Transcript Lab Dx Day 1 Intro to Hematopoietic System

Intro to Hematopoietic System
Dr. Melanie Osterhouse
1040 – blood/immune
Function of blood components
 ___ - oxygen transportation (by
hemoglobin)
 ___ - mobile elements of the body’s defense
system
 ____ - cell fragments important for blood
clotting
Blood Components
Organization of Total blood volume
Blood
componenets
plasma
55%
(91% water)
WBC
(Leukocyte)
Largest
Cellular
45%
RBC
(erythrocyte)
Middle
Platelet
(thrombocyte)
Smallest
Volume of Blood
 __ L of blood circulating
 1/3 of body weight
 RBC lifetime = ____ days
 RBCs are the heaviest resulting in the
bottom layer after centrifuging
 Buffy coat - WBC and platelets - layer
above RBCs
 Plasma - on top after centrifuging
Erythrokinetics
Kidney
stimulates erythropoietin
response to low oxygen
Bone Marrow
RBC production
Lung
Oxygenation
Tissues
supplied with oxygen and nutrients
Spleen
(and liver)
destroys old RBCs
Marrow Production
 All bones - 0-5years of age
 Pelvis (40%), vertebrae (28%),
cranium/mandible (13%), ribs (8%),
sternum (2%) - 20+ years of age
 Red marrow = _____
 yellow marrow = _______
Overview of ________
number of blood cells in the blood stream depends on three
factors:
 Rate of production
 Rate of release
 Length of survival
Embryogenesis
_______________________
 3rd gestational week - stem cells in yolk sac
 3rd gestational month - liver becomes site
blood cell formation, with the help of
spleen, lymph nodes, and thymus
 4th gestational month - bone marrow
becomes functional
Location of cell line
 __________ - central marrow
 __________ - osteoid/marrow junction
 _____________ (discharge platelets) - line
sinusoids directly into blood stream
Pluripotential stem cell
terminolgy
stem cell
Stem
Cell
Lymphoid
LIne
erythroid
Non-lymphoid
line
(myeloid)
granulocyte
megakaryocyte
monocyte/macrophage
Erythropoesis
maturation process
Unipotential StemCell
(bone marrow)
Erythroblasts
6 days
Reticulocytes
(from marrow to blood)
1day:1day
Erthrocytes
120 days
Three mechanisms to increase
erythrocytes:
 Increase number of stem cells
 decrease maturation time
 release ________into the bloodstream
earlier
_________
Due to oxygen demand, erythropoetin
stimulates hastening of RBC
maturation and early release of
reticulocytes into the bloodstream
___________
 Young RBCs with extruded nucleus but
maintaining lots of RNA
 Normal reticulocyte count is 1% with an
average half-life of 4.8 hours
Reticulocytes
 The RNA is responsible for producing
_______.(RNA is not in mature RBCs)
Reticulocyte produces 30% of total hemoglobin
The other 70% is made in the pre-reticulocyte stages
 Reticulocytes have ________ receptors
Transferrin carries iron to hemoglobin-producing
immature erythrocytes
Mature RBCs don’t have the receptors due to their inability to
synthesize hemoglobin
Reticulocytes VS mature RBC
 RNA and ribosomes
 Loss or RNA and
 transferrin receptors
ribosomes
 Loss of transferrin
receptors
 No more hemoglobin
synthesis (carries
previously made Hb
from reticulocyte
stage)
bringing iron via
transferrin
 hemoglobin synthesis
____ – depression
_________ - elevation
Polycytosis – increase in RBCs
Polycytopenia – decrease in RBCs
Break down of leukocytes
WBC
leukocyte
(WBC)
agranulocyte
(mononuclear
leukocyte)
Lymphocyte
monocyte
granculocyte
(polymorphonuclear
leukocyte)
neutorophil
basophil
eosinophil
WBC
5-10,000 = normal range
granulocytes are called polymorphonuclear
due to the multilobed nucleus
leukocytes live ______ days, destroyed by
lymphatic system and excreted in feces
Function = ____________

