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8/4/2019 Blood Histology
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BLOOD
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BLOOD...
y TISSUE
y Composed of: ERYTHROCYTES, LEUKOCYTES andTHROMBOCYTES
y Suspended in fluid : PLASMA (transparent yellow fluidthat constitute the extracellular matrix of the bloodtissue)
y Normal vol of blood in the body: 5-6 Liters (7% 0f thebody weight)
yErythrocytes = 45%
y Leukocytes and platelets = 1%
y Plasma = 54%
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Study of blood...
y Microscopic study of blood cells (PERIPHERAL
BLOOD STUDY) = uses stained blood smears
y Yields the following information: diseases that
primarily affect the blood; indirect evidences of
viral, bacterial, and parasitic infections
y This study will enable clinicians to identify the
disease, follow its course, and evaluate theeffectiveness of treatment
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PERIPHERAL BLOOD FILM ((Wrights
stained)
Elements of BLOOD:
Erythrocytes
Leukocytes
Thrombocytes
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RED BLOOD CELLS:Shape andSize
y Biconcave discs in shape;
y bag that can be deformed into almost any shape
y Normally, the RBCs have a great excess of cell membrane
relatively compared to the quantity of the material insidey With this, deformation does not stretch the membrane great
greatly and does cause rupture
y This shape can change remarkably as the RBCs pass thru the
capillaries
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Three Dimensional RBC
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The biconcave shape..
y This shape presents a surface area 20-30% greater in relation
to its volume than it would have if it were spherical
y This increased surface area favors the immediate saturation of
its hemoglobin with OXYGEN as the erythrocytes pass thruthe pulmonary capillaries
y Total surface AREA of the RBC in an average human:
3,800sqm3,800sqm (this is 2000X the surface area of the body)
y
This leads to great efficiency in oxygen and carbon dioxidetransport
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Areas ofthe bodythatproduce the
RBCs.
y Early embryonic life: in the YOLK SAC (primitive nucleated
RBCs)
y Middle trimester of gestation: in the LIVER,
majoritySPLEEN & LYMPH NODES, minorityy Last month of gestation and after birth: exclusively in the
BONE MARROW
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Amongthe bones.
y The marrow of essentially ALL BONES produces red bloodcells until the person is 5 years old5 years old
y The marrow of the long bones (except the proximal
portions of the humeri and tibiae) until20
years old20
years old
they become quite fatty
y After 20years of age, red blood cell production occur
only in the marrow of MEMBRANOUS BONES
(vertebrae, sternum, ribs, and ilia)y ***the marrow becomes less productive as age increases
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GENESIS OF RBCS
y Proerythroblast
y Basophil erythroblast (stain with basic dyes)
y Polychromatophil erythroblast
y Orthochromatic erythroblast y Reticulocyte
y Erythrocyte
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RETICULOCYTEy The RBC is already filled with hemoglobin to a concentration
of 34% in this stage
y The form of RBC wherein the nucleus is condensed to asmall size, with its remnant being extruded, while the ER is
reabsorbedy It still contains a small amount of basophilic material,
consisting of remnants of Golgi apparatus, mitochondria, andorganelles
yIts movement from the bone marrow to the capillaries:DIAPEDESISDIAPEDESIS (squeezing thru the pores of thecapillary membranes)
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Genesis ofRBC
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Before enteringthe circulation..
y Immature red blood cells extrude their nucleus =>
y Losing their capacity for DNA-directed protein synthesis =>
y Mitochondria and other organelles are also lost =>
y Reduced to a membrane-bound corpuscle cytoplasm thatconsists predominantly HEMOGLOBIN=>
y Perform their primary function
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RED BLOOD CELLS
y FUNCTIONS:
Transport ofHemoglobin => main or major function
Transport ofCarbonic anhydrase = this enzyme catalyzes,
hastens, and fastens the reaction between CO2 & H2O=>CO2 becomes transported from the tissues to the lungs
in the form of bicarbonate ion (HCO3-)
Hemoglobin is an excellent ACID BASE BUFFER (as most
protein is) => RBCs are responsible for most of thebuffering power of the whole blood
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Normal count ofRBC
y 5.4 M/mm in men
y 4.8M/mm in women
yy These values become slightly increased by residence in high altitudeThese values become slightly increased by residence in high altitude
placesplaces
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VARIETIESINSHAPEAND
MORPHOLOGY ofERYTHROCYTES
y Hypotonic solution can make the RBC swell => stretches
the membrane => leaky, permitting hemoglobin to escape
=> leaving behind an empty membrane =>
ERYTHROCYTE GHOSTERYTHROCYTE GHOST
y Conditions of low ATP => RBCs are transformed =>
become round up with 10-30 short conical projections
radiating from the surface => ECHINOCYTES,ECHINOCYTES, and theand the
adoption process is called CRENATIONadoption process is called CRENATION
yy CrenationCrenation: can be also induced during exposure to: can be also induced during exposure to
anionic compounds, fatty acids, oranionic compounds, fatty acids, or lysolecithinlysolecithin
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REGULATION OF RBC PRODUCTION
yy WHY IS THERE A NEED TO REGULATE RBCWHY IS THERE A NEED TO REGULATE RBC
PRODUCTION?????PRODUCTION?????
