Transcript Blood

Introduction to
Hematology
• Hematology is the study of the blood.
• - Blood: is the fluid which cells are free and
suspended.
• It can cross the tissues.
• Has red color.
• Has volume of 5-6 liters, this is 7-8% of the
total body weight.
• Has PH of 7.3-7.4 (alkaline).
• Specific gravity is 1.055-1.056
• It is composed of plasma (~53-58% of the
blood volume), before clotting occurs, and
serum after clotting occurs.
• Plasma consists of 91-92% water, and 8-9% solids.
• Solids are:
Albumin.
Glucose.
Fibrinogen.
Sodium.
Calcium.
Potassium.
Cholesterol.
Magnisium.
Carbon dioxide.
Phosphorus.
Neutral fats.
Glucose.
NPN group.
Oxygen.
• And many other products.
• Also there are such substances, like antibodies,
hormones, complement, and enzymes.
• Cellular parts of the blood (45-47%):
• Consists of:
– The erythrocytes (RBCs) (~45%)
• Contain hemoglobin
• Function in the transport of O2 and
CO2
– The Leukocytes (WBCs) and platelets
(thrombocytes) (~1%)
• Leukocytes are involved in the body’s
defense against the invasion of foreign
antigens.
• Platelets are involved in hemostasis
which forms a barrier to limit blood loss
at an injured site.
• The cells are forming about 45-47% of the
total blood volume in male and 42% in
female. This percentage is determined by
centrifugation and is known as heamatocrit
(PCV), which is the percentage of the packed
red blood cells.
Function of the blood:
• Nutritive: The blood transports nutrients from the
gut to all parts of the body for use or storage.
• Respiratory: the blood carries the oxygen to the
tissue and remove carbon dioxide and other waste
products from the tissues to be excreted by the lung,
kidney, liver, and skin
• The blood regulates the temperature of the body,
because it is constantly in motion.
• Transportive: The blood transports the hormones
from the endocrine glands to the tissues.
• Excretory: To excrete the waste products of
metabolism, for example urea, and uric acid.
Blood Cells
Production
(Hemopoiesis)
Hematopoiesis is a term describing the formation
and development of blood cells.
-- Cells of the blood are constantly being lost or
destroyed. Thus, to maintain homeostasis, the
system must have the capacity for self renewal.
This system involves:
• Proliferation of progeny stem cells
• Differentiation and maturation of the stem cells into the
functional cellular elements.
• In normal adults, the proliferation, differentiation, and
maturation of the hematopoietic cells (RBCs, WBCs, and
platelets) is limited to the bone marrow and the
widespread lymphatic system and only mature cells are
released into the peripheral blood.
Sites of production:
– Fetus: 0-2 months (yolk sac).
2-7 months (liver and spleen).
5-9 months (bone marrow).
– Infants: bone marrow (all bones).
– Adults: vertebrae, ribs, sternum, skull, proximal
ends of the femur, sacrum and pelvis.
• Hematopoiesis in the bone marrow is called
medullary hematopoiesis
• Hematopoiesis in areas other then the bone
marrow is called extramedullary hematopoiesis
• Extramedullary hematopoiesis may occur in fetal
hematopoietic tissues (liver and spleen) of an adult when
the bone marrow cannot meet the physiologic needs of
the tissues. This can lead to hepatomegaly and/or
splenomegaly (increase in size of the liver or spleen
because of increased functions in the organs).
• Hematopoietic tissue includes tissues involved
in the proliferation, maturation, and
destruction of blood cells.
Definitions:
• Thrombocytopenia: decrease in platelets in the
blood.
• Splenectomy: removal of the spleen.
• Hypersplenism (splenomegaly) – in a number of
conditions the spleen may become enlarged.
• Leukopenia: decreased in WBCs.
• Thrombocytopenia: decreased in platelets.
• Pancytopenia: when all three cells types are
decreased.
Derivation of blood cells
• The committed lymphoid stem cells will be
involved in lymphopoiesis to produce
lymphocytes
• The committed myeloid stem cell can
differentiate into any of the other
hematopoietic cells including erythrocytes,
neutrophils, eosinophils, basophils,
monocytes, macrophages, and platelets.
Erythrocyte:
• Normal erythrocyte is a round biconcave disk like cell; it is
non-nucleated, containing haemoglobin. It measures about
7.2-7.8 microns.
• Life span: the average is 80-120 days.
• Function: RBC carry oxygen from the lung to the body cells
and carry carbon dioxide from the body cells to the lung.
• Erythrocytosis: increased in the blood cells
count, which may lead to polycythemia:
increasing in the Hemoglobin concentration
above 18.5 g/dl in adult males and 15.5 g/dl in
adult females, with elevated haematocrit and
RBCs count.
• Reticulocyte: is a very young erythrocyte which
contains remainant of RNA. The precipitated
RNA is seen when stained with a supravital
stain such as new methylene blue or brilliant
crystal blue dyes.
• Reticulocytosis: increased blood reticulocyte
count.
Hemopoietic tissues produce blood cells:
• Red bone marrow produces RBCs, WBCs
and platelets
• Stem cells called hemocytoblasts multiply
continually and are pluripotent (capable
of differentiating into multiple cell lines)
committed cells are destined to continue
down one specific cell line
• Stimulated by erythropoietin,
thrombopoietin and colony stimulating
factors (CSFs).
