Exam #2: Physiology of Blood Flashcards
Describe the composition of blood, both generally & specifically.
Generally, blood is 7-8% of total body weight & on average there are ~5 L of blood in the human body.
Specifically, roughly 42% of blood is composed of the formed elements, 58% is plasma, and there is a small fraction called the buffy coat.
What is the buffy coat?
WBCs
Platelets
Describe the general composition of plasma.
Plasma is 92% water; the remaining 8% is composed of: - Proteins
- Other solutes
What are the proteins in plasma?
Albumin
Globulin
Fibrinogen
Regulatory proteins
What are the other solutes?
Ions/ electrolytes
Nutrients
Respiratory gases
Waste products
What are the formed elements in blood?
RBCs
Platelets
WBCs
List the WBCs & identify their relative abundance.
Neutrophils (60-70%) Basophils (0.5 - 1%) Eosinophils (2-4%) Monocytes (3-8%) Lymphocytes (25-33%)
What is the difference between plasma and serum?
Serum is plasma without fibrinogen & other clotting factors
What are the major positive charges in plasma? Which are routinely measured?
*Na+
*K+
Mg++
Ca++
Only Na+ & K+ are routinely measured in blood tests.
What is a miliequivalent?
A mole of a substance multiplied by the charge of that substance.
What is the major negative charges in plasma? Which of these are routinely measured in blood tests?
Albumin *Cl- *HCO3- HPO4- SO2-- Lactate Citrate
Cl- & HCO3- are routinely measured in blood tests.
What is an anion gap? What is a normal anion gap?
The concentration & charge of the measured cations is larger than the concentration & charge of anions. This difference is referred to as the anion gap.
A normal anion gap is 8-16 mEq/L
*Note that the anion gap represents the unmeasured anions
How is anion gap used clinically?
Increased anion gap is used in the diagnosis of metabolic acidosis because of:
- Increases in unmeasured organic anions (e.g. ketoacids)
- Decreased bicarbonate (HCO3-) that builds to elevated H+ during acidosis
BOTH increase the anion gap b/c bicarbonate is a measured anion
How does hypoalbuminemia affect the anion gap?
Hypoalbuminemia decreases in anion gap. Why?
- Albumin is an unmeasured anion
- Decreased levels of albumin lead to compensatory retention of the measured anions (HCO3- & Cl-)
- A higher measured concentration of anions= lower anion gap
What is an osmole?
Moles of solute times the number of ions or particles upon its dissociation in solution
E.g. 1 mmol/L NaCl= 2mOsm/L (Na+ & Cl- = x2)
What is the osmolality equation?
Osmoles of solute/kg solvent
What is the normal reference range for the osmolality of blood?
292.6 mOsm/Kg H20
How does the osmolality of the plasma compared to the osmolality of the interstitial fluid? What is the net effect of this difference?
The osmolality of plasma is higher than the osmolality of the interstitial fluid because albumin is too large to cross the capillary membrane. This difference drives water into the vasculature
What is albumin? What are the functions of albumin?
- Albumin is a plasma protein (anion, most abundant–58%–plasma protein)
- Responsible for 70-80% of colloid osmotic pressure, or oncotic pressure, that drive water into the vasculature
- Transporter in the blood (important for drugs)
Clinically, what does hypoalbuminemia lead to?
Edema
- Note that the causes of hypoalbuminemia are generally three-fold:
1) Decreased synthesis
2) Increased volume distribution
3) Increased excretion & degradation
What are the important globulin proteins in plasma?
Gamma-globulin
Transferrin
Haptoglobin
What is the function of gamma-globin?
Gamma-globulins are antibodies involved in immunity
What is the function of Transferrin?
Transferrin binds iron to allow for iron transport to the bone marrow for erythropoesis
Note that free iron in the circulation is TOXIC.
What is the function of Haptoglobin?
- Haptoglobin binds free Hemoglobin that enters the plasma following intravascular hemolysis (lysis of RBCs)
- Haptoglobin then transports Hemoglobin to the liver & spleen, where the complex undergoes endocytosis by macrophages
- Within macrophages, heme is degraded, and iron & amino acids are recycled
What is the diagnostic utility of Haptoglobin concentrations?
Diminished Haptoglobin concentrations are indicative of Intravascular hemolysis as more Haptoglobin binds Hemoglobin (& has a short half-life), leaving less free Haptoglobin in the plasma
What would happen to plasma hemoglobin and haptoglobin levels during an episode of increased intravascular hemolysis? What would be expected to show an increase in plasma concentration in response to intravascular hemolysis?
- Decrease
- Increased lactate dehydrogenase levels in the serum
What is a blood film or peripheral blood smear used for?
Generally, this is a qualitative test used for:
- Estimation of abundance of cells
- Size of RBCs (nutrient deficiencies)
- Estimation of Hb content
- WBCs
What is hematopoesis? Where does hematopoesis occur?
Hematopoesis is the process by which all blood cells are formed. It occurs in different locations throughout life.
- Prenatally= yolk sac, then spleen & liver
- Postnatally= bone marrow ONLY
Splenic hematopoesis as an adult is ABNORMAL
Describe the general pathway of hematopoesis. Draw the pathway.
1) Hematopoietic stem cell (HSC) divides into 2x daughter cells: 1 HSC & 1 Colony forming unit
2) Lymphoid progenitor cell line or Myeloid progenitor cells line (called “Colony forming units”)
What cells are derived from the Lymphoid lineage?
