Module 3 Flashcards
Composition of Blood
45%RBC
50% Water
About 5% Formed Elements - Plasma Substances
Less than 1% Buffy Coat of WBC above RBC layer
Composition of Formed Elements
99% Erythrocytes
Leukocytes
Thrombocytes
Composition of Blood Plasma
-90% Water
-Plasma Proteins (Albumin, Globulins, Fibrinogen)
-Electrolytes, dissolved gasses, waste products of metabolism, nutrients, vitamins, cholesterol
Albumin
Plasma protein essential in wound healing, oncotic pressure establishment, and colloid osmotic pressure in capillary dynamics
Globulins
Plasma proteins that participate in the specific immune response. They are made by B cells/Plasma Cells
Fibrinogen
Plasma protein that is a component of the clotting cascade (through stabilizing the clots)
Examples of Waste Products in the Blood from Metabolism?
Urea
Creatinine
Pancytopenia
Anemia where a person has a low count for all 3 types of formed elements (Thrombo-, Leuko-, Erythro-)
Most abundant plasma protein?
Albumin
Kupffer Cells
Macrophages of the liver
Hematopoiesis
Production of blood elements through the differentiation of stem cells
Pluripotent “Hematopoietic” Stem cells
“Mother Cells” that are the source of ALL blood cells and are located in bone marrow
Progenitor Cell
A differentiated pluripotent stem cell that is now committed to one particular lineage of blood cell
Growth Factors
Factors stimulating the growth and differentiation of progenitor cells into one of the forms of formed elements
Erythrocyte Growth Factor
Kidney Erythropoietin
When does the kidney release erythropoietin?
When it detects low oxygen levels in blood (hypoxia, smoking, etc)
5 Types of Progenitor Cells?
Pluripotent Stem Cell –> Erythroblast, Myeloblast, Monoblast, Megalokaryoblast, Prolymphoblast
Erythroblast Differentiation Line
Erythroblast –> Reticulocyte –> Erythrocyte
Myeloblast Differentiation Line
Myeloblast –> Granulocyte –> Eosinophil, Basophil (mast cell), Neutrophil
Monoblast Differentiation Line
Monoblast –> Monocyte –> (in tissue) Macrophage
Megalokaryoblast Differentiation Line
Megalokaryoblast –> Break apart into Platelets
Prolymphoblast Differentiation line
Prolymphoblast –> Lymphoid Stem Cell –> B and T Lymphocytes –> Plasma Cell and Killer T Cell respectively
What is the main take away for cellular differentiation?
The mother cell becomes a progenitor cell that chooses a line to follow and STICKS WITH IT
Difference between Differentiation and Proliferation?
Differentiation is cell maturation and Proliferation is just an increase in cell numbers
Are growth factors specific or non specific?
Both, some act on several progenitor cells and some are for specific lines
Growth factors for specific lines of cells are called…
Colony Stimulating Factors
GCSF
- Granulocyte Colony Stimulating Factor
- GF for granulocytes
Erythropoietin
-GF for erythrocytes coming from the kidneys
Many growth factors are…
Cytokines (from the immune and inflammatory cells)
As a growth factor, Cytokines can control…
blood cell amount
RBC have no what?
Nucleus, Mitochondria, Ribosomes, Reproduction Ability
What does the shape of the RBC allow for?
The bi concave disk shape allows for a high SA to allow rapid diffusion, and with it being small and flexible allows for it to rapidly diffuse into capillary beds
Erythropoiesis
process of growth for RBC using the growth factor erythropoietin
Lifespan of RBC
120 days
Timeline of an RBC
Unipotential Stem Cell meets Erythropoietin to produce an Erythroblast in about 6 days, The reticulocyte then stays for 1 day in the marrow and then remains for a day in the blood as a nucleated reticulocyte before becoming an erythrocyte for 120 days in the blood
Building blocks of Erythropoiesis?
Iron, Folic acid, Vitamin B12
Reticulocytes in the bloodstream are important because?
