3: RBCs, Blood fxns, & Reticuloendothelial System Flashcards
Shape of RBCs allows for what?
enables RBCs to have a large surface area for gas exchange & gives them flexibility when passing thru capillaries.
What is the Erythrocyte structure?
Biconcave discs with 7-8(micrometer) diameter and thickness (2.0-2.2 micrometer)
-Mature RBCs are non-nucleated and have no organelles.
Can mature RBCs reproduce or make proteins?
No, they have a limited capability to make ATP as well (via anaerobic metabolism)
Where is RBCs synthesized?
In RED BONE MARROW ( at a rate of 200 billion per day )
What is the location of red bone marrow?
1) Flat bones (sternum, ribs & cranial bones)
2) Irregular bones (coxal bones, vertebrae, & scapula)
3) Epiphyses of long bones (femur & humerus)
What are the types of bones
1) Irregular
2) flat
3) long
4) short
Where is yellow bone marrow found? What is a unique property of the yellow marrow?
-In the medullary cavity of the diaphysis
***In severe cases of blood loss it can be converted back to RED MARROW to increase blood cell production
In the fetus where is RBCs formed?
In the liver and the spleen (Extra-medullary erythropoiesis)
In adults when does Extramedullary erythropoiesis occur?
In diseases in which the bone marrow becomes destroyed or fibrosed
In children how does RBC formation differ?
Blood cells are actively produced in the marrow cavities of ALL BONES
***By the age of 20 the marrow in the long bones, except for the upper humerus & femur has become inactive.
What are pluripotential or multipotential stem cells?
Uncommitted stem cells that differentiate into one or another type of committed stem cell
What are progenitor or colony forming units?
Committed stem cells that differentiate into various types of blood cells.
What is the function of pluripotential stem cells?
*****Capable of replacing the bone marrow when injected into a host whose own marrow is completely destroyed
(few in number)
What can CFU colony forming (progenitor cells) be changed to?
1) CFU -Meg–> (Megakaryocyte) platelets
2) CFU-GM (Myeloid series) a) neuts b) Eosinophils c) basophils d) monocytes
3) BFU-E–>Red Cells
How do Lymphocyte progenitor (—>B cells, NK cells, & T cells) cells get made?
Pluripotent stem cell
What is Erythropoietin (EPO)?
A erythropoiesis growth factor which is released by the kidney (and to a smaller extent the liver)
What do the RBCs enter the circulation as?
Reticulocytes, which still contain some organelles :)
***They remain the bone marrow or spleen for a few days to mature into erythrocytes
What are the ingredients for making a normal RBC?
1) Amino acids
2) Iron
3) Folic acid
4) Vitamin B12
What is a the development pathway for a RBC?
Hemocytoblast (stem cell)–> Proerythroblast (Commited cell)–> Early erythroblast, late erythroblast, Normoblast, reticulocyte,–> Erythrocyte
How do Reticulocytes appear in staining?
Do to a very slight basophilic staining.
You see some organelles present in the cell
What kind of feedback loop does Erythropoietin production involve?
A NEGATIVE FEEDBACK LOOP
***as the # of RBCs increase, the red cell mass rises, oxygen is delivered more easily to tissues. Kidneys sense this increase in oxygen delivery and EPO levels drop
What happen to RBC production when oxygen levels are low (HYPOXIA)?
EPO levels rise, & RBC production increases until oxygenation return to normal
What is the RBC membrane like?
Like most cell membranes with the lipid bilayer and both INTEGRAL AND PERIPHERAL PROTEINS.
- Has uniquely expressed protein filaments in the cytoskeleton
- **Protein content has only 10-15 major proteins and many minor
What are some examples of Integral proteins
1) Band 3
2) Glycophorins
3) Aquaporin-1
4) GLUT 1
5) Na+/K+ ATPase (pumps)
6) Ion Channels & Exchangers
What is Band 3? Function?
Constitutes about 25 % of total membrane proteins
Fxn: Anion transports. Exchanges bicarb for chloride across the membrane. Provides linkage of lipid bilayer to the memb skeleton
What are Glycophorins?
Negatively charged proteins that reduce the interaction of RBC with one another and with other cells
What is Aquaporin-1 ?
Serves as selective pores for water transport
What is GLUT 1?
Facilitated diffusion of glucose into the cytosol of RBCs
What is the Na/K+ pump
Active transport of Na+ out of the RBC and K+ into the RBC
Ion channels & exchangers
For Na+, K+ and others
What are the functions of Ankyrin, protein 4.1, protein 4.2m and spectrin?
These Peripheral/Cytoskeleton proteins provide the red cell w/ a FLEXIBLE, yet mechanically RESILIENT, and STABLE, membrane.
What can the consequences be if the RBC lacks spectrin or ankyrin?
Hemolysis (increased RBC breakdown)
What is Hereditary spherocytosis?
Disease caused by defects in the red cell proteins
***characterized by the production of RBCs that are sphere-shaped rather than bi-concave disc shaped
Which disease is associated with abnormally small RBCs that lack the central pallor?
Hereditary Spherocytosis
What happens to abnormally shaped RBCs?
They undergo hemolysis and suffer pre-mature destruction
How is O2 in the blood transported?