Regulation is within narrow limits so that an adequate
number of red cells is always available to provide sufficienttissue oxygenation
Regulation is also not above the narrow limits so that the
cells do not become so concentrated that they impede blood
flow
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REGULATORS..y 1.Tissue Oxygenation basic regulator of RBC production
Any condition that causes the quantity of oxygentransported to the tissues to decrease increases therate of RBC production
Severe hemorrhage severe anemia BM begins toproduce large quantities of RBCs
Destruction of major portions of the bones ( byradiation) => BM works hard to produce RBCs =>hyperplasia of remaining BM tissue
Very high altitudes =>quantity of oxygen in the air isdecreased => insufficient O2 is transported to thetissues => RBC production becomes increased
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Remember.
yy Itis notthe concentration of RBCs inthe bloodthatItis notthe concentration of RBCs inthe bloodthat
controls the rate of RBCproduction,BUTthe functionalcontrols the rate of RBCproduction,BUTthe functional
ability ofthe RBCs to transport oxygento the tissues inability ofthe RBCs to transport oxygento the tissues in
relationto the tissue demand for oxygen.relationto the tissue demand for oxygen.
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Diseasedstates can also regulate
yy Some diseases ofthe circulationthat cause decreased bloodSome diseases ofthe circulationthat cause decreased blood
flowthru the peripheralvessels andthose that cause failureflowthru the peripheralvessels andthose that cause failure
of oxygen absorption bythe blood as it passes thru the lungsof oxygen absorption bythe blood as it passes thru the lungs
can also increase the rate of RBCproductioncan also increase the rate of RBCproduction.
y Examples: prolonged cardiac failure; lung diseases tissue hypoxia resulting from these diseased state
increases the rate of RBC production => increase in
hematocrit => increase in total blood volume
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REGULATORS. .
y 2. ERYTHROPOIETIN.This circulating hormone
(glycoprotein) is the principal factor that stimulates RBC
production
Hypoxia has little effect or no effect in stimulating RBCproduction in the ABSENCE of ERYTHROPOIETIN
If the erythropoietin system is FUNCTIONAL, hypoxia
can cause the marked increase in erythropoietin
production which in return enhances RBC productionuntil hypoxia is relieved
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ERYTHROPOIETIN
y 90% is formed in the KIDNEYSKIDNEYS (in the juxtaglomerular
portion or by the renal tubular epithelial cells)
y 10% is secreted or formed by the LIVERLIVER
yy When both kidneys are removed or destroyed by
When both kidneys are removed or destroyed by
disease, the person becomes invariably anemicdisease, the person becomes invariably anemic thethe
remaining 10% produced by the liver can cause orremaining 10% produced by the liver can cause or
effect only 1/3 to RBC formation as needed byeffect only 1/3 to RBC formation as needed by
the bodythe body
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ERYTHROPOIETIN
y It begins to be formed within minutes to hours and reaches a
maximum production at 24HRS when a person is placed in a
low oxygen condition
y
Yet no new RBCs appear circulating in the blood until about5days later
y Reason: erythropoietins important effect is to stimulate the
production of PROERYTHROBLASTS from the
hematopoietic stem cells in the BM
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ERYTHROPOIETIN
y This hormone also hastens the genesis of RBC
y Causes the proerythroblasts to pass more rapidly thru the
different erythroblastic stages than normally => speeding up
production of new cellsy This rapid production continues as long as the person
remains in a low oxygen state or until enough red cells are
produced to carry adequate amount of O2 to the tissues
despite the low oxygen
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ERYTHROPOIETIN
y In the absence of erythropoietin, few RBCs are produced by
the BM
y In the presence large quantities of erythropoietin and in the
presence of plenty of iron and other other nutrients => rateof RBC production can rise to 10X or more the normal
the ERYTHROPOIETIN CONTROL MECHANISM forRBC production is a powerful one
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MATURATION OF RED BLOOD CELLS
y NUTRITION plays and great affects the maturation and
rate of RBC production
y Two important VITAMINS: VITAMIN B12 and FOLIC
ACIDy Both are essential for the synthesis of DNA; both are
required for the formation of thymidine triphosphate, an
essential building blocks of DNA
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Lack ofVit B12/Folic Acid
Failure of nuclear maturation and division
Diminished DNA
Lack of Vit B12 and Folic Acid
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Consequence
y Failure to proliferate rapidly
y Type of cells produced: MACROCYTES
y Larger than normal, with flimsy membrane
y Irregular, large and oval, instead of the usual biconcave discy MACROCYTES are capable of carrying oxygen normally, but
are considered fragile
y Fragility causes them to have short life, one-half to one-third
normaly Vit B12 and Folic Acid Deficiency: causes MATURATION
FAILURE in the process of eryhtropoiesis
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What causesthe abnormality in the
function and morphology?
