Blood Flashcards
Properties of Blood
- bright to dark red color
- viscous
- slightly alkaine (pH - 7.4)
- average total blood volume is 5 L/ 5.5kg
Content of Blood
Blood is a specialized type of connective tissue composed of
- formed elements, or blood cells
- plasma
Blood cells:
1) erythrocytes (red blood cells’ RBCs)
2) leukocytes (white blood cells; WBCs)
3) platelets
Plasma
Fluid component of blood comprising of about 55% of total blood volume
Pale yellow aqueous (90%) solution
- proteins (7-8%) - electrolytes and ions (0.9- 1%) - organic molecules
Plasma Proteins
Albumin - most abundant (>50% of total plasma protein coming from the liver
- maintains colloid osmotic pressure of plasma
- carrier protein of insoluble metabolites, hormones, etc.
Globulins ( alpha, beta, and gamma)
- gamma immunoglobulins
> antibodies secreted by plasma cells (B cells) and lymphocytes)
> function in Immunity
Alpha and Beta non-immune globulins:
Source: liver
Transport substances in the body and maintain osmotic pressure
Fibrinogen
Source: liver
Function: formation of blood clots
Other Plasma Components
Electrolytes (Ca2+, Fe2+ Na+ K+ Cl- Mg2+ HCO3- PO43- SO42-)
- Regulate osmotic balance and maintain pH - imbalance of electrolytes - serious medical condition
Nutrients: Amino Acids, glucose, lipids,
- building blocks of macromolecules and production of energy
Enzyme: alkaline phosphatase (ALP), creatinine kinase (CK) < asparatate transmaminase (AST) lactate dehydrogenase (LDH)
Hormones
Blood gases: (O2 diffuses OUT and Co2 diffuses IN)
Waste products: urea, uric acid, creatinine, ammonium salts
> transported to kidneys for removal from the body
Serum
clear yellow liquid that separates from the coagulum (clot) when centrifuged
Basically, serum is plasma without clotting factors in it because all of the clotting factors went to forming a CLOT (blood cells)
Layers of a centrifuge tube
3 layers:
Bottom - red blood cells
Upper - plasma
Middle - “buffy coat” white blood cells and platelets
**when the tube is coated with anti-coagulant, there is no no clotting; Anti-coagulants include heparin, EDTA, and citrate
Blood Cell Types
Erythrocytes or mature red blood cells (RBCs)
Platelets (thrombocytes)
Leukocytes or white blood cells (WBCs) Neutrophils Eosinophils Basophils Monocytes Lymphocytes
Erythrocytes or mature red blood cells (RBCs)
- Most numerous
- red color because of hemoglobin
- survival in circulation = 120 days
- transport Oxygen from lungs to tissues and Carbon Dioxide away from tissues
Leukocytes or white blood cells (WBCs)
- Least numerous
- Neutrophils: most numerous in 8-10 hrs of circulation
> defense against bacterial and fungal infection
-Eosinophils: 4-5hrs in circulation
> defense against parasitic infestation and dampen allergic response
Basophils (<1% of WBCs)
> mediate anaphylactic and inflammatory rxns
- Neutrophils: most numerous in 8-10 hrs of circulation
Leukocytes or white blood cells (WBCs)
- Least numerous
Neutrophils: most numerous in 8-10 hrs of circulation
> defense against bacterial and fungal infection
Eosinophils: 4-5hrs in circulation
> defense against parasitic infestation and dampen allergic response
Basophils (<1% of WBCs)
> mediate anaphylactic and inflammatory rxns
Monocytes (5% of WBCs)
- 10hrs in circulation - mature into macrophages - responsible for removal of unwanted aged cells and other debris - produce cytokines required for inflammatory and immune response
Lymphocytes (33% of WBCs)
- variable lifespan
- T-lymphocytes: 40-80% of lymphocytes; CELL MEDIATED IMMUNITY
- B-lymphocytes: 10-30% lymphocytes; HUMORAL IMMUNITY
Function of Blood
1) Transport of Nutrients and Waste Products
- nutrients from gut to cells
