blood Flashcards
coposition of blood
55% plasma, 45% cells
hematopoiesis
the formation of blood cellular components- stem from pluripoten matopoietic stem cell- split to lymphoid stem cells and trillineage stem cells
what is Hematopoietic System
Erythrocytes (RBCs) are ideally suited for
their primary function: transport of oxygen
from the lungs into the peripheral tissues.
• Hemoglobin is a complex molecule that
consists of four globin subunits each
containing a heme group that can carry an
oxygen molecule (or carbon monoxide)
synthesis require
Hemoglobin synthesis requires iron, vitamin
B12, vitamin B6
, and folic acid.
• Red blood cells survive in the circulation on
average for 120 days.
spleen
Spleen: contains phagocytic cells that digest
main components of RBC’s and release them
for reuse or excretion
anemia
Anemia is a reduction of hemoglobin in the blood to
below-normal levels.
• Normal levels are >130 g/L in males and >115 g/L in
females. Textbook is American so its units are
lower i.e. in g/dL
• This may be associated with the following:
– Appearance of abnormal hemoglobin
– Reduced number of red blood cells
– Structural abnormalities of red blood cells
Hypoxia-lack of oxygen to the tissues
what do cell counters do and what values do they give you
Complete blood count gives you a count of all
the cells present in the sample
• This instrument is also able to give you the
characteristics of the cells that are present
• The instrument will also give a value for the
total hemoglobin present and the hematocrit
(amount of RBCs by volume) i.e. a hematocrit
(Hct) of 40%
what mesurement are made
Objective measurements of red blood cell
parameters are done with instruments that
estimate the size of red blood cells and their
hemoglobin content.
– Mean corpuscular volume (MCV)-Mean corpuscular volume (MCV) =
• <80 fL: Microcytic Anemia fL= femtoliter =10 -15 one quadrillionth of a liter
• >100 fL: Macrocytic Anemia
– Mean corpuscular hemoglobin (MCH)-• Mean corpuscular hemoglobin (MCH) =
Normal Range 28-32 pg/cell. < 28: Hypochromic
– Mean corpuscular hemoglobin concentration
(MCHC) -Normal Range 320-360 g/L
• Low values: Hypochromic Anemia !!!!!!!!!!!!!!!!!!! be able to diferentiate
anemia occurs when
Anemia may be a consequence of:
– Decreased hematopoiesis ( production) (nutrient deficiency
– Abnormal hematopoiesis (sickle cell)
– Increased loss or destruction of red blood cells
know some deseases and what they are classified under
slide 23
Decreased Hematopoiesis
Bone marrow failure
– Aplastic anemia
– pancytopenia:: lack of all blood cells in peripheral blood
– Myelophthisic anemia: bone marrow cells may be damaged or
replaced by infiltrates of metastatic tumor cells
• Deficiencies of nutrients
– Deficiency of vitamin B12 and folic acid (megaloblastic anemia)
– Protein deficiency
– Iron deficiency: most common deficiency
Abnormal Hematopoiesis
Usually consequence of genetic
abnormalities
• Sickle cell anemia: substitution of a valine
for glutamic acid at position 6 of the Beta
chain of hemoglobin
Increased Loss and Destruction
of Red Blood Cells
• Bleeding: Dilutional Anemia • Intrasplenic sequestration: hypersplenism • Immune hemolysis • Infections (malaria): parasite Plasmodium
• Normocytic, normochromic anemia: Dilutional Anemia”
Usually following massive blood loss (or surgery because they give them more fluid): because of the loss of blood
fluid shifts from interstitial to ECF fluid compartment. Within a few
weeks blood cells are replenished by bone marrow
so looks the same just diluted
• Microcytic, hypochromic anemia
– Small & pale, Iron deficiency or thalassemia (affecting synthesis of
Hb)
• Macrocytic, normochromic anemia (normal in color, but large)
Deficiency of vitamin B12 and/or folic acid also in liver disease
• Anemia’s characterized by abnormal red blood
shapes
– Elliptocytosis, spherocytosis, sickle cell anemia
hypersplenism
increase destruction of RBC and loss
aplastic anemia
A pancytopenia or generalized bone marrow failure
Two Types
1. Idiopathic (cause unknown)
2. Secondary: bone marrow suppression. Due to cytotoxic
drugs, radiation therapy or viral infection.