They show the bone marrow is working
How are reticulocytes different from erythrocytes?
they are bigger and have part of the retained nucleus
What occurs when RBCs reach the end of their 120 day cycle?
The RBC disintegrates, releases Hgb and components into the blood circulation
What phagocytizes old RBC?
the liver and the spleen
What occurs to RBC globulin after phagocytosis?
its converted to Amino acids
What occurs to RBC iron after phagocytosis?
its stored int the liver and spleen until transferring carries it to the bone marrow to make more Hgb
What occurs to the majority of the RBC molecule after phagocytosis?
It is converted to bilirubin and excreted as bile/in urine
How do rates of destruction and synthesis relate in good health?
Rate of Destruction = Rate of Synthesis
Composition of Hemoglobin?
Heme (iron) and Globulin proteins
How many binding sites does an RBC have?
1200 (300 Hgb per molecule * 4 binding sites per Hgb)
Why are the 100 abnormal types of Hgb abnormal?
they carry O2 poorly, do not carry O2 at all, or do not survive a full 120 days
Hematocrit (Hct)
Percentage of blood that is red blood cells
What is the normal Hct value?
45%
Why is Hct not as useful?
its a percentage (relative) so an abnormality could occur with a normal Hct level
Mean Corpuscular Volume
Relates to Cell Size
> MCV = Hct/RBC
Microcytic
cells too small in size (low MCV)
Normocytic
cells normal in size
Macrocytic
cells too large in size (high MCV)
Mean Corpuscular Hemoglobin Concentration
- Weight of Hgb per volume RBCs
-MCHC = Hgb/Hct
-When we discuss this we are talking about the cell color (due to iron)
Hypochromic
cells with too little Hgb (less red)
Normochromic
cells with a normal amount of Hgb
Hyperchromic
Cells with too dense Hgb (very red)
Mean Corpuscular Hemoglobin
- Less important
-Average Hgb weight in each RBC (MCH = Hgb/RBC)
Why is Mean Corpuscular Hemoglobin less important?
it Reflects BOTH size of RBC and concentration of Hgb in the RBC (Color) so it is hard to interpret
What does a low MCH value mean?
Hypochromia OR Microcytosis OR both
Red Cell Distribution Width (RDW)
- standard deviation of MCV (Size)
-its a measure of the degree of uniformity of the RBC sizes (uniformity amongst all of them)
Exception to RDW measures?
Thalassemia
Thalassemia
- Genetic anemia for people of Mediterranean or SE Asian descent
- the RBC are a uniform cell size, but there is less Hgb leading to anemia
Key point to remember about RDW uniformity?
The cells are the same size, but the size might be abnormal
Low degree of RBC uniformity leads to…
A higher RDW value
RDW has____ sensitivity and ___ specificity
high sensitivity and low specificity
What does a normal RDW value say?
- You can rule out iron deficiency anemia since it has a high RDW (high sensitivity), but you cannot rule out anemia (low specificity)
RDW tells us about RBC size problems, but not if the mean is too low, high, or normal - to know that you must look at …
MCV (Mean Corpuscular Volume)
Reticulocyte Count
-A very important measure
- Indicates the number of RBCs containing RNA (ones that have not disposed of the nucleus entirely yet)
When you have a reticulocyte count you need to know …
if kidney function is great, because if it is bad then there is no erythropoietin
Increased Erythropoietin leads to
Increased reticulocyte amount
Reticulocyte Count is a good indicator of …
bone marrow function
Reticulocyte count is the …
-most reliable measure of RBC production (when looking at absolute rather than relative)
- Absolute = %Reticulocytes * RBC count
Spherocytes
Abnormal small and round morphology of RBC
Elliptocytes
-Abnormal Elliptical or Oval morphology of RBC
-causes more hemolysis
Sickle
Abnormal crescent morphology of RBC that clogs and can cause sickle cell crisis
Target Cell Morphology
- RBC cells that are thin with less Hgb causing it to look like a bullseye
Anisocytosis
Peripheral smear abnormality where the RBC has an abnormal SIZE due to severe anemia
Poikilocytosis
Peripheral smear abnormality where the RBC has an abnormal SHAPE due to severe anemia
Spherocytosis
Peripheral smear abnormality where RBCs have spherical cells without pallor center (pale) due to hereditary pherocytosis
Stromatocytosis
Peripheral smear abnormality where RBCs have slit like areas of central pallor rather than round due to congenital hemolytic anemia
Target Cell Abnormality
Peripheral smear abnormality where RBCs have dark centers and periphery with a clear ring in between them due to Thalassemia and hemoglobinopathies
Basophilic Stippling
Peripheral Smear Abnormalities where RBC have punctuate stippling when wright stained DUE TO LEAD POISONING!