- waste products of metabolism away from cells for excretion
2) Respiratory gas transport
- Oxygen to cells and Carbon dioxide away from cells through hemoglobin
3) Thermoregulation
- absorbing large amounts of heat energy for a small temperature rise
- control of blood flow via vasoconstriction - vasodialation
4) Maintenance of homeostatsis
- maintenance of acid-base balance and osmotic pressure of body fluids
5) Hemostasis
- clot formation after injury to prevent blood loss
6) Immunity
- contains and transports cells of the immune system to protect the body
Standard Blood Test (Hematology)
CBC = Complete Blood Count
• RBC count: x 1012 / L (millions / mL)
• Hematocrit (Hct) or packed cell volume (PCV) - %
o Amount of space (volume) RBCs take up in blood
• Hemoglobin (Hb) – g / dL or g / L
o Amount of Hb in blood
• RBC Indices: based on other meas. in a CBC
o Mean corpuscular (cell) volume (MCV)
o Mean corpuscular (cell) hemoglobin (MCH)
o Mean corpuscular (cell) hemoglobin concentration (MCHC)
o Red cell distribution width (RDW)
• Mean corpuscular (cell) volume (MCV) – fL (10-15)
o Average volume of RBCs
o Measure of RBC size
o (Hct / RBC #) x 10
• Mean corpuscular (cell) hemoglobin (MCH) – pg
o Average weight of Hb in an RBC
o Measure of RBC weight
o (Hb / RBC #) x 10
• Mean corpuscular (cell) hemoglobin concentration (MCHC) – g / dL
o Average concentration (relative to cell size) of Hb in an RBC
o Measure of how many RBCs in a certain amount of fluid
o (Hb / Hct) x 10
• Red cell distribution width (RDW) - %
o Measure of size variation of RBCs
• WBC count - x 109 / L (thousands / mL)
• WBC Differential count: o Neutrophils o Lymphocytes o Monocytes o Eosinophils o Basophils
• Platelet count - x 109 / L (thousands / mL)
• Mean Platelet Volume (MPV) – fL
o Measure of the average amount (volume) of platelets
Blood Smears
Thin layer of blood spread on a glass slide to form a blood film
Blood cells are preserved by fixation (methanol fixation usually)
Fixed film is stained so that individual cells can be recognized under the microscope
Criteria for Leukocyte Identification
Cell size/shape
Nuclear size (nucleus to cytoplasm ratio)
Nuclear shape
Cytoplasmic staining
Cell inclusions (granules)
Blood Stains
Romanowsky stains (all of which contain two dyes of Tolene blue and Eosin)
- Wright's stain - simpler method - Giemsa stain - more complex stain; for delicate staining characteristics and detection of blood parasites - May- Grunwald stain - good for routine work
Appearance of Blood Cells on Blood Films
- RBCs: reddish-pink
- Platelets: purple
• Neutrophils: dark purple nuclei, reddish
granular cytoplasm
• Lymphocytes: dark purple nuclei, varying
shades of blue cytoplasm
• Monocytes: lighter purple nucleus, gray-
blue cytoplasm
- Eosinophils: bright red/orange granules
- Basophils: dark purple nuclei and granules
Red Blood Cells (RBCs) - Erythrocytes
• Erythropoiesis: the process of RBC formation
• RBCs: made in bone marrow under the influence of erythropoietin (Epo)
produced by the kidneys
• Characteristics:
o Smallest and most numerous (5 x 1012 / L)
o Plasma membrane but no nucleus (anucleate) or organelles
o Immature RBCs have nucleus but lose it as they mature
o No DNA/RNA, thus no cell division
o Packed with Hb – gives them red color
o Major role – carry O2 to & CO2 away from tissues
Immature RBCs –
Reticulocytes
- Still have small amounts of ribosomal RNA
- Slightly larger than mature RBCs, no nucleus
- Tend to stain slightly bluer than mature RBC’s on Wright’s stain
- Circulate for 1 day and undergo removal of RNA
• Can be detected using supravital staining – identifies RNA filaments
NOTE Supravital staining can stain living cells!!
