HEMATOLOGY

The study of blood and blood-

forming organs Includes study of blood disorders:

Red blood cell disorders
White blood cell disorders Platelet disorders Coagulation problems

FUNCTIONS OF BLOOD
TRANSPORTATION
Blood brings oxygen from the lungs to cells

throughout the body, while taking carbon dioxide to the lungs. It also sends nutrients broken down in the gastrointestinal tract and hormones throughout the body. Blood sends heat and waste products to the lungs, kidneys and skin.

REGULATION supports homeostasis for all bodily

fluids. helps to maintain body temperature, given the heat absorbing and cooling properties of water.

 PROTECTION Blood clotting prevents excess blood

loss due to injury. White blood cells, antibodies and other blood proteins protect against disease.

Physical Characteristics of Blood

Heavier, thicker, and 3-4 X more

viscous than water 38o C (100.4oF) pH : 7.35 7.45 4-6 liters in an adult Varies with electrolyte concentration and amount of adipose tissue

Blood Volume
Blood volume is about 8% of

body weight. 1 kg of blood 1 L of blood 70 kg X 0.08 = 5.6 Kg = 5.6 L 45 % is formed elements 55% plasma

Plasma
92 % Water 8% Solutes organic and inorganic
Plasma proteins largest proportion of

solutes Albumins 58 % of the proteins

maintain osmotic (oncotic) pressure hold water in the blood Globulins 38 % - antibodies synthesized by plasma cells Clotting factors fibrinogen 4 %

Other components of plasma

Nutrients
Hormones Electrolytes

Waste products
Dissolved gases

Formed elements
Three types:

Erythrocytes red blood cells- RBCs Leukocytes white blood cells WBCs Thrombocytes platelets cell fragments

Hemopoiesis (Hematopoiesis)
All blood cells common from a common stem cell Hemocytoblast These are in the bone marrow (red) and develop into blood cells as

needed by the body Mitosis is signaled by biochemicals released from the body Stem cell is signaled to differentiate into the needed type of blood cell Hematopoiesis / cell breakdown continue through life.

Erythrocytes (RBCs)
Most abundant blood cell type Transport gases

Shape is important
Large surface to volume ratio Reversible deformability can change shape

Development is called erythopoiesis

Erythropoietin is a hormone produced by the kidneys in response

to low blood oxygen levels; signals bone marrow to increase RBC production

 Cytoplasm is mostly hemoglobin (lacks organelles) Made up of 4 peptide chains that form the globin

portion and four molecules of the pigment heme which contains an atom of iron Oxygen binds to iron in heme (also CO) 23 % of CO2 is bound to globin portion If there is a problem with any part of the molecule it may not be functional.

RBC breakdown
Healthy RBCs live about 120 days; we break down

about 174 million per minute RBCs are removed from circulation by the liver and spleen Broken down into heme and globin portions Globin is broken down into amino acids Iron is removed from heme and stored or recycled Heme is broken down into biliverdin and then into bilirubin

Usually eliminated in bile. To produce more RBCs, the body needs

sufficient iron and amino acids as well as the vitamins folate (folic acid) and vitamin B12

10

Abnormalities Anemias
Anemia is the inability of the blood to carry

sufficient oxygen to the body. low #s of RBCs lack of hemoglobin

Cinical Manifestations
Pallor Fatigue

Pallor
Weakness; exercise intolerance Dyspnea Syncope (fainting) and dizziness Angina Tachycardia (increased heart rate) Organ dysfunctions

11

Classification of Anemias
Identified by their causes or by the changes that

affect the size, shape or substance of the erythrocyte Terms that end with cytic refer to cell size, and those that end in chromic refer to hemoglobin content. Additional terms: Anisocytosis various sizes Poikilocytosis various shapes

Macrocytic / Megaloblastic Anemia

Characterized by abnormally large stem cells

(megaloblasts) in the marrow that mature into erythrocytes that are unusually large in size, thickness and volume. The hemoglobin content is normal, so these are normochromic anemias.