• . Reversible with elimination of causative agent
• depleted of hematopoietic cells and consists only of
fibroblasts, fat cells, and scattered lymphocytes
• Anemia, leukopenia, and thrombocytopenia
• Symptoms - Uncontrollable infections, bleeding tendency,
chronic fatigue, sleepiness, and weakness
iron deficiency anemia
Most common form of anemia!!!!!!!!!
• Hypochromic microcytic anemia
• Bone marrow shows normal hematopoiesis
• Etiology
– Increased loss of iron (chronic bleeding)
– Inadequate iron intake or absorption
– Increased iron requirements (childhood growth and
pregnancy)
– Iron supplements usually solves problem
megaloblastic anemia
• Caused by a deficiency of vitamin B12 or folic acid
• Deficiency of either of the two cause a delay in hematopoiesis
• Normoblasts do not mature but are transformed to megaloblasts
– Vitamin B12 deficiency
• Pernicious Anemia: Lack of the gastric intrinsic factor due to
atrophic gastritis
– Folic acid deficiency
• Inadequate intake in the diet or because of malabsorption caused by
intestinal disease
megaloblastic anemia pathology
Bone marrow – Hypercellular, numerous megaloblasts • Peripheral blood – Decreased RBC that are macrocytic • Hypersegmentation of neutrophils
Pathologic Conditions Contributing to
Megaloblastic Anemia
Vitamin Deficiency or Malabsorption •Pernicious anemia •Resection of stomach •Celiac Disease •Crohn’s disease •Parasites
pernicious anemia
subheading of megoloblastic : Lack of the gastric intrinsic factor due to
atrophic gastritis- know how to diferentiate mega and iron deficient
Megaloblastic Anemia
Clinical Features
• Fatigue, shortness of breath, weakness
• Destruction of posterior and lateral columns in
the spinal cord—results in a loss of the senses
of vibration and proprioception, as well as loss
of the deep tendon reflexes
• Treatment Vitamin B12 injections or folic acid
supplementation.
Hemolytic Anemia
• Increased red blood cell Destruction (hemolysis)
• Intracorpuscular defects
– Structural abnormalities
Sickle cell anemia, thalassemia, or hereditary spherocytosis
• Extracorpuscular defects
– Antibodies, infectious agents, or mechanical factors
– Autoimmune hemolytic anemia, hemolytic disease of the
newborn, transfusion reactions, malaria, hemolytic anemia
caused by cardiac valve prosthesis, disseminated
intravascular coagulation
sickle cell anemia
Pathogenesis
Substitution of glutamic acid by valine in chain
• Synthesis of an abnormal beta chain of globin
• HbA gets mutated to HbS
• Low O2
tension causes deformities (sickling)
• Hemolytic crisis (avoidance of strenuous exercise)
• Aggregates cause tissue ischemia
sickle cell anemia does what
Multiple infarcts in various organs Neurologic defects; sharp pain in the bones, spleen (autosplenectomy), and extremities; retinal infarcts Hyperbilirubinemia and jaundice (bile stones). No definitive therapy, high mortality. Avoid conditions that cause sickling and combat infections
clinical features of sicke cell anemia
• Retarded intellectual development and neurologic deficits (TIAs, small infarcts, stroke) • Cardiopulmonary insufficiency (HF, MI, Pulmonary edema and PE) • Recurrent infections • HbS< 40% asymptomatic • HbS 40-80% mild to moderate disease • HbS>80% typical symptoms of disease • High mortality
thalassemia
Prevalent of people of the Mediterranean
• Genetic defect in the synthesis of HbA that reduces the rate of globin
chain synthesis
• No abnormal hemoglobin produced
• Quantitative rather than qualitative (rate of synthesis of normal is slower than we need it to be- so no abonormalities just lack of)
• beta-Thalassemia—reduced synthesis of the beta chain of globin
• alpha-Thalassemia—reduced synthesis of the alpha chain of globin
• Thalassemia minor or thalassemia trait
– Heterozygotes
– Only one of the 4 chains is missing
– Mild, nonspecific symptoms
– Microcytic Hypochromic anemia