• The reticulocyte count is an important marker of RBC production – BM activity
Characteristics of Red Blood Cells (Erythrocytes)
o Shape: highly flexible biconcave discs
o 80-100 femtoliters in volume, 140mm2 area
o Flexibility essential for:
§ Maximizing surface area:volume ratio for gas exchange
§ Passage through smallest capillaries
o Produced in BM, approx. 7 days for maturation
o Lifespan: 120 days – 300 miles around the body
o 1 circulation cycle: 20 secs
o Spleen: RBCs graveyard
High reticulocyte count (Reticulocytosis): more made in Bone Marrow
o Premature destruction of RBCs (i.e. hemolysis)
o Anemia due to premature destruction of RBCs
o Bleeding
o High altitude
Low reticulocyte count: poor production in Bone Marrow
o Anemia due to decreased production of RBCs
o Vitamin / mineral deficiency
o BM malignancy
o Radiation (chemotherapy)
o Chronic infection
o Drugs
Hemoglobin (Hb)
large protein composed of 4 amino acid chains, globin chains, each bound to an iron containing heme group
- The heme group consists of an iron (Fe) ion, which is the site of O2 binding
- Hb also carries CO2 that binds to N-terminal groups of the globin chains
• Synthesis:
o Heme in mitochondria and cytoplasm of immature RBCs
o Globin protein in cytoplasm by ribosomes
• Normal Hb: 6 globin chains; a-cluster: a, and z; b-cluster: b, g, d, and e
o 3 -10 wks gestation: z and e
o Fetus: Hb F - a2g2
o Adult : Hb A - HbA1: a2b2 (97%); HbA2: a2d2 (2-3%); HbF (1%)
o Oxyhemoglobin: Hb carrying O2
oCarbaminohemoglobin: Hb carrying CO2
• Abnormal Hb:
o Carboxyhemoglobin: binds to CO instead of O2
o Methemoglobin: Fe2+ to Fe3+; cannot bind O2
RBC Assessment
Number
Size
Color
Shape
Distribution in blood smear
Red cell inclusions
RBC Assessment with Numbers
measured by automated counters; also in blood smear
o Increased number: erythrocytosis (POLYCYTHEMIA)
o Decreased number: anemia, erythropenia (ERYTHROCYTOPENIA)
RBC Assessment with Size
MCV by automated counters; also in blood smears
o Same or variable size:
ANISOCYTOSIS
o Normal: NORMOCYTIC
o Small: MICROCYTIC
o Large: MACROCYTIC/ MEGALOCYTIC
RBC Assessment with Color
blood smear; [Hb]
o Normal: NORMOCHROMIC
o Pale: HYPOCHROMIC
o Darker: HYPERCHROMIC
RBC Assessment with Shape
POIKILOCYTOSIS
o Normal biconcave vs. different and oddly shaped cells
RBC Assessment by Distribution in Blood Smear
o Rouleaux: like stacks of coins; due to increase in high MW plasma proteins
o Red Cell Agglutination: due to antibody on surface of RBCs
RBC Assessment by Red Cell Inclusions
o Pappenheimer Bodies: small basophilic inclusions in cell periphery
o Basophilic Stippling: small basophilic inclusions throughout cell
o Howell-Jolly Bodies: large round densely stained inclusions on
edge of cell; nuclear remnant
Polycythemia (erythrocytosis)
increased # of RBCs, Hb, Hct and can be absolute or relative
o ABSOLUTE: Primary or Secondary
> Primary: overproduction of RBCs (Polycythemia (rubra) Vera (PV)
>Secondary: caused by increased erythropoietin (Epo)
secretion due to hypoxia
• High altitude
• Cigarette smoking
• COPD
• Renal and heart
disease
o RELATIVE: due to dehydration and fluid loss
> Diuretics, diarrhea, vomiting, burns
Polycythemia (Rubra) Vera (PV)
o PRIMARY POLYCYTHEMIA
o Myeloproliferative disease; rare
o Due to increased RBC proliferation in bone
marrow (BM)
o Cause not known; mutation in JAK-2 gene (diagnostic test?)
o Clinical features:
Red complexion
Viscous blood
Splenomegaly
Gums bleeding
o Treatment
Therapeutic phlebotomy
Blood thinners (e.g. aspirin)
Anemia
decreased # of RBCs in blood due to
1. Blood loss – acute or chronic 2. Decreased production of RBCs - Iron deficiency anemia - Megaloblastic/macrocytic anemia – B12/Folic acid - Sideroblastic anemia - Anemia of chronic disease - Thalassemia (a, b)
o Increased destruction of RBCs
- Hemolytic anemia
- Hereditary spherocytosis
- G6PD deficiency
- Sickle cell disease
o Almost 1/3 of the world’s population is anemic!