phagocytosis

produce, transport and distribute antibodies
WBC
Differential count = number of different
types of leukocytes
________ = WBC>10,000

severe leukocytosis in:
•leukemia
•leukemoid reaction = temporary
–seen in measles, pertussis, sepsis
_________ = WBC<4000
Seen in:

infection

bone marrow disorders

hypersplenism

IDA
__________ - avoid infection


avoid contamination by fresh fruits and veggies
WBC panic values (<500 or >30,000)
WBC value variables
___________ - low in
morning and high in late
afternoon
Newborn normal (1020,000) and gradually
decreases until age 21
Differential WBC count
________ -> pyogenic infections
_________ -> allergic disorders and parasitic
infection
________-> parasitic infections
_________ -> viral infecion
__________- -> severe infections by
phagocytosis
Summary of Immune System
Immune proteins are the most diverse proteins
known.
Immune system required to survive infection
Antibodies-aka ___________
vast number of antibodies made by re-shuffling a
small set of gene fragments

Immune system
The other immune
proteins are ___ receptors
recognizes only cells that
have self and nonself
markers.

Lymphocytes
lymphocytes
Origin =bone marrow
B cells
maturation=bone marrow
memory cell
plasma cell
antibodies
immunoglobulins
T cells
maturation complete in thymus gland
cytotoxic T cells
Helper T cells
suppressor T cells
_ cell line
Antibodies mark foreign organisms for
destruction
Complement system responds to this mark by
perforating the cell membrane.
Antigen-antibody complexes attract
macrophages to engulf and digest foreign
particles
B cell line
Diversity in B cells
comes from combinational
and mutational
mechanisms
Diversity increases the
number of distinct antigen
binding sites
T cell line
________ T cell =kill
target directly
________T
cell=recognize antigen and
stimulate B and T cells
______ T cell=opposite
helper T cell.
______________ (MHC)
The third class of proteins in immune system
(B and T cells and MHC)
MHC - found on all cell surfaces
T cells require recognition of both antigen and
a self MHC protein
MHC causes T cells to be attracted to infected
cells not free bacteria (to prevent replication of
infection)
__________
Smooth discs enclosed in a plasma membrane.
Two types of granules inside:
1.alpha containing fibrinogen
2. electron dense bodies-storage site for
ADP/ATP, Ca, histamine, serotonin,
epinephrine
With injury to a vessel, platelets
undergo three reactions:
 ______- - attachment of platelets to sites of
endothelial cell injury
 __________-- release of platelet granules
– ADP induces platelet aggregation
 Platelet ___________
– Thromboxane released by platelets causing
aggregation and vasoconstriction
____________
platelet contraction - fused mass stimulated by
the combination of ADP, thrombin, and
thromboxane
Thrombin causes fibrinogen to convert to fibrin
within the platelet aggregate making “platelet
bricks”
Platelet sequence
sequence of events
endothelial injury
recognized by platelets
platelets secrete granules
synthesize thromboxane A2
activation of extrinsic coagulation sequence
due to release of tissue factor from injured cells
ADP stimulates aggregated platelets
sequence of events
endothelial injury
recognized by platelets
platelets secrete granules
synthesize thromboxane A2
activation of extrinsic coagulation sequence
due to release of tissue factor from injured cells
ADP stimulates aggregated platelets
platelet brick formed
due to deposition of fibrin
platelet brick formed
due to deposition of fibrin
Coagulation sequence
transformation of proenzymes to
activated enzymes via intrinsic and
extrinsic pathway resulting in
thrombin formation
_________
occurs on the surface of activated
platelets
____________ = reduced
platelets (normal 150,000300,000/mm3)
spontaneous bleeding occurs below
20,000/mm3 of platelets.
Post-traumatic bleeding results in
platelets in the range of 20,00050,000/mm3
Thrombocytopenia causes small
vessel bleeding m/cly. M/C sites:
 skin
 mucous membranes of GI and GU
 Intracranial bleeding
Thrombocytopenia - etiology
 Decreased platelet
production
– marrow dz
• aplastic anemia
• leukemia
– drug/ alcohol
– AIDS
• antiplatelet antibodies due
to molecular mimicry
– megaloblastic anemia
• ineffective
megakaryopoiesis
 Decreased platelet
survival
– autoimmune dz (SLE)
– drug
– Infection
 Sequestration
– hypersplenism
 Dilutional
 mechanical injury
– prosthetic heart valve
Dilutional
________ - blood stored for longer
than 24 hours has virtually no viable
platelets
Defective platelet function
_____ has antiplatelet effect and is
thus used in Tx of recurrent MI
DIC - _______________
 secondary thrombohemorrhagic disorder
 Ch. by activation of the coagulation sequence
leading to diffuse formation of microthromi
 endothelial injury - major trigger
 M/Cly seen in obstetric complications,
malignancy, sepsis, and major trauma
– malignancies include leukemiaa, CA of lung, pancreas,
colon, stomach
• tumors releasing thromboplastic substances
DIC
 deposition of fibrin within microcirculation
– causes _____-due to the squeezing of RBCs
through the narrowed microcirculation
– ischemic organs
 bleeding
– due to consumption of platelets and clotting
factors and plasminogen
DIC
 ________are found in decreasing order:
– brain, heart, lung, kidney, adrenals, spleen, liver
 50% of DIC is from complications of
________ (such as toxemia)
– reverses with delivery of fetus
Signs/Symptoms of DIC
 Respiratory
– dyspnea, cyanosis,
distress
 Neurologic
– convulsions, coma
 Renal
– oliguria, acute failure
 Circulation
– shock
 Acute DIC from
trauma or obstetric
tends to be bleeding
dominant
 Chromic DIC from
cancer tends to be
thrombotic dominant
DIC Tx
 Depends on if bleeding or thrombosis
predominates
 anticoagulants like heparin
 coagulants like fresh-frozen plasma
 Sometimes platelet transfusion
Specific anemic states
Dr. Melanie Osterhouse
Logan College of Chiropractic
____________
 Decrease in the red cells caused by too little
iron
 most common anemia
 20%women, 50%pregnancy,3%men
Risk factors for IDA
 Women who menstruate
 pregnancy or lactation
 children in rapid growth phases
 low dietary intake (no meat or egg)
 Blood loss (peptic ulcer dz, aspirin, colon
CA, uterine CA, blood donation
IDA symptoms