– Requires no treatment
b- thalassemia
lack of Hba and get Hbf (a lot)- spleen breakdown more RBC causes jaundice, large speen, inlarge liver, hemosideration, growth retardation , cardiorespiratory insufficiency
thalassemia major
Thalassemia major
– Homozygotes
– Severe and serious disease
• Splenomegaly, hemosiderosis, and hepatomegaly
• Bone marrow—compensatory hyperplasia
• Calvarium—“crew-cut” hair on radiographic study
• Hyperbilirubinemia and jaundice
• Chronic anemia that retards the growth of children
• Impairment of normal intellectual development
• Cardiorespiratory insufficiency
• No treatment for thalassemia
mEDETERANIAN
Hereditary Spherocytosis
• The primary defect in the genes encoding either
ankyrin or alpha or beta chain of spectrin
• The most common hereditary disease of red blood
cells in Caucasians
• Autosomal dominant disease
• Peripheral blood—spherocytes, anisocytosis
• Hemolytic or aplastic crises—splenomegaly, jaundice
• Splenectomy- treatment but no cure- SPLEEN SEES ITS TOO SMALL SO DESTROYS THEM - hyperspleenism
Polycythemia
Erythrocytosis
• Increased number of red blood cells
• Primary polycythemia, or polycythemia vera
– Clonal proliferation of hematopoietic stem cells
– Uncontrolled production of red blood cells and an increased total red
blood cell mass
– Myeloproliferative disorder
• Secondary polycythemia
– Increased red blood cell volume owing to erythroid bone marrow
hyperplasia caused by erythropoietin
– Usually caused by prolonged hypoxia
– Living at high altitudes, anoxia secondary to chronic lung disease,
congenital heart disease, renal carcinoma-
• Primary polycythemia, or polycythemia vera
Clonal proliferation of hematopoietic stem cells
– Uncontrolled production of red blood cells and an increased total red
blood cell mass
– Myeloproliferative disorder
• Secondary polycythemia
– Increased red blood cell volume owing to erythroid bone marrow
hyperplasia caused by erythropoietin
– Usually caused by prolonged hypoxia
– Living at high altitudes, anoxia secondary to chronic lung disease,
congenital heart disease, renal carcinoma
symptoms of polycythemia
Hypertension • Dark red or flushed face • Headaches, visual problems, neurologic symptoms • Splenomegaly • Hypercellular bone marrow seenin smokers too
Leukopenia
• Reduction in white blood cell count to belownormal
levels
• Neutropenia (agranulocytosis)
– Bacterial infections
• Lymphopenia
– Bacterial, viral, fungal, and parasitic infections
Short-term treatment is with antibiotics
(fatigue, light headed)
know diferences in R AND wbc deseases
know
Leukocytosis
• Increased number of white blood cells in the
peripheral blood
• Granulocytosis, or neutrophilia
– Bacterial infection
• Eosinophilic leukocytosis, or eosinophilia
– Allergies and some skin diseases or parasitic infections
• Lymphocytosis
– Viral infections, chronic infections, some autoimmune
disorders
– Splenomegaly (septic spleen), lymphadenopathy
(enlarged)
• Granulocytosis, or neutrophilia
– Bacterial infection
• Eosinophilic leukocytosis, or eosinophilia
– Allergies and some skin diseases or parasitic infections
deferentiate leukopenia and leukocytosis
know
Lymphocytosis
– Viral infections, chronic infections, some autoimmune
disorders
– Splenomegaly (septic spleen), lymphadenopathy
(enlarged)
Malignant Diseases of
White Blood Cells
leukimia and lymphoma and multiple myeloma
leukimia
s—malignant disease involving white blood cell precursors in the bone marrow and peripheral blood (acute and chronic) – Myeloid – Lymphoid lymphocytic
Lymphomas—lymphoid
—lymphoid cell malignant diseases
predominantly involving the lymph nodes
– Non-Hodgkin’s lymphoma
– Hodgkin’s lymphoma
multiple myeloma
malignant disease of plasma
cells
Etiology and Pathogenesis
of lymphomas and leukemia
The causes of most lymphomas and leukemia’s, like
the causes of most other malignant tumors, are
unknown.
