ANP 1105 Blood Part 1
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Transcript of ANP 1105 Blood Part 1
Topic #4
Blood
Joanna Komorowski, Ph.D.
Part 1
Learning objectivesMarieb and Hoehn 8th ed.
• 4.1.1 Describe the composition of blood (pp. 634-637)
• 4.1.2 Erythrocytes: describe their structure, function & life cycle (pp. 637-643)
The major components of whole blood
Blood is a specialized type of connective tissueIt contains:- living blood cells called formed elements - nonliving blood plasma
• Blood is slightly alkaline (pH = 7.35-7.45• Its temperature = ~ 38C (somewhat higher than body temp.)• 8% body weight (5-6 L ♂; 4-5 L ♀)
Functions of blood• Transport (distribution):
- O2, nutrients
- CO2, metabolites, nitrogenous waste products
- hormones
• Regulation:
- body temperature
- pH
- fluid volume
• Protection:
- prevention of blood loss
- prevention of infections (antibodies, complement proteins)
BloodBlood plasma• 90% water• Contains solutes: nutrients, respiratory gases,
hormones, electrolytes, proteins (albumin, globulins), and wastes (e.g., by-products of protein breakdown)
Formed elements• Erythrocytes, leukocytes, and platelets• Erythrocytes and platelets do not divide!!
Figure 17.3
Erythrocytes
Structure & basic characteristics• Small biconcave cells that lack nucleus and organelles• Contain protein spectrin that helps RBC to be flexible, change shape, and squeeze through narrow
capillaries• Huge surface area for gas exchange• High hemoglobin content• Anaerobic metabolism sparing O2 consumption
Hemoglobin (Hb)
• Hemoglobin is made up of four protein globin subunits, each bound to the iron binding red heme pigment
• Each iron atom can combine reversibly with one molecule of oxygen (4 per Hb molecule; each RBC contains 250 million Hb molecules!!)
• Each globin molecule is made of 2 and 2 polypeptide subunits• Hemoglobin carrying O2 = oxyhemoglobin• Hemoglobin carrying CO2 = carbaminohemoglobin• O2 combines with heme group, but CO2 combines with globin part
RBC standard values
Mattson Porth Essentials of Pathophysiology 2007
Red Blood Cell production = hematopoiesis = hemopoiesis
Red blood cells are continuously renewed by division of cells in red bone marrow (reticular connective tissue bordering on large capillaries called blood sinusoids)
The production of RBCs requires:• Functional hematopoietic stem cells (pleuripotent, at this stage can
develop to any blood cell type)• Erythropoietin• Iron
• Folate
• Vitamin B12
Red Cell Production
Stem cells
Erythroblasts
Reticulocytes
Red blood cells
Erythropoietin
Life span of RBC is 100-120 days
Erythropoesis
The appearance of the membrane surface receptors for specific growth factors and hormones that “push” the celltowards specialization
Fig. 17.5
15 days
RBC development
Mattson Porth Essentials of Pathophysiology 2007
Erythropoetin (EPO) mechanism for regulating erythrocytes
• When cell O2 falls, oxygen “sensor” in kidney and liver (a heme protein) stimulates transcription of EPO
• Kidney produces 85%-90% of EPO
• Other stimulators of EPO- Catecholamines- Androgens- Alkalosis
EPO production can result from: • blood content, e.g., hemorrhage• Insufficient Hb per RBC• O2 availability
Athletes & EPO abuse: can increase hematocrit from 45% to 65%; BUT increased viscosity plus dehydration during race can clotting, stroke, heart failure
Life cycle of RBC
•Most hemoglobin degradation – in the macrophages of the spleen
•Iron is reused
• Heme is reduced to bilirubin and eventually converted to urobilinogen metabolised by bacteria to stercobillin an excreted in feces
Iron uptake, incorporation into hemoglobin and
storage
Iron is transported by transferrin and stored inside cells as protein-iron complex ferritin and hemosiderin
Iron uptake, incorporation into hemoglobin and storage
The most common areas of iron storage in our bodies: liver, bone marrow, intestinal mucosa and spleen
If the body does not need iron, it is stored in the mucosal cells and lost when these cells die and are slough
Cofactors for RBC Production
• Dietary iron:– Heme iron is better absorbed than non-heme
iron
• Vitamin B12 and folate
– Vitamin B12 and folate are necessary for synthesis of nucleic acids and nuclear maturation of the RBC
– Vitamin B12 requires intrinsic factor for effective absorption
Iron• Found in every living cell
• Occurs in foods in various forms
• Heme iron (in hemoglobin and myoglobin) is found in:
- organ meats (liver, heart, kidney)
- red meet (beef, pork, veal, lamb)
- fish (clams, oysters, sardines)
- poultry
Iron, cont.