What are the causes of anemia?
Decreased RBC, Decreased Hgb, or Decreased Hct due to:
1. Disorder in RBC production
2. Elevated Loss of RBC
3. Absence of some substrate like globulin proteins, heme, folic acid, B12, etc
What determines the symptom expression of anemia
- Duration and Severity
- Age and Health Status
Hypoxemia
manifestation of anemia due to lack of oxygen dissolved in the blood
Manifestations of Hypoxemia
Pallor
Weakness
Listlessness
Fatigue
Increased Respiratory Rate to try and compensate
Increased heart Rate (Which can lead to more issues when there is prexisting cardiovascular issues like heart failure, angina, and intermittent claudication
dizziness
palpatations
giddiness
Intermittent Claudication
No enough blood flow and oxygen to the legs due to arteries (feels better to stop doing things that increase metabolic demand and just stand in place to help blood move down)
What things determine anemia classification?
- Rate of Development
- Morphology (Shape)
- Hemoglobin Content
- Type of Defect or Etiology
Acute Anemia
severe, rapid blood loss (hemorrhage)
Chronic Anemia
gradual blood loss or other chronic condition that results in anemia
Production Defect
the bone marrow can function , so some building block necessary is missing/low
Destruction Defect
Two fold: Either bone marrow is getting destroyed or hemolysis is occurring
Normal reticulocyte counts indicate what?
a Destruction defect since production is working - a low count would indicate a production defect where we lack building blocks
Microcytic Hypochromic Anemias
Iron Deficiency
Thalassemia
Chronic Systemic Diseases
Microcytic Normochomic Anemia
Chronic systemic disease
Normocytic Normochromic Anemias
Anemia of chronic disease
Acute blood loss
Hemolytic anemia
renal failure
liver disease
hypothyroidism
sickle cell anemia
hypersplenism
aplastic anemia
Normocytic Hypochromic Anemias
Lead poisoning (plumbism)
chronic systemic disease
Normocytic Hyperchromic Anemia
Hereditary Spherocytosis
Macrocytic Normochromic Anemias
Folic Acid deficiency
Alcoholism
B12 deficiency
hypothyroidism
chronic liver disease
drug induced (chemotherapy)
Macrocytic Hypochromic Anemia
some macrocytic anemias with superimposed iron deficiency
Anemias caused by a disorder of red blood cell production is due to?
- Inadequate or inaccessible iron
-lack of folic acid OR VB12 OR globulin
-bone marrow disease like leukemia
-erythropoietin deficiency from renal failure
Most common anemia globally?
Iron Deficiency Anemia (Microcytic, Hypochromic)
Aplastic Anemia
-Anemia caused by bone marrow failure
-Production issue
-Can be due to idiopathy, radiation, chemotherapy - but generally we do not understand why
What do lab indicators show about Aplastic Anemias?
-Normocytic Cells
-Normochromic cells
-Decreased Reticulocyte count
Signs and Symptoms of Aplastic Anemia?
-Hypoxemia
-Decrease in bone marrow function (myelosuppression)
-Infection
-Bleeding
Aplastic Anemia Treatments?
-Stopping drugs and chemo therapies
- blood transfusions
-possible bone marrow transplant
Causes of Iron Deficiency Anemia?