• Viruses
– HTLV-1 (Human T-Cell leukemia virus 1)
– EBV (Epstein Barr Virus)
• Endogenous oncogenes
– t(8 (is translocated to chromosome 14) ,14)—Burkett’s lymphoma
– t(9,22)—chronic myelogenous leukemia (Philadelphia
chromosome)
Leukemia
Bone marrow is infiltrated with malignant cells.
• Peripheral blood contains an increased number of
immature blood cells.
• Complications include anemia, recurrent infections,
and uncontrollable bleeding.
• 85% of all leukemia’s affect children and are acute
• Chronic leukemia’s found mostly in adults
Acute Lymphoblastic Leukemia
• Most common form of leukemia in children< 5yrs
most common leukemia in kids
• Massive infiltration of the bone marrow and peripheral blood with
immature lymphoid cells (blasts)
• 20-30% of all leukemia’s
• Recurrent infections, generalized weakness, and bleeding into the skin and
major internal organs
• Enlarged lymph nodes and mild splenomegaly
• Treatment—with modern chemotherapy, remission can be induced in 2/3
of all patients
• Without chemotherapy it is lethal within 3-6 months
list the 4 leukemias:!!!!
Acute Lymphoblastic Leukemia.
Acute Myelogenous Leukemia
Chronic Myelogenous Leukemia
Chronic Lymphocytic Leukemia
Acute Myelogenous Leukemia
This is the most common form of acute leukemia in adults.!!!!!!
• Has an acute course; without treatment patients die within 6
months of onset of symptoms
• Chemotherapy can induce remission in 60% of patients
• 15-30% remain disease free for 5 years
• High dose irradiation + chemotherapy followed by bome
marrow transplantation during the 1st remission have a 70%
3-year survival.
Chronic Myelogenous Leukemia
Malignant disease of pluripotent hematopoietic stem cells
capable of differentiating into neutrophils (alll cell lines are affected)
• Bone marrow and peripheral blood overgrown with malignant stem cells and their
descendants
• 15% of all leukemia’s: Slow onset
• Disease of adulthood, anemia and hypermetabolism (tired and prone to infection)
• Three phases of the disease:
– Chronic phase: (2 to 3 years) <10% bone marrow blasts
– Accelerated phase: >10% bone marrow (nonfunctional) blasts & >20% basophils in peripheral
blood; increasing unresponsive to therapy
– Blast crisis:> 20% blast in bone marrow
• Tyrosine kinase inhibitors: induce remission in 90% of patients (!!!!!!)
• Philadelphia (Ph1) chromosome, with BCR/ABL gene rearrangement
lymphona
It affects any age group.
• All forms are malignant
• Malignant cells often infiltrate the lymph nodes, spleen,
thymus, or bone marrow, but they may also involve any other
organ in the body.
• Extranodal lymphoma: originating outside of lymph nodes; in
solid organs, GI, brain, eyes and skin
• There are two large categories:
– Non-Hodgkin’s lymphoma (NHL)
– Hodgkin’s lymphoma
know the names, the age catagory, the symptoms, the treatments
hi
bening
its not harmful- hasnt mastatised to the blood stream
malignants
attafhes to base membrane of the cell to the blood stream and spread and some go to specific organs, example prostate- goes to brain
Non-Hodgkin’s Lymphomas
• Two major categories B and T cell neoplasms and
NK- cell neoplasms
• Most have the B cell phenotype
• Occur in all age groups but most common in adults
• Malignant cells Can spill over into blood and present
as leukemia
• Involve lymph nodes, bone marrow, spleen and thymus
but can also be Extranodal
• Most common site of Extranodal is GI
• Clinical features: lymph node enlargement;
splenomegaly and lymphocytosis (increase)
• fatigue, fever, weight loss, anemia, leukopenia
infections
what are the 2 types of lymphomas
non and the hogkins lymphomas
Follicular Lymphoma
( non hogkins lymphomas)
This is the most common form of lymphoma in the
United States (45% of all lymphomas).
