluid connective tissue.
• Plasma is the non-living fluid matrix of blood.
• Formed elements are the living blood "cells" suspended in plasma.
• Erythrocytes are red blood cells, or RBCs.
• Leukocytes are white blood cells, or WBCs.
• Platelets are cell fragments.
• A spun tube of blood yields three layers which include:
  • Plasma at the top (~55%)
  • Erythrocytes at the bottom (~45%)
  • WBCs and platelets in the Buffy coat (<1%)
• Hematocrit is the percent of blood volume that is RBCs.
  • 47% ± 5% is the normal range for males
  • 42% ± 5% is the normal range for females
• Blood is a sticky, opaque fluid with a metallic taste.
• Blood color varies with O2 content.
  • High O2 content is scarlet
  • Low O2 content is dark red
• Blood pH ranges from 7.35–7.45.
• Approximately 8% of body weight is blood.
• Average blood volume is 5–6 L for males and 4–5 L for females.
• Functions of blood include:
  • Distributing substances
  • Regulating blood levels of substances
  • Protection
• Blood's distribution functions include:
  • Delivering O2 and nutrients to body cells
  • Transporting metabolic wastes to lungs and kidneys for elimination
  • Transporting hormones from endocrine organs to target organs
• Blood's regulation functions consist of:
  • Maintaining body temperature by absorbing and distributing heat
  • Maintaining normal pH using buffers and alkaline reserves of bicarbonate ions
  • Maintaining adequate fluid volume in the circulatory system
• Blood's protection can be done by;
  • Preventing blood loss: Plasma proteins and platelets initiate clot formation
  • Preventing infection: Antibodies, complement proteins, and WBCs

Blood Plasma

• Blood plasma is approximately 90% water.
• Plasma contains over 100 dissolved solutes
• Solutes found in blood plasma:
  • Nutrients
  • Gases
  • Hormones
  • Wastes
  • Proteins
  • Inorganic ions
• Plasma proteins are the most abundant solutes and are mostly produced by the liver.
• Remain in blood; not taken up by cells.
• Composition varies as cells remove or add substances but homeostatic mechanisms work to keep it relatively constant.
• When blood protein levels drop, the liver makes more.
• When blood becomes too acidic, the lungs and kidneys work to restore pH.
• Plasma proteins consist of:
  • 60% albumin
  • 36% globulins
  • 4% fibrinogen
• Albumin makes up 60% of plasma protein.
• Functions of Albumin consist of:
  • Major contributor of plasma osmotic pressure
  • Substance carrier
  • Blood buffer

Formed Elements

• Formed elements are living blood cells suspended in plasma.
• Formed elements include:
  • Erythrocytes, or RBCs
  • Leukocytes, or WBCs
  • Platelets, which are cell fragments
• All blood is made in bone marrow
• Only WBCs are complete cells.
• RBCs have no nuclei or other organelles.
• Platelets are cell fragments.
• Most formed elements survive in the bloodstream for only a few days.
• Most blood cells originate in bone marrow and do not divide.
• Erythrocytes (RBCs) are biconcave discs, anucleate, essentially no organelles.
• Diameters larger than some capillaries.
• Filled with hemoglobin (Hb) for gas transport.
• Contain plasma membrane protein spectrin and other proteins.
• Major factor contributing to blood viscosity which can make blood thinner or thicker
• Erythrocytes contribute to gas transport.
• Biconcave shape supports a huge surface area relative to volume.

• 97% hemoglobin, not counting water.