12

 These anemias are the result of: Ineffective DNA synthesis

Commonly due to folate and B12

(cobalamin) deficiencies malabsorption or malnutrition These cells die prematurely, decreasing the numbers of RBCs in circulation
DNA synthesis is blocked or delayed, but

RNA replication and protein synthesis are normal.

13

Pernicious Anemia
Common megaloblastic anemia Caused by a Vitamin B12 deficiency Pernicious means highly injurious or destructive

this condition was once fatal

Can be congenital baby born with a deficiency in a

protein , intrinsic factor, necessary to absorb B12 from the stomach Adult onset one example is an autoimmune dysfunction - type A chronic atrophic gastritis where there is destruction of the gastric mucosa Most commonly affects people over 30 Females are more prone to PA , and black females have an earlier onset.

14

Pernicious Anemia is also associated with: Heavy alcohol consumption Hot tea Cigarette smoking Other autoimmune conditions Complete or partial removal of the stomach can cause intrinsic factor deficiency

Develops slowly over 20 - 30 years Usually severe by the time individual seeks

treatment Early symptoms ignored because they are nonspecific and vague- infections, mood swings, and gastrointestinal, cardiac or kidney ailments. Usually a degree of neuropathy occurs Untreated, it is fatal, us. due to heart failure

15

Folate deficiency anemias

Folic acid also needed for DNA synthesis
Demands are increased in pregnant and lactating

females Absorbed from small intestine and does not require any other elements for absorption. Folate deficiency is more common than B12 deficiency

16

 Folate deficiency is more common than B12

deficiency , esp. in alcoholics and those who are malnourished because of fad diets or diets low in vegetables. Specific manifestations include cheilosis, (scales and fissures of the mouth), inflammation of the mouth, and ulceration of the buccal mucosa and tongue, magenta tongue.

Atrophy of filliform papillae

Microcytic Hypochromic Anemias

Characterized by abnormally small RBCs that

contain reduced amounts of hemoglobin. Possible causes: Disorders of iron metabolism Disorders of porphyrin and heme synthesis Disorders of globin synthesis

17

Iron Deficiency Anemia

Most common type of anemia throughout the world. High risk: Individuals living in poverty Females of childbearing age Children Common causes Insufficient iron intake

Chronic blood loss even 2- 4 ml/ day

In men gastrointestinal bleeding In women profuse menstruation, pregnancy

Other causes: Use of medications that cause GI bleeding

Surgical procedures that decrease stomach acidity,

intestinal transit time, and absorption Eating disorders such as pica

18

Clinical manifestations:
Early symptoms are nonspecific Later - changes in epithelial tissue: Fingernails become brittle and concave

(koilonychia) Tongue papillae atrophy and cause soreness, redness and burning Corners of mouth become dry and sore Difficulty in swallowing due to web of mucus and inflammatory cells at opening of esophagus

19

Treatment
Stop blood loss
Iron replacement therapy

20

Sideroblastic Anemia
Due to inefficient iron uptake, resulting in abnormal

hemoglobin synthesis Characterized by the presence of ringed sideroblasts in the bone marrow red cells containing iron granules that have not been synthesized into hemoglobin, but instead are arranged in a circle around the nucleus.

http://sickle.bwh.harvard.edu/sideroblast.jpg

21

 Can be acquired or hereditary

Acquired SA is the most common

May be idiopathic or associated with other

disorders Reversible - secondary to alcoholism, drug reactions, copper deficiency and hypothermia Hereditary SA rare, almost always in males probably X-linked recessive gene.

Clinical manifestations
Along with cardiovascular and respiratory

manifestations of anemia, may also show signs of iron overload (hemosiderosis) Enlargement of spleen and liver Bronze tint to skin Heart rhythm disturbances Impaired growth and development in young children

22

Treatment
Drug therapy pyridoxine Iron overload requires repeated blood removal

phlebotomies Iron chelating agents in anemic individuals who require transfusions

Normocytic Normochromic Anemias

RBCs are normal in size and hemoglobin

content, but are too few in number. Less common than the macrocytic and microcytic anemias

23

 Several types that do not have anything else in

common: Aplastic Posthemorrhagic Hemolytic Sickle cell Anemia of chronic inflammation

