3 - Blood Physiology Flashcards
RBCs can concentrate hemoglobin in the cell fluid up to:
34g/100ml of CELLS
This is the metabolic limit of the cell’s hemoglobin-forming mechanism
In normal people, the percentage of hemoglobin is almost always:
the maximum percentage (34% of cells, which equates to 14-15g/dL)
How does hemoglobin circulate in humans?
INSIDE RBCs (not bound to the outside)
How much oxygen can be carried by hemoglobin in 100ml of blood?
Each g of Hgb can bind with 1.34ml O2, which means
19-20ml O2/100ml blood
Where are RBCs produced in utero? After birth?
Liver
Bone Marrow
When do long bones stop producing RBCs?
Around 20 years old
RBCs in adults are produced in which bones?
membranous bones: vertebrae, ribs, sternum, ilia
All cells in circulating blood are derived from which cell?
multipotential hematopoetic stem cell
How is the supply of multipotential hematopoetic stem cells maintained?
Every time one is triggered to reproduce, it produces another stem cell in addition to the other cells it multiplies into
Which growth inducer promotes growth and reproduction of virtually all the different types of committed stem cells?
Interleukin-3
What differentiates a reticulocyte from a full grown erythrocyte?
still contains a small amount of basophilic material (remnants of unnecessary organelles)
These organelles disappear over 1-2 days
The principal stimulus for RBC production in a low oxygen state is:
circulating erythropoietin
On a cellular level, how do the kidneys trigger RBC production in hypoxemic states?
Renal tissue hypoxia leads to high levels of Hypoxia-Inducible Factor 1 (HIF-1)
HIF-1 is a transcription factor, increasing transcription and production of erythropoietin
If erythropoietin is produced in the kidneys, why do RBC levels increase if other parts of the body are hypoxemic, even if the kidneys are not?
Somehow other tissues are able to send signals to the kidney
Circulating NE, Epi, and prostaglandins also stimulate erythropoietin
If someone’s kidneys are both removed or dead, how much erythropoietin can they make?
About 10% of normal, which is the percentage usually made by the liver
In hypoxic states, erythropoietin is produced within minutes. How long does it take for new RBCs to appear?
About 5 days
Erythropoietin stimulates growth, but it also increases the RATE of RBC production
Which two vitamins are essential to the final maturation of RBCs?
Why?
Vitamin B12 and Folic Acid
Required for formation of thymidine triphosphate, which is a building block of DNA
What are the characteristics of blood cells formed with deficient Vitamin B12 and/or Folic Acid?
Large RBCs (macrocytes)
flimsy membranes
Irregular shapes
they can carry oxygen, but have live about half or 1/3 as long d/t fragility
Vit B12/Folic Acid deficit anemia is called:
maturation failure anemia
Why is intrinsic factor necessary for B12 absorption?
Binds tightly with B12, and the binding protects from digestion by secretions
IF ferries it to the brush border and transports it into the blood via pinocytosis
Where is B12 stored?
Liver
Released in response to bone marrow levels
How long does abnormal B12 absorption have to take place to cause anemia?
Takes about 3-4 years to work through all the B12 stored in the liver
Besides deficient intrinsic factor, what else can cause B12/folic acid deficiency?
Any sort of malabsorption syndrome (sprue)
The most common form of hemoglobin in adults is:
Hemoglobin A
Every hemoglobin molecule is comprised of:
Four heme prosthetic groups
Four hemoglobin chains
Every molecule of hemoglobin can carry _____ atoms and _____ molecules of oxygen
8
4
On a cellular level, what causes sickle cell anemia?
One of the amino acids on the hemoglobin’s beta chains is substituted
When it’s exposed to low oxygen, it forms elongated crystals inside the RBC, making it almost impossible for the cell to pass through tiny capillaries
Moreover, the crystals can rupture the cell membrane, leading to hemolysis
Why does O2 dissociate so easily from hemoglobin?
It binds very loosely with the iron atom via a coordination bond
the oxygen doesn’t become ionic when it’s bound, it remains a molecule
What percentage of iron in the body exists as hemoglobin?
65%
What is hypochromic anemia?
RBCs with much less hemoglobin than normal
When there is more iron in the body than can be stored as ferritin, what happens?