• Non-heme iron (all iron found in vegetables, grains and supplements):- legumes, dry fruits, enriched cereals and pasta- dark green leafy vegetables, eggs
There is more iron in meat than in plant foods!!
Heme iron is absorbed more readily!!!
Iron in foods
Sizer & Whitney, Nutrition Concepts & Controversies, West/Wadsworth, 1997
Practical Dietary Strategies to Meet Iron Needs
• Eat hem rich foods (red meats, shellfish, liver)
• Enhance the absorption of non-hem iron by including vitamin C at the same meal
• Be aware that some foods interfere with non-hem iron absorption (excess bran, strongly brewed tea, oregano)
• Only take iron supplements at the advice of a dietitian or physician•Cook foods in black cast iron pots and pans
Folate deficiency anemia
• Folate, from Latin “folium” meaning leaf
• Involved in metabolism of DNA, amino acids and their derivatives
• Often works together with vitamins B12 and B6 and produces deficiency syndromes often identical to vitamin B12 deficiency
• Folate is necessary for the formation of all new cells including RBC!!!
Folate, cont.• Found mainly in dark green, leafy vegetables,
liver, legumes, fortified cereals• Folate from eggs, dried beans and oranges not as well
absorbed• Milk increases folate absorption!! • Cooking and storage destroy as much
as 50%-90% of folate in foods
• Of all vitamins, most likely to interfere with medications (e.g.,antiacids, aspirine and its relatives, anticonvulsants, oral contraceptives diminish use by the body)
• Recommended dose for adults – 400 microgram/day
Folate deficiency• Folate deficiency can result from:
- insufficient intake and/or absorption (e.g., alcoholism, Crohn’s disease, anorexia, bulimia)
- increased requirements (pregnancy, lactation)
- insufficient utilization due to other factors such as vitamin B-12 deficiency
Megaloblastic anemia caused by folate or vitamin B12 deficiency
Vitamin B12• Vitamin B-12 is required for the production of red blood cells
(it helps in recycling of folate coenzymes), for the maintenance of the sheets surrounding and protecting nerve fibers
• Found mainly in animal products such as meat (especially organ meats), poultry, seafood and eggs but also in fortified cereals and milk
• About 50% of Vitamin B-12 is absorbed by healthy adults
• Pernicious anemia (pernicious means “leading to death”) an autoimmune disorder related to production of the intrinsic factor, needed for transport and absorption of Vitamin B12
Decreased absorption of vitamin B12
• Absorption can be interrupted by:- absence of: R protein, pancreatic proteases, or intrinsic factor produced in the stomach as well as defective binding of the intrinsic factor- absence of much or all of the stomach and ileum- bacterial overgrowth- tapeworm infestation- some ulcer medications (e.g., Omeprazole)- chronic malabsorption (Crohn’s disease, AIDS)
RBC disorders
Anemia Polycythemia
•Deficit of RBC•Low Hb levels•Possible low ferritin levels•Abnormal Hb (Sickle cell anemia, Thallasemia)
•High RBC count•Can be caused by: EPO doping, low atmospheric oxygen, dehydration, etc.
Anemia = the most common disorder of the blood impairment in oxygen availability hypoxia
Anemia
Mattson Porth Essentials of Pathophysiology 2007
General Signs and Symptoms of Anemia
• Increased respiration
• Increased heart rate
• Fatigue
• Decreased activity tolerance
• Pallor
• Murmur
Causes of anemia1. An insufficient number of RBC• Hemorrhagic anemias• Aplastic anemias (destruction or inhibition of red bone
marrow)
2. Low Hb content• Microcytic anemia
- iron deficiency anemia (also vitamin B6 deficit)• Megaloblastic anemia
- folate deficiency
- vitamin B12 deficiency (pernicious anemia)
3. Abnormal hemoglobin• Thallasemias• Sickle cell anemias
RBCs in different types of anemia
Mattson Porth Essentials of Pathophysiology 2007
Vitamin B12 and folate deficiency
Stages of iron deficiency• Two stages of iron deficiency:
1. Depletion of iron stores and iron deficiency without anemia
2. Iron deficiency anemia
Iron deficiency anemia can:- reduce ability to undertake physical activity- cause disturbance in brain metabolism- cause disturbance in muscle metabolism- impair immunity and temperature control
Sports anemia
• Occurs in athletes early in training program, especially after a rest period or injury or after an endurance phase of training
• Is not related to genuine iron deficiency but is mainly due to expanded plasma volume
• The phenomenon is usually transitory• Does not require iron supplements
Assessment of Iron deficiency
• Iron deficiency anemia can be found by performing a hematocrit (% of blood volume occupied by RBC)
- values below 34%-37% suggest
iron deficiency anemia
• Marginal deficiency anemia is not detected by hematocrit so blood ferritin measurements or transferrin receptors measurements are required
- marginal anemia may cause weakness and decreased exercise performance!!!