• It is mostly seen in older people.
• The tumor is slow growing.
• Most patients present with long-standing enlargement
of the lymph nodes and only mild symptoms.
• Most patients survive 7 to 9 years after diagnosis of
the disease.
Diffuse Large-Cell Lymphomas
This is the most common aggressive form of NHL.
• Complete infiltration of large lymphoid cells that
have irregular outline and prominent nuclei
• Tissue is infiltrated with large lymphoid cells that
have irregular nuclear outlines and prominent
nucleoli.
• Spread to major organs is common
• With chemotherapy, complete remission can be
induced in 75% of patients.
Burkitt’s Lymphoma
• This is a highly malignant tumor composed of small B cells.
• Extranodal masses are often more prominent than enlarged lymph nodes.
• Endemic variant:
– Sub-Saharan Africa
– Children infected with Epstein-Barr Virus (EBV)
– Mandible and facial soft tissue involvement
• Sporadic variant:
– Children and young adults most often affected
– Abdominal mass (e.g., ovarian or intestinal mass)
• Most children and young adults can be cured.
• Adriamycin and rituximab — a potent chemotherapy regimen given in the
hospital about every three weeks.
Hodgkin’s Lymphoma
A form of malignant disease that is pathologically distinct from other
lymphomas
• Disease spreads from one set of lymph nodes to another
• Usually central lymph nodes
• Age distribution curve is bimodal, with one peak at 25 years and another at
55 years.
• Classical Hodgkin’s Lymphoma; Reed-Sternberg Cells are present
(Bilobed or multilobed nucleus and prominent nucleoli surrounded by a
clear halo (derived from B lymphocytes)
• Non Classical Hodgkin’s Lymphoma: Lymphocytic Cells with Popcorn
Nuclei:
what are Reed-Sternberg Cells
s are present
(Bilobed or multilobed nucleus and prominent nucleoli surrounded by a
clear halo (derived from B lymphocytes)- present in hodkin lymphomas!!!!!!!
where are popocorn cells seen
NON classical hodkins lymphomas
classical
reed-sternberg
Hodgkin’s Lymphoma
Lymph nodes are enlarged (neck and mediastinum).
• Extranodal involvement and leukemic spread are rare.
• Prognosis of the disease depends primarily on the
clinical stage.
– Stage I and II tumors are associated with an excellent
prognosis and a high rate of cure (>90%) with
chemotherapy.
– Advanced disease has a less favorable prognosis.
stage 1 Staging of Hodgkin’s Lymphoma
1: involvement of single lymphnode, 2È 2 or more site
3: deseases on both sides of daiphragm may include spleen or localized
4: widespread liver bone marrow, skin, lung
multiple myeloma
Most patients older than 45 years of age
• Malignant plasma cells typically proliferate in the
bone marrow and destroy the surrounding bone (bone
fractures)
• Hypercalcemia
• Renal failure
• Anemia and leukopenia
Malignant Disease: transformation of a single plasma cell
• Clonal expansion leads to an overgrowth in bone marrow
• Because theses cells are descendants from a single cell they are termed
“monoclonal”
• Plasma cells secrete immunoglobulins which can be detected in the serum
• After malignant transformation of a single plasma cell the descendants of this
malignant cell all secrete the same form of immunoglobulin
• Diagnosis is based on the following:
– X-ray studies (lytic lesions)
– Serum electrophoresis (monoclonal spike)
– Bone marrow biopsy (neoplastic plasma cells in increased numbers)
– Bence Jones Protein in urine (first biochemical tumor marker)
• Most patients die within 3 to 4 years, primarily of kidney failure or infection
Most patients> 45 years
• Malignant cells destroy
bone marrow
• Punch holes through blood
forming bones
• Hypercalcemia with
deposition in the kidney
• Chemotherapy ineffective
• secondary Raynauds
syndrome
what is the bence jones protein
– Bence Jones Protein in urine (first biochemical tumor marker)
bone abnormalities
crue cut- thalasemia- dont confuse with bone leision of multiple myeloma
beta
medeteranina
hyper spleenism
increase rate of loss or destruction