Pallor
fatigue
irritability
weakness
SOB
low BP
sore tongue
brittle nails
pica
decreased apetite
headache
___________
Failure of blood cell forming capacity in marrow
affecting all blood cell types
Causes Aplastic Anemia
Chemotherapy/ congenital
drugs
radiation
toxins
pregnancy
disorders
SLE
infectious
hepatitis
idiopathic
Aplastic anemia symptoms
 Fatigue
 pallor
 SOB
 tachycardia
 arrhythmia
 rash
 bruising/bleeding
Signs
 Enlarged spleen
 tender sternum
 low Hb and hematocrit
 low retic
 low platelet
 abnormal marrow biopsy
Tx
 Bone marrow transplant
 transfusions
 prognosis is death without treatment
Complications
 Infection
 cerebral hemorrhage
 bleeding
Causes of ____________
 Alcohol abuse
 Liver dz (defective
 folate or B12 def
DNA synthesis with
accelerated
erythropoiesis)
 bone marrow disorders
 hypothyroidism
 chemotherapy/drugs
 hemolysis/bleeding
macrocytosis results from:
Erythropoietin-mediated acceleration of
erythrocyte production, cell wall synthesis defects
and aberrant responses to erythropoietin
stimulation
symptoms
 Anorexia
 Headache
 diarrhea
 glossitis
 paresthesia
 jaundice
 pallor
 fatigue
__________ causes
polyneuropathy, myelopathy and
altered mental state due to:
Damage in the dorsal and lateral
columns of the spinal cord
signs
 Abnormal reflexes
 decreased
proprioception and
vibration
 low hematocrit with
high MCV
 low B12
 Elevated ferritin
Tx of B12 def
 Intramuscular B12 injections
 Normal hematology in 2 months
 Neurological compromise can be permanent