- Decreased iron Intake
-Decreased Iron absorption
-chronic blood loss
Lab results indicating Iron deficiency Anemia?
- Microcytic (low MCV)
-Hypochromic (Low MCHC)
(low iron availability and lower Hgb production as well)
Most common anemia?
Iron deficiency anemia
Most common cause for iron deficiency anemia?
Chronic Blood los (i.e. excessive menstrual cycle loss, 75 mL blood occult loss per day due to GI bleed)
Serum Iron Test
-not very useful (influenced by many things)
this test looks at iron bound to transferrin (serum iron) - so it tells us rate of delivery to tissues, but not amount stored in tissues.
-Hemolysis, time of day, menstruation, transfusion, etc all can alter the value
Where is iron throughout the bdoy?
70% is in the Hgb of RBC, 30% is stored in tissues as ferritin and hemosiderin
Serum Ferritin Test
-Meaningful iron test
-Measures iron stores in body (ferritin is 23% of iron stored in the liver/marrow/spleen)
-The amount of ferritin directly relates to total body stores (like savings in a bank)
- blood transfusions will not affect values, but chronic inflammation will
Best marker for iron deficiency anemia?
Serum ferritin
What can falsely impact serum ferritin levels?
tissue damage leading to chronic inflammation, malignancy, or hepatitis, and Acute or Chronic illness
How fast can serum ferritin levels be fixed with supplements?
In 2-3 weeks for oral administration, 24 hours for parenteral
Transferrin
-Globulin in the blood that binds and transports iron to the bone marrow to make Hgb
-1/3 of it is bound with iron
-1 week half life
Transferrin Concentration Test
-measures concentration of transferrin in the blood which is inversely proportional to the amount of iron stored in the body
-the value comes either directly or from estimating the total iron binding capacity (TIBC)
TIBC
-Maximum iron binding capacity of Transferring and other iron binding globulins
-This is not always done because it indicates liver function moreso than iron stores
As stores of iron increase…
transferring levels decrease
Things that influence transferrin concentrations?
inflammation, loss of proteins, nutritional status, liver disease
Transferrin Saturation Test
-The percentage of transferrin and other mobile iron binding proteins that are saturated by iron
-Transferrin Saturation (%) = (Serum iron Level/TIBC) x 100%
-20-50% is normal (half bound then go to marrow)
Transferrin Saturation as A Bus Analogy
-TIBC/Max Iron Binding capacity = # empty seats
-Transferrin Saturation = # of occupied seats
- bus = transferrin
-iron = kids
-More busses on the way = low serum ferritin
Things leading to high Transferrin Saturation?
- Iron Overload
- Hemochromatosis (over absorption) - leads to liver and spleen being full so other areas get iron and are injured as a result
We can treat iron deficiency with …
Dietary iron
Amount of dietary iron and how it is absorbed?
-10-20 mg in the diet, but only 10% is absorbed in the duodenum and upper jejunum
Dietary Iron storage amount?
5001-500 mg as ferritin and hemosiderin in liver/spleen/marrow/skeletal muscles/etc
Reasons you might be losing a lot of your dietary iron?
Menstruation or Pregnancy/Childbirth
Manifestations (S/S) of Iron Deficiency Anemia
-Same anemia symptoms
-brittle spoon shaped nails
-glossitis
-pica
-web in upper esophagus (rare)
-hypoxemia
Glossitis
red, smooth, sore tongue
Pica
habitual eating of non-nutritive substances
How to treat iron deficiency anemia?
- CORRECT THE ROOT CAUSE! (e.g. bleeding)
- give ferrous sulfate dietary supplements either orally or parenteral in deep muscle
-Reticulocytosis will occur in 4-5 days, but therapy must
continue for at least 6 months to restore stores
-Transfusions when case is severe
Precautions when giving Ferrous Sulfate?