It is stored in the cells as hemosiderin
Unlike ferritin, hemosiderin forms large clusters inside the cell and can be seen on a microscope
Describe the process of iron absorption:
- liver secretes apotransferrin into bile
- apotransferrin binds with free iron and iron compounds in the gut, forming transferrin
- Transferrin binds to receptors in intestinal epithelial cells
- Released into the blood stream as plasma transferrin
How quickly does iron absorption occur?
Extremely slowly
Maximum rate of a couple mg per day
You can’t fix an iron deficiency quickly with diet
Which organelles do RBCs have?
They DON’T have a nucleus, mitochondria, or ER
The do have cytoplasmic enzymes that can metabolize glucose and form small amounts of ATP
Which cells are responsible for breaking down hemoglobin?
Macrophages in the intestines (Kupffer cells), spleen, and bone marrow
What is anemia?
What are the two broad causes?
A deficiency of hemoglobin in the blood
can be caused by too few RBCs or too little Hgb within those RBCs
After a hemorrhage, how long does it take for plasma cells to replenish? RBCs?
1-3 days
3-6 weeks
Why does chronic blood loss result in microcytic hypochromic anemia?
The body can’t absorb enough iron from the intestines to form Hgb as rapidly as it’s being depleted, so the RBCs are smaller and contain less Hgb
What causes aplastic anemia?
Bone marrow aplasia of some kind.
Idiopathic in 50% of cases
Other causes: radiation, toxic chemicals, lupus (immune system attacks bone marrow stem cells)
What is megaloblastic anemia?
What causes it?
Large RBCs with odd shapes
pernicious anemia, total gastrectomy, intestinal sprue
What is hemolytic anemia?
fragile RBCs with short life spans that are destroyed faster than they can be formed
What is hereditary spherocytosis?
RBCs are small and spherical, can’t withstand any compression (get ruptured in the spleen)
Sickle cell anemia is caused by an abnormal types of Hgb called:
Hgb S
What is erythroblastosis fetalis?
Rh-positive RBCs in fetus attacked by antibodies from Rh-negative mother
What is secondary polycythemia?
Increased RBCs in response to hypoxia
Can either be caused by pathological causes or living at a higher elevation
What is polycythemia vera?
blast cells don’t stop producing RBCs even when too many cells are already present
Usually causes excess amounts of platelets and WBCs too
How is cardiac output effected in polycythemia vera?
blood viscosity decreases preload, and increased blood volume increases preload
The two pretty much neutralize each other, and CO is often normal
What are the two types of antigens involved in blood typing?
The ABO system and the Rh system
What are agglutinogens?
Which ones are found on human RBCs?
antigens that cause RBC agglutination
A and B antigens
Type O blood contains which agglutinogens?
Neither A nor B
The type O allele is pretty much inert and causes no agglutination
What are the frequencies of the blood types?
O: 47%
A: 41%
B: 9%
AB: 3%
What are agglutinins?
IgG and IgM immunoglobulins
when type A agglutinogen is NOT PRESENT in the RBCs, they develop anti-A agglutinins
Why do agglutinins cause clumping?
When anti-A agglutinins are mixed with blood that contains A agglutinogens, the agglutinins attach themselves to the RBCs
BUT the agglutinins have multiple binding sites, so they attach multiple RBCs, and clumps form
In blood transfusion reactions, what mediates acute hemolysis?
Delayed hemolysis?
Acute: activation of the complement system and formation of membrane attack complexes
Delayed: clumping due to agglutination
Is immediate or delayed hemolysis more common?
Delayed
What factors must align for an immediate hemolysis to occur with a blood transfusion?
A very high titer of antibodies
different types of antibodies, primarily IgM, called hemolysins
How many Rh antigens are there?
Which one is most prevalent?
6
D
Someone who is called “Rh Negative” does not have ______
type D Rh antigen
What skin color has the highest rate of Rh negative?
Whites! 85% Rh positive
Everyone else is over 95%
How long does it take to form Anti-Rh agglutinins?
2-4 months
In most cases of erythroblastosis fetalis, the mother is Rh ____ and the father is Rh _____
negative
positive
How can erythroblastosis fetalis be treated?
Infusing Rh-negative blood to the infant while removing Rh -positive blood
By the time the infant produces its own Rh-positive blood cells again, the mother’s macrophages are dead
Why do neonates who survive erythroblastosis fetalis often have brain damage?
Kernicterus
How does Rhogam work?