Aplastic anemia
Fortunately, this condition is rare; it means the RBCs are

not being produced. Bone marrow stem cells are not functioning. Can result from disorders of the bone marrow, such as cancer; autoimmune diseases; renal failure due to lack of erythropoietin; B12 or folate deficiency; congenital problems; or it may be induced by radiation, toxins or the use of some drugs, such as chloramphenicol. Treatment treat the underlying disorder, blood transfusions, and possibly bone marrow transplant

24

Posthemorrhagic
Caused by sudden loss of blood. Can be fatal if loss exceeds 40- 50 % of plasma

volume. Treatment is to restore blood volume by intravenous administration of saline, dextran, albumin, plasma or whole blood.

Hemolytic Anemia
Red blood cells are formed, but are broken down. May be acquired or hereditary. Acquired hemolytic anemia is extrinsic, due to

factors outside the red blood cell, such as an abnormal autoimmune response that targets red cells, or by improper matches during transfusions; or due to infection, systemic diseases, or drugs or toxins.

25

Hereditary or intrinsic hemolytic anemias:

Sickle cell anemia due to a change in one amino

acid in each of the beta-chains in the globin, under conditions of low oxygen the hemoglobin forms insoluble threads that change the shape of the erythrocyte into a crescent. This shape is not as flexible and tend to be trapped in the capillaries, where they obstruct blood flow and cause ischemic injury.

The life span of a sickled cell is only 20 days

rather than 120, and is removed from circulation by the spleen. Either mechanism causes a chronic anemia. Sickle crisis: episodes of acute sickling that block blood flow, posing the threat of widespread and possibly life-threatening ischemic organ damage.

26

http://www.sunyniagara.cc.ny.us/val/sicklecellhigh.html

27

 This is an inheritable condition. If a person has only one defective gene, it is

called sickle cell trait, and the person is essentially normal. This condition tends to persist because it protects against malaria. When a cell becomes infected by the parasite, the cell sickles and is removed from circulation, preventing reproduction of the parasite. Only when a person inherits two defective genes does sickle cell anemia occur.

28

 Thalassemia is another hemolytic disorder where the

alpha or beta chains of the globin are defective, or the beta chain is not produced. When the beta protein is lacking, the alpha protein accumulates and causes destructive membrane effects, causing these cells to be rapidly removed from the circulation. Highest incidence in populations around the Mediterranean and Southeast Asia. Problem occurs when two defective genes are inherited; heterozygotes are essentially normal.

Thalassemia major is an inherited form of hemolytic anemia, characterized by red blood cell (hemoglobin) production abnormalities. This is the most severe form of anemia, and the oxygen depletion in the body becomes apparent within the first 6 months of life. If left untreated, death usually results within a few years. Note the small, pale (hypochromic), abnormally-shaped red blood cells associated with thalassemia major. http://www.nlm.nih.gov/medlineplus/ency/imagepages/1498.htm

29

Myeloproliferative Disorders
The opposite of anemias here we have too many RBCs. Polycythemia excessive production of RBCs

Primary polycythemia cause is unknown, but is in

effect, a benign tumor of the marrow, leading to increased numbers of stem cells and therefore RBCs, and splenomegally. Polycythemia vera rare, mostly Northern European Jewish males between 60 80 yrs.

Secondary Polycythemia
Due to the overproduction of erythropoietin caused

by hypoxia. This is more common. Seen in: Persons living at high altitudes Smokers COPD patients Congestive heart failure patients

30

 Polcythemia leads to : Increased blood volume and viscosity Congestion of liver and spleen Clotting

Thrombus formation
(last two may be due increased numbers of

platelets along with the increase in RBCs due to bone marrow dysfunction.)

Clinical manifestation of Polycythemia

Headache Dizziness Weakness Increased blood pressure

Itching / sweating

31

Treatment of polycythemia
Reduce blood volume by phlebotomy 300-500 ml. Treat underlying condition - Stop smoking Radioactive phosphorus injections Prevent thrombosis

I feel THIRSTY from listening to all of these.

32