• Erythrocytes lack mitochondria so ATP production is anaerobic; they do not consume O2 they transport.
• RBCs dedicated to respiratory gas transport.
• Hemoglobin binds reversibly with oxygen.
• Normal values for blood gas are:
  • Males- 13-18g/100ml
  • Females - 12-16 g/100ml
• Hemoglobin structure is:
  • Globin, composed of 4 polypeptide chains (Two alpha and two beta chains)
  • Heme pigment bonded to each globin chain, this gives blood red color
  • Heme's central iron atom binds one O2
• Each Hb molecule can transport four 02.
• Each RBC contains 250 million Hb molecules, or 1 billion molecules of oxygen.
• Hemoglobin functions:
  • O2 loading in the lungs produces oxyhemoglobin (ruby red)
  • O2 unloading in tissues produces deoxyhemoglobin or reduced hemoglobin (dark red)
  • CO2 loading in tissues results in 20% of CO2 in blood binding to Hb or carbaminohemoglobin
• Hematopoiesis is blood cell formation in the red bone marrow.
• The red bone marrow is composed of reticular connective tissue and blood sinusoids.
• In adults, hematopoiesis is found in the axial skeleton, girdles, and proximal epiphyses of the humerus and femur.
• Hematopoietic stem cells (Hemocytoblasts) give rise to all formed elements.
• Hormones and growth factors push cells toward a specific pathway of blood cell development.
• Committed cells cannot change and new blood cells then enter blood sinusoids.
• Erythropoiesis is Red Blood Cell Production
• Erythropoiesis contains different stages
  • Myeloid stem cells transform into proerythroblasts
  • In 15 days proerythroblasts develop into basophilic, then polychromatic, then orthochromatic erythroblasts, and then into reticulocytes
• Reticulocytes enter the bloodstream, and mature RBCs in as little as 2 days
• Erythropoiesis :
  • as myeloid stem cells transform
  • Ribosomes synthesized
  • Hemoglobin synthesized; iron accumulates
  • Ejection of nucleus; formation of reticulocyte (young RBC) is observed
• Reticulocyte ribosomes degraded; Next is to become mature erythrocytes are created
• There's regulation in Erythropoiesis
• Too few RBCs lead to tissue hypoxia
• Too many RBCs increases blood viscosity

• 2 million RBCs made per second

• Balance between RBC production and destruction depends on hormonal controls, adequate supplies of iron, amino acids, and B vitamins.
• Erythropoietin (EPO) is a needed hormone
• Essential in Direct stimulus for erythropoiesis
• There is always a small amount in blood to maintain basal rate
• Released by kidneys and liver in response to hypoxia
• Causes of hypoxia include decreased RBC numbers due to hemorrhage or increased destruction
• Insufficient hemoglobin per RBC (e.g., iron deficiency)
• Reduced availability of O2 (e.g., high altitudes)
• Effects of EΡΟ includes:
  • Rapid maturation of committed marrow cells
• Increased circulating reticulocyte count in 1–2 days
• Testosterone enhances EPO production which results in higher RBC counts in males
• Dietary Requirements for Erythropoiesis is Nutrients-amino acids, lipids, and carbohydrates
• Iron is available in diet and contains 65% in Hb; rest in liver, spleen, and bone marrow
• Vitamin B12 and folic acid is necessary for DNA synthesis for rapidly dividing cells by developing RBCs
• Fate and Destruction of Erythrocytes take 100-120 days
• There's no protein synthesis, growth, division
• Old RBCs become fragile and Hb begins to degenerate so it should be degraded
• Anemia is where Blood has abnormally low O2-carrying capacity
• Usually accompanied by fatigue, pallor, shortness of breath, and chills
• Anemia contains three broad groups which include:
  • Blood loss
  • Low RBC production
  • High RBC destruction
• Hemorrhagic anemia consists of rapid blood loss which is treated by blood replacement
• In Iron-deficiency anemia, the following occurs :
  • Caused by hemorrhagic anemia, low iron intake, or impaired absorption
• There are Iron supplements to treat
• Pernicious anemia Autoimmune attacks stomach or Intrinsic factor to absorb vitamin 12
• In Renal anemia, there's lack of EPO, often accompanies renal disease, and it treated with synthetic EPO
• Thalassemia is typically of Mediterranean ancestry One globin chain absent or faulty and the severity ranges from mild to severe
• Causes of Anemia: High RBC Destruction - Sickle-cell is genetic defect in Hemoglobin S which one amino acid wrong causes cells to be block small vessels and have hard time unloading O2

Leukocytes

• Leukocytes make up less than 1% of total blood volume.