Binds to the D antigen on the fetus, preventing detection by maternal macrophages
Somehow inhibits B lymphocyte antibody production in the expectant mother
Why do hemolytic transfusion reactions cause kidney failure?
- toxins released from hemolysis cause renal vasoconstriction
- decreased RBCs + toxins = circulatory shock and decreased RBF
- if free hemoglobin is greater than the amount of haptoglobin, the rest leaks into the glomerular membranes and clogs up the tubules
Define:
Autograft
Isograft
Allograft
Xenograft
Auto: from same person
Iso: from identical twin
Allo: from one person to another
Xeno: from nonhuman animal to human
What is the difference between serum and plasma?
Serum is plasma that has been allowed to clot in the lab to remove fibrinogen and other clotting factors
Where are immunoglobulins produced?
by plasma cells in the lymph nodes and other lymphoid tissues
The other name for platelets is:
thrombocytes
Why do RBCs have such a limited lifespan?
They can’t undergo mitosis
WBCs are categorized by structure into ___ or _____
And by function into ____ or _____
granulocytes or agranulocytes
phagocytes or immunocytes
What gives granulocytes their name?
Contain membrane-bound granules with digestive enzymes and inflammatory mediators
How are granulocytes transported to sites of injury?
They move themselves, like amoebas!!
Called diapedesis
What is the most numerous granulocyte?
Neutrophil
60% of WBCs
Once neutrophils are activated, how long do they live?
1-2 days
Their death (and release of granules) causes debridement
List the four granulocytes:
Neutrophils
Eosinophils
Basophils
Mast cells
Describe the granular actions of the four granulocytes (what do they eat/produce?)
Neutrophils - digestive enzymes for large microorganisms/debris
Eosinophils - digestive enzymes for antigen-antibody complexes and viruses
Basophils - chemical mediators and anticoagulant (think IgE)
Mast cells - chemical mediators (particularly vasoconstriction)
What are the three agranulocytes?
monocytes
macrophages
lymphocytes
_____ and ____ make up the mononuclear phagocyte system
monocytes
macrophages
What is the difference between monocytes and macrophages?
Monocytes are immature or undifferentiated macrophages
Platelets have a _____ cell type
They really aren’t cells!
Just irregularly shaped cytoplasmic fragments that help with coagulation
What are the primary lymphoid organs?
Thymus and bone marrow
What are the secondary lymphoid organs?
spleen, lymph nodes, tonsils, peyer patches
What are the sequelae of spleen removal?
- Leukocytosis
- increased circulating iron
- Diminished IgM response
- Increased # of defective RBCs and platelets
- Thrombocytosis, thrombosis
______ are the primary site for the first encounter between antigens and lymphocytes
lymph nodes
How do lymphocytes get into lymph nodes?
diapedesis across the epithelial membrane!
The typical human requires ______ new blood cells each day
100 billion!
Where does hematopoiesis occur in adults? In a fetus?
bone marrow
liver and spleen
____ and ____ mature differentiate fully before entering the blood
____ and ____ continue to mature in the blood and secondary lymph organs
erythrocytes and granulocytes
monocytes and lymphocytes
What is extramedullary hematopoiesis?
blood cell production in tissues other than the bone marrow
Which cytokines stimulate hematopoiesis?
Colony-stimulating factors
What are the two pools of hematopoiesis?
the stem cell pool (maintains the number of pluripotent stem cells)
The bone marrow pool (cells that are actively proliferating and maturing)
What is the marginating storage pool?
In blood vessels, neutrophils are stored by adhering to the endothelium until needed for an inflammatory response
What is the most significant side effect of exogenous r-HuEPO?
Hypertension
_____ iron can bind and release oxygen. ____ Iron cannot
Fe2+ (Ferrous)
Fe3+ (Ferric)
What is deoxyhemoglobin and oxyhemoglobin?
Binding of oxygen to ferrous iron creates oxyhemoglobin
Release of oxygen reduces iron back to ferrous iron (deoxyhemoglobin)
What is methemoglobin?
Why is it problematic?
Hemoglobin whose iron has not been reduced
In order for oxyhemoglobin to once again become deoxyhemoglobin (which can bind with oxygen), the ferric iron (Fe3+) has to be reduced back to ferrous iron (Fe2+) by methemoglobin reductase
Methemoglobin cannot bind with O2
Which is more common: folate deficiency or Vit B12 deficiency?
Folate
the body only contains a couple months’ worth of folate, vs years of B12
