Blood 2
(-blast def
(-blast) means that this cell is active in cell division
Erythroblasts: Reticulocyte
(contains 80% of the Hb a mature RBC has) Nucleus has been ejected; small fragments of the RER remain (thus the name, reticulocyte for reticulum) Matures two days in bone marrow before entering the circulation. Account for 0.8% of RBC population in the circulation
Hypoxia
(oxygen deficiency). Kidneys release erythropoietin (EPO) which acts on the bone marrow to stimulate RBC production when the kidneys are exposed to low oxygen concentration. Anemia (due to hemorrhage or excessive RBC destruction). Insufficient hemoglobin per RBC (iron deficiency) Decreased blood flow to kidneys Decrease in oxygen content of air in lungs Disease (pneumonia) Non Pathological form is High Altitude Hypoxia Under maximum EPO stimulation, bone marrow can increase rate of erythropoiesis 10 X (30 million cells/second.
Hemoglobin and Oxygen & Carbon Dioxide Transport: list
(oxyhemoglobin) (deoxyhemoglobin). carbaminohemoglobin).
Regulation of Erythropoiesis
...
Red Blood Cell Recycling: numbers replaced
1% of RBCs are replaced daily at a rate of 3 million/second or 100 billion new RBCs/day.
hematocrit in female n why
37-47% in females (estrogens do not stimulate RBC production)
hematocrit in male n why
40-54% in males (androgens stimulate RBC production—enhance EPO production)
Hemorrhagic anemia
: loss of RBCs due to bleeding: Chronic conditions such as bleeding ulcers. Acute conditions due to injury. Blood loss may be prolonged from chronic conditions such as bleeding ulcers, or acute resulting from traumatic injury.
Hemocytoblast fn
Able to divide and produce more hemocytoblasts, or Give rise to other -blast cell types which give rise to the various mature blood cells (RBCs, WBCs, platelets).
formed elements origin etc
After birth, the formed elements are produced in the red marrow of certain bones and are released into the circulation after completing their development.
Hemocytoblast def
All erythrocytes, leukocytes and platelets are derived from this pluripotent stem cell
Diseases of the Blood RBCs: list
Anemia: Hemorrhagic anemia: Hemolytic anemia Aplastic anemia Sickle-Cell anemia Polycythemia
What Happens to Biliruben After it is Squirted into the Intestine as Bile?
Bacteria in large intestine convert biliruben to urobilinogens and stercobilinogens.
Erythroblasts
Begin synthesizing hemoglobin Size of nucleus decreases Amount of hemoglobin increases. Polychromatophilic erythroblast has a mixture of RER (stains blue) and hemoglobin (stains red)
Erythropoiesis: site of erythropoiesis in big fetal
Once fetal skeleton is large enough, erythropoiesis takes place in the red marrow of certain bones.
What Happens to the Iron in Heme?
Free iron is toxic to cells Iron is transported in bloodstream bound to transferrin. Iron-transferrin in bone marrow dissociates and newly forming RBCs pick up the iron. Excess iron is stored bound to protein as ferritin or hemosiderin in the liver and spleen.
Hemopoiesis: def
General Term for Blood Cell Production
urobilin: fn, where
Gives urine its yellow color Also found in feces with stercobilins which give feces its color.
process
Globin is broken down and amino acids are recycled. Iron is removed from the heme units. The pigments biliverdin (green) and biliruben are transported to the liver bound to albumin in the plasma for excretion in bile and is eventually eliminated in the feces.
oxyhemoglobin
Hb of RBCs is "loaded" with oxygen in the lungs. Oxygen depleted blood enters the lungs. Oxygen diffuses out of the air sacs into the blood and then into the RBCs where it binds to Hb (oxyhemoglobin)
Hemoglobin Structure
HbO2 (Oxyhemoglobin) has oxygen molecule weakly bound to the iron. Deoxyhemoglobin Carbaminohemoglobin
hemoglobin fn
Hemoglobin binds easily & reversibly with oxygen, and most oxygen carried in the blood is bound to Hb.
hemoglobin consists
Hemoglobin consists of the protein globin (four polypeptide chains) and each is attached to the red heme pigment. Each heme has an iron atom, and each iron can bind a molecule of oxygen.
Erythropoiesis: site of erythropoiesis in adults
In adults, erythropoiesis occurs in the red marrow of the vertebrae, sternum, ribs, skull, scapulae, pelvis and proximal long bones.
iron overload
In iron overload, cardiac muscle cells become secondary storage sites. This condition is linked to heart disease.
