BSI 2 Lecture 1: Hematology Flashcards
What is the total body fluid volume?
42 liters
Out of the total body fluid volume, how much is inside the cell (intracellular)?
28 liters
Out of the total body fluid volume, how much is outside the cell?
The remaining 14 liters
What can the 14 liters outside the cell be divided into?
11 liters of interstitial fluid and 3 liters of plasma
Where is plasma contained?
In the cardiovascular system, but it exchanges freely with the extracellular fluid which in turn exchanges with the intracellular fluid
In the breakdown of plasma, what is the major component of plasma?
Phospholipids (280 mg/dl)
Osmotic pressure from proteins is called _______ pressure
Oncotic
What is the most common plasma protein?
Albumin ( 5 g/dl)
What is the function of albumin?
It is responsible for 80% of plasma’s oncotic pressure, preventing excess fluid loss from circulation
Regardless of the route of administration, what are virtually all drugs circulated by?
The plasma
Where are plasma proteins primarily synthesized?
The liver (except for antibodies which are gamma globulins secreted by plasma cells)
Apart from their physical effect (oncotic pressure), what are plasma proteins crucial for?
The transport of certain molecules like steroids hormones. Binding to plasma proteins helps prevent inappropriate metabolism and/or excretion
What type of drug interacts with receptors?
Free
Plasma albumin is the most significant plasma protein due to its concentration. What types of drugs does it usually bind with?
Acidic drugs
What do basic drugs bind to, in the plasma?
Beta-globulin and acid glycoprotein
What happens once the binding is saturated (all binding sites are occupied)?
There is an increase in the amount of free drug
When there is an increase in the amount of free drug, what can happen?
They can compete for binding which can occasionally result in significant drug interactions
What are the general functions of plasma?
1) transport of nutrients for energy
2) growth and repair
3) removal of wastes
4) transport of hormones
5) regulation of body temperature
What are the cellular components of blood?
Red blood cells, white blood cells, and platelets
What are the functions of red blood cells?
To carry oxygen and carbon dioxide
What are the functions of white blood cells?
They are part of the immune system
What are the functions of platelets?
They are involved with hemostasis (prevention of bleeding by blood clotting)
What percentage of total blood volume is plasma?
55%
What is plasma composed of by percentage?
91% water, 7% blood proteins, 2% nutrients
What are the blood proteins?
Fibrinogen, albumin, and globulin
What percentage of total blood volume is made up of cellular components?
45%
What is the buffy coat?
A white section in between the plasma and red blood cells that consists of white blood cells and platelets
How many red blood cells are there, on average, per cubic millimeter?
about 5-6 million
What is a hematocrit?
The ratio of combined RBC, WBC, and platelets cell volume over the total blood volume. (~40% in males, ~36% in females)
What is the proper name for a red blood cell?
Erythrocyte
What is the description of an Erythrocyte?
A biconcave, enucleate, disc; salmon colored; diameter is 6-8 micrometers
How many red blood cells are in a microliter of blood?
4-6 million
How long does it take a red blood cell to develop?
5-7 days
How long is the lifespan of a red blood cell?
100-120 days
What is the proper name for a white blood cell?
A leukocyte
What is the description of a leukocyte?
Spherical, nucleated cells
How many neutrophils are in a cubic millimeter of blood?
3,000-7,000
What is the function of a neutrophil?
To destroy bacteria by phagocytosis
What are the functions of an eosinophil?
To turn of allergic responses and kill parasites
What is the function of a basophil?
To release histamine and other mediators of inflammation
How many lymphocytes are found in a cubic millimeter of blood?
1500-3000
What is the function of a lymphocyte?
To mount an immune response by direct cell attack (T cells) or via antibodies (B cells)
What are the functions of a monocyte?
Phagocytosis; develop into macrophages in tissues
How many platelets are found in a cubic millimeter of blood?
150,000-500,000
How long does it take for platelets to develop?
4-5 days
How long is the lifespan of a platelet?
5-10 days
What are the functions of platelets?
To seal small tears in blood vessels; instrumental in blood clotting
What type of protein is hemoglobin (Hb)?
Heterotetrameric ( 4 subunits composed of 2 different pairs)
What is special about red blood cells that allows them to squeeze through the smallest capillaries?
They are deformable because of a large excess of plasma membranes
How do red blood cells divide?
The can’t. They don’t have a nucleus, mitochondria, or endoplasmic reticulum
How do red blood cells produce ATP?
Glycolysis
Across the lifespan of a human, where are red blood cells produced?
from 8 months to 5 years they are produced in the long bones (tibia and femur). From then on, the long bones become fattier and stop producing, and the membranous bones (rib, sternum, vertebra) start producing them.
When the long bones stop producing red blood cells, what do they start producing?
White blood cells
Does the body produce nucleated red blood cells?
Yes, in the embryo, nucleated red blood cells are produced by the yolk sac. By the middle trimester, the liver, spleen, and lymph nodes are the main source
Where do all blood cells originate from?
Pluripotential hematopoietic stem cells
Describe the colony-forming unit-erythrocyte stage (CFU-E).
This is the point where the cell is committed by differentiation to becoming a red blood cell, and it cannot become any other cell
What controls RBC growth and production?
“growth inducers”. For example, interleukin-3 promotes growth and reproduction of virtually all types of committed cells, others are type specific.
How is differentiation induced?
by “differentiation inducers” which are controlled by factors outside the bone marrow
What is differentiation factor for red blood cells?