T cells
B cells
NK cells
What cells are derived from the Myeloid lineage?
- Erythrocytes
- Platelets & Megakaryocytes
- Neutrophils
- Eosinophils
- Basophils
What regulates hematopeosis?
Growth factors i.e. cytokines that operate in combination fashion
What are the important characteristics of RBCs? Include both shape & important enzymes.
- Biconcave
- No nucleus
- No organelles (mitochondria)
Contain significant lactate dehydrogenase & carbonic anhydrase
What is important about the shape of the RBC?
The biconcave shape of the RBC:
- Increases the SA/V ratio
- Makes RBCs easily deformable, which is necessary for passage through the narrow vessels of the spleen
*Note that aging of RBC makes them less deformable & therefore, more likely to get stuck in the spleen–>recycling
What is the primary type of Hb in adults?
Type A (HbA)
Describe the structure of Hb.
Hemoglobin contains 4 globin chains:
- 2x alpha globin chains
- 2x beta globin chains
Each is bound to a heme moiety containing iron (binding site for oxygen)(
What is anemia?
Too few erythrocytes (low hematocrit)
Can be caused by:
- hypo-proliferative diseases of the bone marrow
- Nutrient deficiencies
- Hemolysis
- Bleeding
- Overhydration
What is polycythemia?
Too many erythrocytes
Can be caused by:
- proliferative diseases of the bone marrow
- Disease states that reduce oxygen levels
- Dehydration
What is erythropoesis? Outline the process of erythropoesis.
Erythropoesis is the production of red blood cells, which must be tightly regulated to prevent anemia & polycythemia.
1) HSC–>Myeloid progenitor
2) Myeloid progenitor–> Erythroid progenitor
3) Erythroid progenitor–>erythroblast
4) Erythroblast–>reticulocyte
5) Reticulocyte–> mature erythrocyte
What is the function of erythropoietin (EPO)?
Erythroid progenitors, produced from myeloid progenitors, express an EPO receptor; EPO binding to its receptor is REQUIRED for continued RBC differentiation
What is a reticulocyte?
Immature RBC with no nucleus
*However, the reticulocyte does contain some organelles that are NOT found in the mature RBC
How is EPO produced?
The kidney senses oxygen levels & produces EPO when O2 levels decrease
Note that chronic renal failure can REDUCE the amount of EPO produced; thus, decreasing erythrocyte production, leading to anemia
What factors cause an increase in EPO production?
EPO is produced in response to low oxygen levels (sensed at the kidney). Factors that may lead to low oxygen include:
1) Low blood volume
2) Anemia
3) Impaired Hb function
4) Poor blood flow
5) Pulmonary disease
What is hematocrit? What is a normal hematocrit?
A percentage: volume RBCs/ Total Blood Volume
- Male normal= 40-54%
- Female normal= 36-48%
How are levels of oxygen detected? What is the effect on EPO when oxygen levels are low?
Hypoxia inducible factor 1alpha (HIF-1a) facilitates EPO transcription
- HIF-1a is continuously transcribed & translated under normal oxygen saturations, & then DEGRADED
- In hypoxic conditions, HIF-1a is NOT degraded & leads to an increase in EPO production
Specifically, HIF-1a is degraded via an intermediate, VHL (von Hippel Lindau protein). In normal circumstances, a protein hydroxylates a proline residue in HIF-1a, VHL then ubiquinates HIF-1a, & it is degraded. In hypoxic conditions, the protein that hydoxylayes, no longer functions.
What is Chuvash polycythemia, or congenital polycythemia?
Polycythemia caused by a mutation in VHL; VHL is no longer able to ubiquinate HIF-1a, thus EPO is constantly produced (leading to RBC production)
How are erythrocytes broken down?
1) Intravasular hemolysis= lysis in circulation (Haptoglobin)
2) Extravascular hemolysis= phagocytosis by macrophages in the spleen or liver
Describe the process of extravascular hemolysis.
In the macrophage, Hb is degraded into iron & heme.
Iron:
1) Iron binds transferrin
2) Transferrin/iron complex is transported to the liver, where iron is recycled.
Heme:
1) Heme is converted to bilirubin, attached to albumin, and transported to the liver as well.
2) Bilirubin is conjugated & excreted into the bile.
3) Bile enters the intestines. In the intestine, conjugated bilirubin is:
a. Converted to stercobilin & excreted in feces
b. Converted to urobilinogen, reabsorbed in blood, and eventually excreted in urine by the kidneys.
How are abnormal elevations in hemolysis manifested?
Increase urine urobilinogen
What causes jaundice?
Increased tissue deposition of bilirubin
What is the function of platelets?
Hemostasis or the cessation of bleeding
How & why are platelets activated? Describe what happens after platelet activation.
- Injury exposes collagen (& other factors), that activate platelets when they come in contact.
- Morphological change occurs following collagen contact & platelets:
a. Form a blood clot (plug)
b. Secrete clotting factors (e.g. Factor V)
Define thrombocytosis.
Too many platelets
Define thrombocytopenia.
Too few platelets
Outline the process of thrombopoesis.
1) Megakaryocyte-progenitor cells differentiate into megakaryocyte precursors, via thrombopoietin (TPO), which is secreted constitutively via the liver & bone marrow
2) Megakaryocyte precursors undergo endomitosis, causing them to become large multi-nucleated cells
3) Platelets are produced via cytoplasmic budding
4) Platelets contain TPO receptors, which lessens the stimulus for the production of further platelets