Proerythroblasts
Large nucleus; blue cytoplasm
RES fn
Once the biconcave shape of RBCs is lost, they are removed by the reticular endothelial system (RES). The RES is a meshwork of fibers making up the stroma of the liver and spleen and containing fixed macrophages that have the ability to detect abnormalities in old red blood cells.
Hematocrit: def
Percentage of whole blood volume contributed by formed elements (99.9% of which are RBCs).
Pernicious anemia def
Pernicious anemia is an autoimmune disease where the body lacks intrinsic factor which is required to absorb vitamin B-12 from food.
Pernicious anemia treatment
Pernicious anemia is easily treated with vitamin B-12 shots.
Hemolytic anemia:
Plasma membranes rupture and the Hb leaks out. In hemolytic anemia, the plasma membranes of RBCs become fragile due to exposure to toxins, poisons, parasites and transfusion with the wrong blood type. When the RBCs try to squeeze through capillary beds, the membranes rupture and the hemoglobin leaks out.
Polycythemia def
Polycythemia is a blood disease in which there are too many erythrocytes resulting in the blood becoming viscous or thick. Hematocrit is elevated significantly above 55% The increase in viscosity results in high blood pressure, strain on the heart, and clot formation. There are several causes underlying polycythemia.
Polycythemia: list
Polycythemia vera Secondary polycythemias
Polycythemia vera
Polycythemia vera is a bone marrow cancer characterized by a high RBC count in which the concentration of RBCs reaches 8-11 million cells per microliter. The normal hematocrit (measure of the percentage of RBCs/volume of blood) is around 45%, however in polycythemia vera, the hematocrit can reach 80%. Blood volume may double & circulation becomes impaired
Stages of RBC Maturation: list
Proerythroblasts Erythroblasts - Normoblast - Reticulocyte Mature erythrocyte
Erythropoiesis
RBC Production
blood doping
Recently, a new type of secondary polycythemia has been identified as blood doping which is practiced by some athletes competing in demanding events.
hematocrit reported as
Reported as volume of packed RBCs (VPRC) or packed cell volume (PCV).
Red Blood Cell Recycling: travel time
Round trip from heart to tissues and back to heart takes less than 1 minute. Travels 700 miles during its 120 day life span Subject to a great deal of wear and tear
Secondary polycythemias
Secondary polycythemias result when less oxygen is available. or EPO production increases. This condition can occur as a normal response in people living at high altitudes.
urobilinogen
Some urobilinogen is absorbed into blood and is excreted in urine. Converted to urobilin upon exposure to oxygen
removal of rbc balance
The destruction and removal of old RBCs is balanced by production of new RBCs in bone marrow.
Red Blood Cell Recycling: lives
Life span is 120 days.
Erythropoiesis: primary sites of erythropoiesis
Liver and spleen are primary sites of erythropoiesis between 2 - 5 months of gestation.
Erythroblasts: Normoblast
Looses nucleus
Red Blood Cell Recycling: when replaced
Loss of biconcave shape leads to removal by the reticular endothelial system.
who RBC Recycling
Macrophages of liver, spleen & bone marrow monitor RBC condition. Remove worn out RBCs before they break (hemolyze) That way, Hb can be recycled
Mature mammalian RBCs lack
Mature mammalian RBCs lack organelles—there is no nucleus, mitochondria, RER, or Golgi apparatus.
Red Blood Cell Recycling: how replaced
Meshwork making up the spleen and liver Contains fixed macrophages which detect abnormalities in old RBCs. Destruction of old RBCs is balanced by production of new RBCs in bone marrow.
Sickle-Cell anemia:
Mutation in Hb gene results in a single amino acid substitution in the Hb molecule. Change in shape of RBC severely affects ability to carry oxygen. causes them to get stuck in the capillary beds.
Red Blood Cell Recycling: mature RBC structure
No organelles Few cellular proteins other than hemoglobin No mechanism for repair - Only last in the circulation 120 days Low energy demands - Anaerobic respiration
Aplastic anemia
Normal red marrow becomes dysfunctional: Drugs, cancer, toxins, radiation, chemotherapy Severe cases treated by bone marrow transplant.
how much RBC in human
There are about 14-16.5 g Hb/100 ml of blood in males, and about 12-15 g Hb/100 ml in females.
Pernicious anemia causes
Therefore, causes of pernicious anemia result from either: Vitamin B12 deficiency, Inability of the parietal cells in the stomach to produce intrinsic factor. Inability of the intestine to absorb intrinsic factor bound to vitamin B12
Hb carry O2
Therefore, each Hb molecule can potentially carry 4 oxygen atoms and there are about 280 million Hb molecules/RBC.
RBC n ATP
They generate ATP anaerobically, so they do not consume any of the oxygen they carry to the tissues.