1) dissolved in plasma (outside RBC 1.5%)
2) bound to hemoglobin ( inside RBC) 98.5%
How is CO2 transported in the blood?
1) Hemoglobin transports 30% of the total amount of CO2 produced by the body this is = CARBAMINOHEMOGLOBIN or carboxyhemoglobin
What is a hemoglobin molecule made up of?
- 4 polypeptide chains with SH (sulfhydryl groups) ***in reduced form!
- Each polypeptide chain contains a HEME RING
- Iron in the reduced state FERROUS (Fe+2) which binds O2
NOTE: adult hemoglobin = alpha 2 beta 2
At PO2 of 40 mmHg (mixed venous blood) and PO2 25mmHg how much of hemoglobin saturated?
- 75% saturated, 3 heme groups on each hemoglobin molecule have O2 bound
- 50% saturated, 2 heme groups of each hemoglobin molecule have O2 bound
Why does Hemoglobin-Oxygen Dissociation curve sigmoid?
Result of the change in affinity of hemoglobin as O2 molecules bind to heme site
**POSITIVE COOPERATIVITY
Note: Flat part of graph = Loading of O2 in the lungs
steep portion= unloading of O2 at the tissues
Does oxygen transport require energy?
No but in order to survive the 90-120 days the red cell requires regular maintenance that relies on energy
What maintenance does the RBC rely on?
1) Red cell membrane integrity
2) Red cell shape
3) Hemoglobin sulfhydryl groups must be maintained in reduced form
4) Iron must be kept in reduced form
5) Iron gradients
When does the RBC take on the spherical abnormal shape?
if there is insuffiencent energy, the red cell cant maintain these functions and it adopts a shape called SPHEROCYTE
What is the main source of energy for the RBC? What does Erythrocyte metabolism depend on ?
GLUCOSE is source of energy
***Depends EXCLUSIVELY on CYTOSOLIC PROTEINS
What are the 3 important products of glucose metabolism?
1) ATP (main source of energy fo maintaing ion gradients)
2) NADH (required to maintain hemoglobin’s iron in the ferrous reduced state (Fe2+)
3) NADPH (required to maintain GLUTATHIONE on the red cell membrane in its reduced form; reduced glutathione essential for maintaining normal red cell structure and norm Hgb )
How much energy does one molecule of glucose generate in Glycolysis?
What % of glucose is metabolized in this fashion?
2 ATP and 2 NADH
*** 90%
What is the Pentose Phosphate Pathway?
What % of metabolism is generated here?
- Also called Hexose Monophosphate Shut
- Generates NADPH–> RBC energy
***10% of glucose is metabolized by RBCS in this fashion
What is the Pentose Phosphate Pathway linked to Glycolysis through?
Glucose 6- Phosphate
Note:
- if it is oxidized it enters the pentose phosphate pathway!
- If it is isomersized to Fructose-6-phosphate it goes through Glycolysis
What is the waste product of RBCs degradation?
BILIRUBIN
What is reutilized during RBC degradation?
What is transported in plasma bound to albumin?
The Iron and Globin
Bilirubin is bound to albumin
Where is the Spleen located? What is the removal of it called?
Located in LUQ; often injured
Splenectomy= removal
RBCs shrink or swell with an osmotic pressure greater than that of normal plasma?
In hyperosmotic solution RBCs shrink!
RBCs shrink or swell with an osmotic pressure LESS than that of normal plasma?
In hypotonic solution RBCs SWELL up and undergo hemolysis (Loose their hemoglobin)
What happens to the hemoglobin of hemolyzed red cells ?
Dissolves in the plasma, coloring it red
What % solution is isotonic with plasma ?
0.9% NaCl solution
How can H+ ions affect extracellular fluid?
- RBC operate at a certain pH and healthy individuals make 50-100 mEw/L of H+ a day via basic metabolic rxns
- Body is sensitive to pH changes
How is pH (H+ ) controlled in the RBC, LUNGS, and KIDNEYS
RBC: Converts the Co2 w/ Carbonic anhydrase into a bicarb product
LUNGS: Controls it by adjusting respiration rate and depth
KIDNEYS: Can excrete H+ in urine when low pH is sensed
What are the 3 major chemical buffer systems in the blood?
1) Carbonic acid -bicarbonate (can soak up and relese H+ when needed)
2) Phosphate (can soak up and relese H+ when needed)
3) Protein (Hemoglobin, albumins)
- Amine portion Soaks H+ if excess H+ is present (acidosis)
- Carboxyl portion releases H+ (alkalosis ) if shortage of H+
How does the Blood regulate the Temperature in cold temps?
Cold temperatures —>stimulate SNS fibers–> Vascular smooth muscle of skin blood vessels (alpha 1 mediated) –>VASOCONSTRICTION causes decrease in blood flow to surface of skin –>reduces heat LOSS
How does the Blood regulate the Temperature in warm temps?
Warm temps–>inhibit SNS fibers–>Vascular smooth muscle of skin blood vessels (alpha 1 mediated)– VASODILATION (causes increase in blood flow to surface of skin) –> Warm blood from the body core is SHUNTED to the body surface; heat is then lost by radiation & convection
What does shunting of blood to the surface cause ?
It is evidenced by redness and warmth of the skin :)