• Normal Leukocyte numbers range from approximately, 4,800 - 10,800 WBCs/ µl blood.

• It's function to be in defense against disease.

• Can leave capillaries via diapedesis.

• Move through tissue spaces by ameboid motion and/or positive chemotaxis.

• Leukocytosis is a WBC count over 11,000/mm3.

• The normal response to infection is Leukocytosis:WBC

• The two categories of Leukocytes include:

  • Granulocytes: Visible cytoplasmic granules with Neutrophils, eosinophils, and basophils

• Agranulocytes: No visible cytoplasmic granules with Lymphocytes and monocytes

• Granulocytes are larger and shorter-lived than RBCs and have Lobed nuclei with All phagocytic to some degree

• Neutrophils are the most numerous WBCS that stain lilac and are called Polymorphonuclear leukocytes

• Eosinophils have Red-staining granules that Release enzymes to digest parasitic worms and Role in modulating immune response

• Basophils make up the - Rarest WBCs that have inflanmatory chemicals such as Histamine

• Agranulocytes are Agranulocytes that lack visible cytoplasmic granules, but have kidney shaped nuclei

• There are two types Lymphocytes, Virus T and B

  • large dark pruple circular nucli that Crucial to immunity mostly in lymphod

• Monocytes largest that differenciate phagosyitic cell

• Leukopoiesis Production of WBCS is Stimulated by 2 chemical that will All leukocytes originate from them Lymphoid stem cells lymphocytes that diffferent that live long to decades

Hemostasis

• Hemostasis is a fast series of reactions for stoppage of bleeding

• Requires clotting factors, and substances released by platelets and injured tissues

• There's Three steps in hemostasis

  • Vascular spasm
  • Platelet plug formation
  • Coagulation which equals blood clotting

• Hemostasis consist of a Vasoconstriction of damaged blood vessel that is usually triggered by:

  • Direct injury to vascular smooth muscle
  • Chemicals released by endothelial cells and platelets
  • Pain reflexes

• Most effective in smaller blood vessels

• Hemostasis includes platelet plug formation with Damaged endothelium exposing collagen fibers

• Hemostasis triggers Positive feedback cycle causing Platelets to stick to collagen fibers via the plasma protein von Willebrand factor

• Swell, also become spiked and sticky, and release chemical messengers ADP which causes platelets to stick and release their contents.

• Serotonin and thromboxane A2 enhance vascular spasm and platelet aggregation

• Coagulation phase consist os series of reactions using clotting factors

• Coagulation includes Three phases of that occurs

  • Prothrombin activator formed in both intrinsic and extrinsic pathways that becomes
  • Prothrombin converted to enzyme thrombin
  • Thrombin catalyzes fibrinogen to fibrin
    • Three phases of which is called coagulation

• There are Factors Limiting Clot Growth or Formation There consists of two:

  • Swift removal and dilution of clotting factors

• Inhibition of activated clotting factors

• Platelet adhesion needs to be be prevented

  • Platelets need to be to cling from the vessel itself

• Fibrinolysis Removes unneeded clots after healing by tissue plasmogene

• Thromboembolic disorders : undesirable that causes the emobli and thrombo. is not normal

• Bleeding disorders : abnormalities that lead from normal clots to disorders

• Thrombocytopenia: where number of low circulating need petichia that is supporession of bone marrow

• Hemophilia is disorder from hereditary caused by 8,9, etc blood clotters which treated factor 8,9 by blood

Transfusion and Blood Replacement

• Involves both types of disorders that is a pregnancy comprision to blood and tissue

Explore the regulation of erythropoiesis, focusing on the role of erythropoietin (EPO) and kidney function. Questions cover EPO secretion, effects on bone marrow, and responses to hypoxia. Understand factors affecting oxygen-carrying capacity and consequences of kidney damage.