RBC carry O2
This means that each RBC can carry about 1,000,000,000 (1 billion) molecules of oxygen.
erythropoiesis is controlled and depends on:
To maintain homeostasis, erythropoiesis is controlled hormonally and depends on: Adequate dietary iron, amino acids, and certain B-vitamins, Intrinsic factor produced by the stomach gastric glands.
Anemia: def
Too few RBCs or too little hemoglobin/RBC
Too few erythrocytes
Too few erythrocytes leads to tissue hypoxia (oxygen deprivation).
Too many erythrocytes
Too many erythrocytes makes the blood too viscous or too many erythrocytes decreases erythropoietin production.
Hemocytoblast:main lines
Two main lines: Lymphoid stem cells which gives rise to the lymphocytes, myeloid stem cell which gives rise to monocyte, granulocyte colony forming cells.
Vitamin B-12 fn
Vitamin B-12 is needed for the production of hemoglobin.
structure fn
binconcave 1. makes them flexible yet strong so they can squeeze through capillaries. 2. increases surface area for diffusion of oxygen. 3. The large surface to volume ratio of the biconcave shape provides 30% more surface area than comparably sized spherical cells. 4. In addition, it enables RBCs to "stack" which smoothes blood flow through tissues, and 5. permits RBCs to bend and flex when entering capillaries smaller in diameter than the RBCs.
...What happens to the hematocrit of a dehydrated patient? What happens to the hematocrit of a patient with a chronic ulcer? What happens to blood viscosity and flow through blood vessels under each of these conditions?
dehydrated person: decrease H2O - increase HCT - more viscous ulcer - loose blood - HCT increase - blood less viscous
Carbaminohemoglobin
has picked up CO2 from peripheral tissues. About 20% of the carbon dioxide transported in the blood combines with Hb, but it binds to the amino acids of the globin, not the heme (carbaminohemoglobin).
Nutritional causes:
inadequate dietary iron, vitamin B12.
Pernicious anemia
insufficient RBC production resulting from the stomach not making intrinsic factor which is required for the small intestine to absorb vitamin B12.
Thalassemia
is a hereditary form of hemolytic anemia due to a defect in the synthesis of Hb. Altered shape of RBCs makes them break easily.
jaundice
jaundice results if biliary drainage is blocked. Biliruben builds up in blood and its yellow color is best seen in the whites of eyes.
Red blood cell count: def
number of RBCs/ml of whole blood.
Deoxyhemoglobin
oxygen is not bound to iron & blood appears burgundy in color. In the tissues, oxygen detaches from the iron (deoxyhemoglobin).
Erythrocyte Development: whole thing
Notice that as development proceeds, the erythroblasts gradually become smaller, the nucleus shrinks and becomes very dense, and the cytoplasm turns from blue (indicative of RER involved with the synthesis of hemoglobin) to violet and then reddish as the hemoglobin product accumulates. Eventually, the nucleus becomes pycnotic (dies) and is ejected from the developing cell which is now called a normoblast. The resulting stage is called a reticulocyte because small fragments of the RER remain in the cytoplasm. Usually reticulocytes mature in the bone marrow for a couple of days before entering the circulation, but a small number accounting for about 0.8% of the RBC population are found in the bloodstream under normal circumstances.
Formed Elements list
Erythrocytes (RBCs) Leukocytes (WBCs) Platelets
Structure of Red Blood Cells
Erythrocytes are about 8 mm in diameter and have a biconcave shape
RBC numbers
Erythrocytes or RBCs comprise 99.9% of the formed elements of blood. There are approximately 260 million RBCs in a single drop of blood, and 25 trillion RBCs in bloodstream.
Regulation & Requirements for Erythropoiesis: number of circulating RBC
Number of circulating RBCs is constant. Represents a fine-tuned balance between RBC production and destruction.
Anemia: causes: list
Nutritional causes: Pernicious anemia:
Blood doping
Blood doping (removing a person's blood and then infusing it back into them prior to an athletic event) is dangerous for similar reasons.
RBC fn
Completely dedicated to transporting respiratory gases (oxygen and about 20% of the carbon dioxide generated by cellular metabolism.
EPO administration in a healthy person
EPO administration in a healthy person (Olympic competitors) may raise the hematocrit to 65 or more. Potentially dangerous because of added viscosity of blood creates a greater strain on the heart.
EPO is administered to
EPO is administered to cancer patients undergoing chemotherapy, or to a patient recovering from severe blood loss.
RBC consists
Each red blood cell consists of a plasma membrane containing 280 million hemoglobin (Hb) molecules.
Erythropoiesis: Embryonic RBCs production where
Embryonic RBCs are produced in the yolk sac and appear in the circulation at 3 weeks of gestation.