abnormality
Inability of the cells to synthesize adequate quantities of DNA
Slow production of the cells, but does not prevent excess formation ofRNA by the DNA in those cells that do not succeed in being produced
Cellenlargement
Quantity of RNA in each cell becomes greater than normal
Excess production of cytoplasmic Hgb and other constituents
Abnormalshape
Abnormalities of all the cells DNA
Structural components of the cell membrane andcytoskeleton are also malformed=> abnormal cell shapes andincreased cell membrane fragility
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MATURATION FAILURES (Diseases)
y PERNICIOUS ANEMIA
Causes maturation failure due to failure to absorb Vit
B12 from the GIT
Basic abnormality is an atrophic gastric mucosa => fails
to secrete normal gastric secretions
One of the important secretions of the parietal cells of
the gastric glands: INTRINSIC FACTOR
Intrinsic Factor: combines with Vit B12 from the food,
and makes the B12 available for absorption by the GIT
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Upon absorption ofVit B12
y Once Vit B12 has been absorbed from the GIT, it is stored in
large quantities in the liver (stores up to 1000x the normal
level)
y It is released slowly as needed to the bone marrow and other
tissues of the body
y RDR to maintain normal RBC maturation:1-3microgram
y 3-4years of defective B12 absorption are requiredto
cause maturation failure anemia
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MATURATION FAILURES (Diseases)
y FOLIC ACID DEFICIENCY
(PTEROYLGLUTAMIC ACID) CAUSED BY GIT absorption abnormalities, like sprue
(small intestinal disease) Difficulty in absorbing both the Vit B12 and Folic Acid
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SYNTHESIS/FORMATION OF
Hemoglobin
y Begins in the proerythroblasts
y Continues slightly even into the reticulocyte stage
y When the retic leaves the BM and passes into the blood
stream => continue to form minute quantities of HgB foranother day or so
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SYNTHESIS OF HgB
Protoporphyrin IX
Combines with IRON
Formation of Pyrrole molecule
Four Pyrrole molecules combine
Succinyl-CoA (formed in the Krebs Cycle
Binds with glycine
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SYNTHESIS ofHgB
Four Hemoglobin chain bind together loosely toform
WHOLE HEMOGLOBIN MOLECULE
Formation of subunit of hemoglobin, calledHemoglobin chain
Formation of HEME MOLECULE
Each heme molecule combines with a long peptide chain , GLOBIN
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Hemoglobin structure
y Because each chain has a heme prosthetic group => (4) four
iron atoms in each hemoglobin molecule
y Each one can bind with 1 molecule of oxygen => making a
total of 4 molecules of oxygen (or a total of8 oxygen atoms)
that can be transported by each hemoglobin molecule
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Hemoglobin variants
y Variations in the different subunit hemoglobin chains
y Depending on the amino acid composition of the polypeptide
portion
y
Types of chains: alpha chain, beta chain, gamma chain, deltachain
y Most common form of hemoglobin in the adult human being:
HEMOGLOBIN A
y
Hemoglobin A is a combination oftwo alpha chains andtwo beta chains
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Combination ofHEMOGLOBIN with O2
y Hemoglobin combines loosely and reversibly with oxygen
y Primary function of hemoglobin in the Body: ability to
combine with oxygen in the lungs, and then release the
oxygen readily in the tissue capillaries where the gaseous
tension oxygen is much lower than in the lungs
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Combination ofHEMOGLOBIN with O2
y O2 does not combine with the two positive bonds of the ironin the hemoglobin molecule
y Instead, it binds loosely with one of the so-calledcoordination bonds of the iron atom
y Loose bond =} combination is easily reversibley Oxygen does not become ionic oxygen,but is carried as
molecular oxygen, composed of two oxygen atoms, to thetissues, where, because of the loose, readily reversible
combinationy O2 is released into the tissue fluids in the form of dissolved
molecular oxygen, rather than ionic oxygen
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Iron Storage
y Total quantity of iron in the body: averages 4-5 grams
y 65% is in the form of hemoglobin, 4% in the form of
myoglobin, 1% in the form of various heme compounds that
promote intracellular oxidation, 0.1% is combined with the
protein transferrin in the blood plasma, 15-30% is stored
mainly in the RES and liver parenchyma in the form of
FERRITIN
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Daily Loss ofIron
y Human excretes about 1mg of iron each day => feces
y Additional quantities of iron are lost whenever bleeding
occurs
y
Menstrual loss brings about iron loss of average: 2mg/day
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DESTRUCTION OF RED BLOOD CELLS
y Normally, RBCs circulate an average of 120 days before they
are destroyed == due to wearing out of life processes
y As they age, RBCS BECOME FRAGILE!!!