Must be given with food since it irritates the gastric mucosa, and it must be given in a liquid form through a straw since it will permanently stain teeth
Megaloblastic Anemias
-anemia where the RBC are too big (macrocytic) with an increased MCV
-due to impaired synthesis of DNA most likely from folic acid or VB12 deficiency
-Increased MCV, Decreased Lifespan and Amount
-Possible decrease in WBC, PLT, RETICULOCYTES
Vitamin B12
- Vitamin in our food supplied from meat, eggs, milk, and cheese
-Absorbed in the terminal ileum of the S. Intestine when bound to intrinsic factor from the parietal cells
-Liver is full of VB12
Intrinsic Factor
a mucoprotein secreted by the gastric mucosa parietal cells necessary for complexing with VB12 in order for absorption to occur
What does the large VB12 stores in the liver mean for anemia?
VB12 deficiency anemia (megaloblastic) will not occur for years potentially
Causes of Vitamin B12 Megaloblastic Anemia?
- Lack of intrinsic factor
-dietary inadequacy
-ileum or parietal cell defects decreasing absorption
-parasites or unusual bacteria
Serum Vitamin B12 and Folate Lab Test
- looks at VB12 and Folic acid together
- use to check for megaloblastic anemia
Interfering Factors for VB12 and Folate levels in laboratory tests?
-For VB12: increases occur in pregnancy, with use of oral contraception, high V A and C levels, smoking
-For Folate: antagonists, hemolysis, transfusions
There is not necessarily what for Folic Acid storage?
large stores like in VB12
Cobalamine
dietary form of vitamin B12
Intrinsic Factor Antibodies Laboratory Test
-checks intrinsic factor levels for VB12 transport to liver or marrow
-checks for Pernicious anemia
Pernicious Anemia
- Pernicious means Dangerous
-autoimmune
-Anemia due to either:
Type 1 Antibodies - blocks bonding of cobalamine and I factor, destruction of gastric parietal cells (in gastric area)
OR
Type 2 Antibodies - blocks binding of complex to the ileal receptors, intefering in ileal area
Causes of Vitamin B12 Deficiency
- Decreased intake (poor diet)
-Decreased Intrinsic Factor ( total gastrectomy)
-Alcohol use (poor absorption and diet/nutrition)
-Pernicious anemia
-Spruce and Celiac Disease (maladsorption)
-Ileum Resection
-Pregnancy requirements causing increased need
What do lab tests show about VB12 deficiency anemia?
-Macrocytic
-Normochromic
-Decreased VB12 levels
Signs and Symptoms of VB12 Deficiency
-typical anemia symptoms
-Hypoxemia
-insidious symptoms
-premature grey hair
-splenomegaly
-yellow blue color blindness
-low BP
-vitiligo
-lemon yellow skin color
-low grade fever
-NEUROLOGIC SYMPTOMS (parasthesias)
Parasthesias
Numbness and tingling due to neurologic issues
Vitamin B12 Deficiency Treatments
- Increase in VB12 in diet
-Parenteral vitamin B12 (to bypass the gut antibodies from pernicious anemia)
Neurologic Symptom progression for VB12 deficiency
Early - inability to do fine movements and loss of vibratory sense (2 point discirimination)
Progressive - Parasthesias, weakness, uncoordination, ataxia, personality changes
Late - incontinence, spastic paralysis, confusion, psychosis
Why is VB12 Deficiency Insidious?
symptoms occur slowly (not at least for a year)
Vitiligo
condition that causes depigmentation of sections of the skin due to autoimmune reasons
Why does VB12 deficiency cause neurologic symptoms?
because VB12 is crucial to production and maintenance of the myelin sheathe
Ataxia
uncoordinated walk
Folic Acid Deficiency Anemia
-Megaloblastic anemia due to issues with folic acid/folate amounts for Hgb/RBC production
Causes of Folic Acid Deficiency
-Decreased Folate intrake
-Alcohol Abuse
-Increased need due to pregnancy and lactation
-Folic acid antagonists
What do laboratory tests reveal during folic acid deficiency?