Erythropoietin and Its Receptor
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About 90% is produced in the kidney, and the rest is
produced in a variety of extrarenal sites.
The signal that causes erythropoietin-secreting cells to
synthesize and release the cytokine is hypoxia.
Whenever the oxygen level within the cytoplasm of
erythropoietin-producing cells falls below a critical
level, erythropoietin is synthesized and secreted into the
bloodstream.
Once synthesized and released from the cell,
erythropoietin travels in the bloodstream to the bone
marrow, where it binds to receptors on erythroid cells,
thereby initiating their proliferation and differentiation.
Erythrocyte Homeostasis:
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Classic negative feedback control
Hypoxemia in kidneys
EPO production ↑
Stimulation of bone marrow
RBC count ↑ in 3-4 days
Stimuli for erythropoiesis
• Low levels of O2
• Increase in exercise
• Hemorrhaging
Erythrocyte Production
• Erythropoiesis produces 2.5 million
RBCs/second from stem cells
(hemocytoblasts) in bone marrow
• First committed cell is proerythroblast
• Has receptors for erythropoietin (EPO)
from kidneys; EPO stimulates
development of erythroblast
• Erythroblasts multiply & synthesize
hemoglobin
• Normoblasts discard their nucleus to form a
reticulocyte named for fine network of
endoplasmic reticulum
• Enters bloodstream as 0.5 to 1.5% of circulating
RBCs
• Development takes 3-5 days & involves
• Reduction in cell size, increase in cell number,
synthesis of hemoglobin & loss of nucleus
• Blood loss speeds up the process increasing
reticulocyte count
Nutritional Needs for Erythropoiesis
• Iron :
• is key nutritional requirement for erythropoiesis
• Lost daily through urine, feces, and bleeding
• Low absorption rate requires consumption of 0.5-2
mg/day
• Dietary iron in 2 forms: ferric (Fe+3) & ferrous
(Fe+2)
• Stomach acid converts Fe+3 to absorbable Fe+2
• Gastroferritin from stomach binds Fe+2 &
transports it to intestine
• Absorbed into blood & binds to transferrin to
travel bone marrow uses to make hemoglobin,
muscle used to make myoglobin and all cells
use to make cytochromes in mitochondria
• Liver binds surplus to apoferritin to create
ferritin for storage
• B12 & folic acid (for rapid cell division)
• vitamin C & copper (for cofactors for enzymes
synthesizing RBCs)
Leukocyte Production
(Leukopoiesis)
• Committed cell types -- B and T progenitor
lymphocytes and granulocyte-macrophage colonyforming units
• Possess receptors for colony-stimulating factors
released by mature WBCs in response to infections
• Red bone marrow stores and releases granulocytes
and monocytes
• Some lymphocytes leave bone marrow unfinished
go to thymus to complete their development (T
cells)
• Circulating WBCs do not stay in bloodstream
• Granulocytes leave in 8 hours & live 5 days longer
• Monocytes leave in 20 hours, transform into
macrophages and live for several years
• WBCs providing long-term immunity
• (lymphocytes) last decades
Leukocyte Descriptions (WBCs)
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Granulocytes
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eosinophils - 2-4%
basophils - <1%
neutrophils - 45-70%
Agranulocytes
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Lymphocytes (B and T cells) - 25-33%
Monocytes - 3-8%
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Granulocyte Functions
Neutrophils ( in bacterial infections)
Phagocytosis of bacteria.
Releases antimicrobial chemicals.
Eosinophils ( in parasitic infections or allergies)
Phagocytosis of antigen-antibody complexes,
allergens & inflammatory chemicals.
• Release enzymes destroy parasites such as worms.
• Basophils ( in chicken pox, sinusitis,
diabetes)
• Secrete histamine (vasodilator).
• Secrete heparin (anticoagulant).
Agranulocyte Functions
• Lymphocytes ( in diverse infections & immune
responses)
• Destroy cancer & foreign cells & virally infected cells
• “Present” antigens to activate other immune cells
• Coordinate actions of other immune cells
• Secrete antibodies & provide immune memory
• Monocytes ( in viral infections & inflammation)
• Differentiate into macrophages
• Phagocytize pathogens and debris
• “Present” antigens to activate other immune cells (APC)
Platelet Production
(Thrombopoiesis)
• Hemocytoblasts that develop receptors for
thrombopoietin from liver or kidney become
megakaryoblasts
• Megakaryoblasts repeatedly replicates its DNA without
dividing forms gigantic cell that remains in bone marrow
called megakaryocyte (100 μm in diameter)
• Infoldings of megakaryocyte cytoplasm splits off cell
fragments that enter the bloodstream as platelets (live for
10 days)
• Some stored in spleen and released as needed
• Platelets
• Small fragments of megakaryocyte cytoplasm, 2-4 μm
diameter & containing “granules”
• Pseudopods provide amoeboid movement & phagocytosis.
Functions:
• Secrete clotting factors, growth factors for endothelial
repair, and vasoconstrictors in broken vessels.
• Form temporary platelet plugs.
• Dissolve old blood clots.
• Phagocytize bacteria.
• Attract WBCs to sites of inflammation.