y
They rupture during passage through some tight spot of thecirculation as they squeeze through the red pulp of the
SPLEEN
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Normally..
yEventhough mature RBCs do not
have nucleus,mitochondria, orER
yettheyhave cytoplasmic enzymesthat are capable of metabolizing
glucose and small amounts ofATP
andNADPH
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Roles ofNADPH
y Maintain the pliability of the cell membrane
y Maintain membrane transport of ions
y Keep the iron of the hemoglobin in theferrous form (rather
than the ferric form)y Prevent oxidation of the proteins in the RBC
y * ferric form of iron causes formation of methemoglobin,
which can not carry OXYGEN
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Asthe RBCs become old
yThese metabolic systems become
also progressively less active with
timeyThe RBCs become more and
more fragile>>> presumably
because their life processes wearout
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ROLE OF THESPLEEN?
y Many of the RBCs fragment in the spleen (red
pulp), most specifically in the structural trabeculae
y WHEN THE SPLEEN IS REMOVED, THE NUMBER OF
ABNORMAL RED BLOOD CELLS AND OLD CELLS
CIRCULATING IN THE BLOOD ALSO INCREASES
CONSIDERABLY
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DESTRUCTION OF HEMOGLOBIN
y Once the RBC bursts, the HEMOGLOBIN is phagocytosed
almost immediately by macrophages
y Liver (Kupffer cells), spleen, bone marrow
y
After few hours to days, the macrophages release the ironfrom the hemoglobin back into the blood to be carried by the
TRANSFERRIN either to:
y BONE MARROW for production of new RBC, or
y
LIVER and other tissues for storage in the form ofFERRITIN
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DESTRUCTION OF HEMOGLOBIN
yThe porphyrin portion/molecule is
converted by the macrophages (thru
a series of stages) into the bile
pigment called BILIRUBIN
yBILIRUBIN is released into the blood
and later secreted by the liver into
the bile
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ANEMIASMajor classification
y BLOOD LOSS ANEMIA
usually after hemorrhage which is NOT corrected after
appropriate time
If this becomes chronic blood loss, a person frequently cannot absorb enough iron from the intestines to form
Hemoglobin as rapidly as it lost
RBCs are then produced with too little hemoglobin inside
themMICROCYTIC, HYPOCHROMIC ANEMIA
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Normal replacement
y After rapid hemorrhage, the body replaces the plasma within
1-3 days (plasma replacement)
y But this leaves a low concentration of rbcs
y
If no second hemorrhage occurs, the rbc concentrationreturns to normal within 3-6 weeks (RBC concentration
replacement)
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ANEMIASMajor classification
y APLASTIC ANEMIA
Bone marrow aplasia
Lack of a functioning bone marrow
May be due to: gamma ray radiation, excessive x-raytreatment, chemotherapeutics drugs which are suppresants
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ANEMIASMajor classification
y MEGALOBLASTIC ANEMIA
Vit B12 and folic acid deficiency, and lack of secretion of
INTRINSIC FACTOR (due to pernicious anemia) => slow
reproduction of the erythroblasts in the bone marrow
The RBCs formed are grow too large (oversized) with odd
shapes (bizzarre) megaloblasts
The RBCs formed are also fragile rupture easily
Causes: intestinal atrophy or absence of stomachdue to gastrectomy; intestinal sprue which leads to
poor absorption of important vitamins and minerals
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ANEMIASMajor classification
y HEMOLYTIC ANEMIA- shortRBC lifespan
y 1. HEREDITARY SPHEROCYTOSIS the RBCs are small
and spherical rather than being biconcave discs=> cant be
compressed because they are not loose, and are not baglike in
consistency => ruptures easily even with slightest
compression.
y 2. SICKLE CELL ANEMIA abnormal type of hemoglobin
called HEMOGLOBIN S
Leads to serious decrease of RBC mass DEATH
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HEMOGLOBINS
y When this hemoglobin is exposed to low concentrations of
oxygen, it precipitates into long crystals inside the RBC
y The crystals elongate the RBC give the appearance of beinga sickle rather than biconcave disc
y The precipitated hemoglobin also damages the cell
membrane making the RBC highly fragile
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THANK YOU
END