Usually decreased oxygen levels
What are the stages of development of a red blood cell?
1) Proerythroblast
2) Basophil erythroblast
3) Polychromatophilic erythroblast
4) Orthochromatic erythroblast
5) Reticulocyte
6) Erythrocytes
What is an important note about the reticulocyte stage?
This is the point at which the nucleus and endoplasmic reticulum have either been ejected or absorbed because they have no further function
How do reticulocytes turn into erythrocytes?
They leave the bone marrow and enter circulation where they mature into erythrocytes
As successive stages occur in the formation of red blood cells, what happens to hemoglobin and the nucleus?
The nucleus gets smaller and smaller while hemoglobin continues to increase
Through what process do reticulocytes leave the bone marrow?
Diapedesis: reticulocytes enter capillaries by squeezing between endothelial cells
Why is the number of red blood cells tightly regulated?
Because you need a sufficient amount for oxygen transport, but if there are too many, it places enormous amounts of stress on the heart
What happens in any condition that decreases the amount of oxygen to the tissues?
Increased red blood cell production
What is anemia?
Decrease in the ability of blood to carry oxygen
What major substance causes increased red blood cell production?
Erythropoietin
Where is 90% of erythropoietin formed?
In the kidneys. The rest is formed in the liver
What is erythropoietin and what secretes it?
It is a hormone secreted by tubular epithelial cells
If there is damage to the kidneys, what happens to erythropoietin?
It doesn’t get created and can result in severe anemia
How does erythropoietin increase red blood cell production?
It stimulates production of proerythroblasts and increases the rate of the maturation process by up to ten times the normal level
What role does vitamin B 12 and Folic acid play in the life cycle of a red blood cell?
Vitamin B 12 and Folic acid increase DNA synthesis, and a deficiency could result in maturation failure. This can lead to the production of abnormal red blood cells called macrocytes
What is a macrocyte?
cells that do not have the correct/strong/deformable shape of a normal red blood cell, and are often fragile with a significantly reduced lifespan
How is hemoglobin synthesized?
1) 2 succinyl-CoA from the Krebs cycle combine with 2 glycines to form a pyrrole molecule
2) 4 pyrrole molecules combine to make protoporphyrin IX
3) An iron ion is added to protoporphyrin IX to make heme
4) Heme is added to a polypeptide globin to for a hemoglobin monomer
How many types of globin variants are there?
4 (alpha, beta, gamma, delta)
What is the most common adult version of Hb?
Hb that contains 2 alpha’s and 2 beta’s
Why and how is fetal hemoglobin different from normal adult hemoglobin?
It has a higher affinity for oxygen so that is can be transported from the mother to the fetus
In high oxygen concentrations how much oxygen binds to hemoglobin?
Each iron ion binds one oxygen molecule; therefore, a completely saturated molecule can hold 4 oxygen molecules
T or F? Higher O2 concentration will cause more O2 to bind to Fe2+
True
Fe2+ is important not only for transporting O2 but many other crucial proteins/enzymes such as __________________
Cytochromes
The total body Fe is ~4-5gm, 65% of this is found where?
65% Bound to Hb
4% in muscle myoglobin
1% in heme-containing proteins
0.1% found in plasma bound to transferrin
30% stored in the liver bound to Ferritin
What is the function of transferrin?
It transfers the Fe from the GI tract to the receptors on the developing erythrocyte membranes., once endocytosed it enters the mitochondria where heme is synthesized. Also, transport carries Fe to the liver to be stored as Ferritin
Lack of transferrin can cause _____ anemia where red blood cells contain decreased amounts of Hb.
Hypochromic
Where does RBC usually rupture/self-destruct?
In the spleen as the squeeze through the “red pulp” reticular mesh
The released Hb is phagocytized by the macrophages of the _______, _______, and _____ cells
spleen, bone marrow, Kupffer
When RBC’s are recycled, what happens to the Fe?
It is released back into the blood bound to transferrin
What is a necessary component in bile for fat digestion?
Bilirubin (converted from recycled porphyrin from Hb in macrophages)
T or F? Anemia due to blood loss may require 3-6 days for full recovery of RBC’s.
False, weeks not days (plasma loss could be replaced in 1-3 days)
Lack of functioning bone marrow caused by x-rays and other forms of radiation etc is called ______
aplastic anemia
Anemia due to lack of absorption of B12 in the GI tract is called _______________
pernicious anemia
Anemia due to lack of absorption of B12 and folic acid in the GI tract is called __________
Sprue
What is hemolytic anemia?
An inherited condition in which the body produces fragile red blood cells that can easily burst resulting in a shorter lifespan
Sickle cell anemia is due to a single _____ _____ change in a specific position in the globin polypeptide chain of Hb.
amino acid
What is erythroblastosis fetalis?
When Rh- mother has a baby with Rh+, where the mother’s antibodies attack the babies RBC’s resulting in a baby with severe anemia.
What is the condition called when too many RBC’s are produced caused by a mutation which allows uncontrolled division of cells like cancer and making blood difficult to pump?
Polycythemia Vera
What are the principal functions of blood?
O2 and CO2 transport, nutrient and waste transport, hormone distribution, temperature regulation.
What protein is required in the GI tract for absorption of Fe and what mechanism is employed?
apotransferrin helping absorption of Fe via signal-mediated endocytosis
What is Iron (Fe) used for besides making Hb?
Cytochromes for both ETC and drug metabolizing enzymes
