Hematology

• Hematology = study of blood (no heart or blood vessels

Fluid and solid matter in the body

• 40% of adult body is solid matter

• 60% is water

• These proportions vary with age (higher % water in babies) and sex (more fat, less water in women)

• Blood accounts for 5% of body fluid = 5-6 liters:

– - about 55% of blood is water

Blood• Total blood volume 5L

– Roughly 8-10% total body weight

– Thicker viscosity than water (obviously…there are cells and proteins in it)

– pH 7.35-7.45 (recall pH homeostasis)

– Normally 38C

• When you donate blood, 1 “unit” = 500 ml (10% total blood volume)

• 2 component groups:– Formed elements (45% total volume)– Blood plasma (fluid portion)

Hematocrit• Proportion of formed

elements (mostly red blood cells) in the blood

• Common medical test

• Plasma: 55%• Formed elements: 45%

• Varies with sex, circumstances

Blood Plasma• Fluid portion of blood (technically the

extracellular matrix of blood…since blood is a form of “connective tissue”)– 90% water

– Straw/yellow tone due to presence

of proteins, various salts (electrolytes),

carbohydrates, lipids, amino acids,

vitamins & hormones

Blood Plasma• Plasma “proteins” ( 7-9% total

plasma ingredients)– Albumins (a family of proteins)

60 % total plasma protein content

• Produced in liver

• Act as carrier/delivery molecules

• Influence blood viscosity– Influence blood pressure through viscosity

– Globulins 35 % total plasma protein • Alpha () & Beta () globulins produced

in liver (fat/lipid transport)

• Gamma () globulins produced by lymphoid cells (“antibodies”)

– Fibrinogen 4 % total plasma protein content

• Produced in liver blood clot (with platelets)

Blood Plasma vs. Serum

• Serum = plasma without fibrinogen• Serum can be harvested by NOT including an anti-

coagulant in a blood draw (allow blood to clot)

With anticoagulant No anticoagulant

Blood Plasma Proteins

• If albumin = 60%, globulin = 35%, fibrinogen = 4%…– 1% of blood protein content = regulatory proteins,

lipoproteins, iron-binding proteins etc.• Recall the ENDOCRINE system

Hematopoiesis• Formed elements are born

in the red bone marrow = Hematopoiesis

• Red blood cell synthesis: erythropoiesis

• White blood cell synthesis: leukopoiesis

• Platelet synthesis: thrombopoiesis

Erythropoiesis: formation of red blood cells

Despite the fact that mature RBC’s have no nuclei, they do “originate” from a cell type that does have a nucleus. During RBC development or “maturation”, the nucleus dissolves.

Red bone marrow produces 2.5 million cells/day

Erythrocytes (red blood cells, RBC’s)• Bi-concave

– Increases surface area for gas exchange (O2 and CO2)

– Permits greater flexibility (allows RBC to flex and squish through tight capillaries)

7.5 m diameter, 2.5 m thick

• No nucleus, no mitochondria– Produce ATP by anaerobic fermentation exclusively

– Without nucleus, there is NO DNA…RBC’s retain mRNA for various protein requirements, but are generally “born” with everything they need to function

Erythrocytes (red blood cells, RBC’s)

120 day lifespan– Lifespan reflects number of “bends & squishes” as well as

hemoglobin function

– Terminated in the spleen & liver

Erythrocytes (red blood cells, RBC’s)• Contain hemoglobin (4 subunit large gas-carrying

protein)– Usually 250-300 billion hemoglobin molecules per RBC– When bound to O2, hemoglobin changes color (diffracts color

light differently)» Oxygenated RBC is bright red - oxyhemoglobin» Deoxygenated RBC is dark purple/red

– NOTE: venous blood still has oxygen…it just doesn’t have as much as arterial blood

– When hemoglobin is carrying CO2: carbhemoglobin

Pathophysiology

• Anemia = low hemoglobin count, or low RBC count– Pernicious anemia = vitamin B12 deficiency = low RBC count

» Autoimmune disease that results in decreased parietal cells in the stomach

» Parietal cells produce intrinsic factor which is required for B12 absorption

– Aplastic anemia = chemical destruction of red bone marrow = low RBC count

– Microcytic anemia = defect in hemoglobin production (usually due to low iron stores)

– Sickle-cell anemia = genetic defect in hemoglobin sequence» Regions of heme molecule cannot hold O2 and

subsequently alter the shape of the RBC

Leukocytes (“white cells”)

• Larger than RBC’s, but fewer in number• Have nuclei, have mitochondria• Motile (can migrate or move by themselves)

– Ameboid motility permits extravasation via “diapedesis”– http://video.google.com/videoplay?docid=-142799799667345

732&q=diapedesis&total=1&start=0&num=10&so=0&type=search&plindex=0

• Characterized by how they “stain”– Cannot really see leukocytes without stains– Eosin & hematoxylin

» Granular leukocytes» Agranular leukocytes

Leukopoiesis

Leukocytes (“white cells”)• Granular leukocytes: Granules = vesicles of digestive enzymes,

reactive oxidants etc.– When attacking an invading pathogen (or autoimmune reaction), will

“degranulate” or exocytose granular contents» Will also phagocytose foreign particles and fuse granules with

them to kill/digest

– Neutrophils: most common granular leukocyte (65% total white cell count) - first line” defenders against bacteria

– Eosinophils: larger than neutrophils (eosinophil = “stained by eosin”)» Phagocytic white cells for parasite and inflammatory and allergic

responses (ex: asthma)

– Basophils: most rare leukocyte» Produce histamine (similar to tissue mast cells)» Involved in allergic responses

Leukocytes (“white cells”)

Agranular leukocytes– No granules…relatively “clear” cytoplasm

– Development takes place in lymphoid tissue

» Lymph nodes, tonsils, spleen & thymus

– Lymphocytes: 30-35% total white cell count

» B-cells differentiate in BONE MARROW (antibody cells)

» T-cells differentiate in THYMUS (“killer”, “helper” etc.)

– Monocytes: largest cells in the blood

» In circulation = monocyte

» When in tissue (after extravasation) = macrophage

» Phagocytic digesters

Platelets - thrombocytes- Originate from megakaryocytes

in red bone marrow that fragment into platelets– No nuclei (no DNA)

– Are capable of extravasation and have ameboid motility

– Very short lifespan (5-7 days)

– Act to form blood clots by altering their plasma membrane

Figure 18.1