Causes of Anemia
Rate of RBC production ≠ rate of RBC destruction > CAUSES:
o Blood loss (bleeding): acute (trauma) or chronic (ulcers,
menstruation)
o Insufficient RBC production by BM: microcytic (low MCV) or macrocytic (high MCV)
o Insufficient HB concentration in RBCs
o Accelerated RBC destruction: hemolysis (hemolytic)
o Cause is distinguished by reticulocyte count
> Decreased in state of decreased production
> Increased in RBC destruction
IRON DEFICIENCY ANEMIA
o Decreased RBC Production: Microcytic Anemia (most common)
o Insufficient iron stores due to
• Poor diet
• Poor iron absorption / utilization
o Body iron stores are depleted by prolonged bleeding
o Common in menstruating and pregnant women
o CBC: low reticulocytes, MCV, MCH, iron, ferritin (iron-storing
protein)
o Blood smear: hypochromic microcytes
SIDEROBLASTIC ANEMIA
o Decreased RBC Production: Microcytic Anemia
o Abnormal incorporation of iron into the heme group of Hb
o Toxic accumulation of iron in mitochondria = ringed sideroblasts
o Classified as:
§ Hereditary – deficiency of enzyme involved in heme
synthesis
§ Secondary - drug-induced or alcohol-induced, lead poisoning
§ Idiopathic – cause not known; primarily in elderly
o Blood smear: sideroblasts, basophilic stippling
ANEMIA OF CHRONIC DISEASE
o Decreased RBC Production: Microcytic Anemia (second most common)
o Cause:
§ Chronic infection
§ Chronic inflammatory diseases (rheumatoid arthritis)
o Mechanism: blocked iron transport from storage sites to
developing RBC in BM
o Associated with renal failure and decreased erythropoietin production
o Blood smear: marked rouleaux formation due to increased plasma
protein concentration
THALASSEMIAS
o Decreased RBC Production: Microcytic Anemia
o Inherited genetic disorders
o Reduced or absent production of normal Hb A
o Thalassa - sea, haima - blood; most common in Mediterranean Sea
area
o 2 types:
1. a thalassemia – caused by deletion of 1, 2, 3, or 4 alpha
globin genes
- b thalassemia – caused by mutations in the beta globin
gene cluster
Alpha Thalassemia
• Deficiency or no synthesis of a-globin chains
• Severity of disease depends on number of a-globin chains deleted
o 1 a-globin gene: “silent” carriers who are asymptomatic; only identified by pedigree and DNA
analyses
o 2 a-globin genes: a-thalassemia trait:mild hypochromic microcytosis o Identified by pedigree and DNA analyses
o 3 a-globin genes: hemoglobin H disease
o 4 a-globin genes: hemoglobin Barts hydrops fetalis
a Thalassemia – Hemoglobin H disease
o Hemoglobin H disease: production of Hb H (b4)
o moderately severe hypochromic microcytic anemia (due to
reduced Hb synthesis and hemolysis)
o Blood smear: hypochromic microcytosis, target cells, tear-drop
cells, inclusions (precipitated Hb H; cause of hemolysis)
a Thalassemia Major – Hemoglobin Barts Hydrops Fetalis
o Most severe form of a-thalassemia
o Complete absence of a-globin chains; hemoglobin Barts (g4)
o Incompatible with life: stillbirth by 3rd trimester or shortly after delivery
- Hydrops fetalis: fluid buildup in multiple organs, cardiac failure
- Toxemia in mother carrying fetus with Barts hydrops fetalis
b Thalassemia minor (trait)
o Mildest form; one b-globin gene is defective
o Moderately reduced Hb A1; increased Hb A2 (4-8%) and Hb F (2-
5%)
o Asymptomatic
o High RBCs (distinct from iron iron deficiency)
o Blood smear: hypochromic microcytic, target cells, basophilic
stippling
o Genetic counseling; 2 parents with b-thalassemia trait
= 1 in 4 chances to have a child with b-thalassemia major
= 1 in 2 with b-thalassemia trait
= 1 in 4 healthy
b Thalassemia major (Cooley’s anemia)
o Most severe form; both b-globin genes are defective
o Reduced or absent Hb A1; increased Hb A2 and Hb F (up to 98%)
o Blood smear: hypochromic microcytosis, target cells, nucleated
red cells, tear drop cells, fragmented cells
o Signs and Symptoms: after 6 months of age
o Prognosis: average life 17 years, die by 30 years due to
cardiotoxicity
Macrocytic Anemias
- Elevated MCV
- Impaired DNA synthesis but normal RNA synthesis
• Usually due to B12 and folic acid deficiency due to
o Inadequate dietary intake (in vegans), poor diet (no fresh fruits/vegetables) or overcooked food
o Intestinal malabsorption due to lack of intrinsic factor
(gastrectomy, pernicious anemia), alcoholism, drugs
(anticonvulsive)
o Increased requirements during pregnancy
- B12: years to develop deficiency because of sufficient body stores
- Folic acid deficiency develops fast; body stores only for 3 months
• B12 and folic acid deficiency
o Folic acid deficiency: neural tube defects (e.g. spina bifida)
• Blood smear: macrocytosis, oval cells, tear-drop cells, red cell
fragments; hypersegmented neutrophils, circulating nucleated red
cells (severe cases)