-Macrocytic
-Normochromic
-Decreased amounts of serum folate in the liver/tissues
Signs and Symptoms of Folic Acid Deficiency?
-Universal Anemia symptoms
-hypoxemia
- NO NEUROLOGIC SYMPTOMS
Treatment of Folic Acid Deficiency?
-increased folic acid intake
-dietary supplements
-ceasing antagonist meds like those for rehumatoid arthritis
Low folic acid levels in pregnancy lead to…
neurotube defects in child
Major difference between VB12 and Folate deficiency anemia?
VB12 has neurologic symptoms occuring
Anemia due to Blood loss
-can either by from acute or chronic blood loss
Cause of acute anemia due to blood loss
trauma, surgery, hemorrhaging
cause of chronic anemia due to blood loss
GI bleed, ulcer, menstruation
Lab results for acute anemia due to blood loss
-normocytic
-normochromic
-increased reticulocyte count
Lab results for chronic anemia due to blood loss
-microcytic
-hypochromic
-increased reticulocyte count
Signs and Symptoms of acute anemia due to blood loss
-Volume depletion
-decreased BP and increased heart rate leading to shock
Signs and Symptoms of chronic anemia due to blood loss
hypoxemia
Treatment for acute anemia due to blood loss
-Hemostasis
-oxygen
-transfusion
>anything to stop bleeding out/shock
Treatment for chronic Anemia due to blood loss
-treat the underlying cause
-iron therapy oftentimes
Chronic anemia due to blood loss is often …
iron deficiency anemia
Why do you not want to treat chronic anemia due to blood loss with blood transfusions?
It can tell bone marrow to stop working which could lead to RBC,WBC,PLT creation shutdown (pancytopenia)
Anemia of inflammation and chronic disease
- second most common cause of anemia behind iron deficiency
-Anemia where the substrates are fine leading to normocytic, normochromic (or slightly hypochromic) RBC - but their survival is shortened and cannot be compensated/treated because inflammation interferes
-Rate of Destruction > Rate of Production (imbalance)
What happens to reticulocyte count in anemia of inflammation and chronic disease?
The count is low since this anemia does not respond to any known therapy
Polcythemia
-Opposite of Anemia
-Abnormally high total red cell mass (all cell lines: so WBC and PLT too)
-2 types - Relative, and Absolute with Primary and Secondary subtypes
Relative Polycythemia
-fluid loss without cellular loss
-Loss of plasma volume leading to a high Hct (50% rather than the normal 40-45)
Causes of Relative Polycythemia
- loss of fluid but not cell loss
ex: Diarrhea, Profuse Sweating, Dehydration
Absolute Polcythemia
- increase in the actual number of RBC
-2 subtypes: Primary and Secondary
Polycythemia Vera
-Absolute Primary Polycythemia
- proliferative disorder common in men 40-60 y/o where the blood gets very viscous (and Hct can reach 80%!! - the same as in packed blood transfusions)
Secondary Absolute Polycythemia
-Chronic hypoxia leading to the kidney increasing erythropoietin levels thus causing more cells
-ex: high altitude, smoking, COPD, tumors, heart and lung diseases can cause the hypoxia
Complications due to Polycythemia
- Increased blood viscosity interfering with cardiac flow
-Hypertension
-Venous stasis
-Thromboembolism potential (leading to stroke, heart attack, or deep vein thrombosis)
Venous Stasis
-opposite of intermittent claudication
-pooling of blood in veins leading to little clots causing the legs being unable to return blood to the heart
How to treat venous stasis?
elevate legs to return blood to heart
How to treat intermittent claudication?
lower legs to help arterial problems move blood into the legs
Treatment for Relative polycythemia
fluids
Treatment for polcythemia vera
Making the blood less viscous through normal saline, medication, bone marrow transplants, drug therapy, or periodic phlebotomy
Treatment for secondary polcythemia
Oxygen at appropriate levels to stop hypoxia (be careful when dealing with a COPD patient)