Hematocrit
Mattson Porth Essentials of Pathophysiology 2007
ThallasemiaThalassemias (Greek ="sea") –underproduction of one of the
globin chains leading to abnormal hemoglobin formation and decreased RBCs survival rates; one of the most frequent inherited disorders worldwide; transmitted in an autosomal recessive fashion
• Two types of thallasemia depending on whether
there is a deficient synthesis of the alpha or beta
globin chains of hemoglobin: alpha-thalassemia
and beta-thalassemia
• Two factors contribute to thalassemia-related anemias:
- Reduction in the synthesis of hemoglobin
- Imbalance in the production of the hemoglobin chains
Thalassemia major
Thalassemia minor
Thallasemia• A person can be heterozygous and have a minor form,
or homozygous with the associated major form of the disease
-talssemia is particularly prelevant in Asian population
• Usually patients with - thalassemia have silent or mild to moderate signs and symptoms (infants with Bart’s – pale, edematous, hepatomegaly, splenomegaly, ascites)
• Diagnosis is confirmed by electrophoresis of hemoglobin
- Thallasemia
Signs and symptoms of - thalssemia:
• skull bone deformities
• Mongoloid faces
• bowing and rarefaction
( bone density) of long bones
• extension of bone marrow into paraspinal and intra-abdominal tumours
• jaundice
• hepatomegaly, splenomegaly,
• cardiac failure, hypogonadism, etc.
- thalssemia is found mainly in people of Mediterranean descent (Greek islands, Italy) but is also found in Middle East and parts of India and Pakistan
Thallasemia treatment and complications
• Treatment:• Blood transfusions• Splenectomy if needed• Iron supplements should be avoided!!!!• Bone marrow transplants
• Iron toxicity in thallasemia major:hemochromatosis = iron overload due to repeated blood transfusions, saturation of iron-binding proteins and of hemosiderin in the liver tissue (can be treated by periodic blood removal or drugs enhancing excretion)
Sickle cell anemia
Sickle-cell anaemia - anemia characterized
by RBC with an abnormal, rigid, sickle shape that decreases the cells' flexibility and results in their restricted movement through blood vessels and restricted delivery of oxygen
• More than 400 variants; large number of those are clinically silent, others give rise to major disorders
• The most common, and most severe form, is the sickle cell anemia, very frequent among Blacks from the sub-Sahara Africa (9-10% are gene carriers)
Mechanism of sickling
Abnormal hemoglobins are characterised by the replacement of an amino acid in one of the chains, secondary to a mutation of a base on the DNA
Sickle-cell anemia
Complications: vascular occlusion, venous thrombosis, arterial emboli, cardiac failure, renal failure, frequent, often serious, even lethal infections (following splenic atrophy), retinopathies (due to microthrombosis), pregnancy accidents
Acute episode of hemolytic or vascular crisis
Signs and symptoms
Sickle-cell anemia treatment• The disease has no widely available cure at the moment
• There are treatments for the symptoms and complications of the disease
• New treatment strategies include bone marrow stem cell transplantations that may offer a cure in some cases; inhalation of nitirous oxide (dilate blood vessels); switching back on fetal hemoglobin production (it does not sickle)
• IMPORTANT: Avoid dehydration, infections, fever, acidosis, hypoxemia and cold exposure
Thalassemia/sickle cells anemia inheritance
Polycythemia
relativepolycythemia, e.g.due to dehydration
Red cell mass
Normal
Increased
secondaryPrimary
(Polycytemia vera)
Polycythemia
Polycythemia – abnormally high content of RBC per unit of blood