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Anemia Definition
A condition where the body has a low level of red blood cells or hemoglobin.
How do people become anemic?
Excessive blood loss
Decreased RBC production
Increased RBC destruction
What is the composition of blood?
45% RBC → sinks to bottom of tube
Hematocrit
5 million RBC/ml
1% buffy coat
55% plasma
91% H2O
7% Proteins
2% Dissolved nutrients, small amount of electrolytes and hormones
What are the changes to hematocrit in anemia?
Noticeably lower red blood cell count than normal (<45%)
RBCs still sink to bottom of test tube but fill much fewer than half
Ex: 8 hemoglobin ; 24 hematocrit
What are the changes to hematocrit in polycythemia?
Noticeably higher red blood cell count than normal (>45%)
RBCs still sink to bottom of test tube but fill much greater than half
Ex: 20 hemoglobin ; 60 hematocrit
Polycythemia vera
The body produces excessive amounts of red blood cells.
> 45% red blood cell count
What are normal levels of hemoglobin?
Approximately 13 for both men and women
Overall range does differ between men and women
True or false: hematocrit is 5 times the amount of hemoglobin
FALSE - hematocrit is 3 times the amount of hemoglobin
What is the normal level of hematocrit?
About 39
3 times the amount of hemoglobin
If someone goes to the ER and you give them 2 liters of IV fluids instead of the 1 liter they were prescribed. What condition would you see in a blood draw?
Anemia
Less red blood cells in test tube because body water content is so high
If someone comes into the ER and is severely dehydrated. What condition would you see in a blood draw?
Polycythemia
Higher red blood cells in test tube because body water content is so low
True or false: the hemoglobin to hematocrit ratio tells you the hydration status of the patient along with how many red blood cells there may be
TRUE
If super dehydrated, hematocrit will be high (hemoglobin will be high)
If someone is retaining lots of water, hematocrit will be low (hemoglobin will be low)
What are the direct functions of the hematologic system?
Carry nutrients to cells (glucose, lipids, amino acids, peptides, vitamins)
Carry away waste from cells (CO2, breakdown of nucleic acid, Cr, nitrates)
Carry oxygen to the inside of cells
What are the supportive roles of the hematologic system?
Intracellular communication → endocrine & paracrine
Protection (defense) → cell and immunologic protein movement
Self-repair mechanism → clotting cascade
What is the shape of a red blood cell? Why?
Biconcave disc
Not round, biconcave bc it allows the disc to carry more oxygen due to greater surface area + cells float smoothly
required for oxygen and carbon dioxide diffusion
What is the unique property that red blood cells have?
Shape memory
Red blood cells can fold to fit the size of small capillaries and regain its shape back
If RBCs did not have shape memory → they would get stuck in capillaries and cause blockages/clots
True or false: mature RBCs do not have a nucleus but have mitochondria and organelles.
FALSE → mature RBCs do not have a nucleus, mitochondria, or organelles.
Packed with hemoglobin
Capable of anaerobic respiration (bc no mitochondria)
Additional information about hemoglobin
hemoglobin carries 97% of oxygen; 3% diffused in blood
3% = partial pressure of oxygen
True or false: when partial pressure drops, oxygen is released from hemoglobin to maintain the partial pressure
TRUE
PAO2 goes down → O2 saturation (O2 carried by RBCs) goes down
How tightly or loosely oxygen is bound to hemoglobin is dependent on what factor?
The shape of the hemoglobin molecule
What is a change in the shape of a hemoglobin molecule determined by?
Increased level of CO2
Decrease in pH
Carbon monoxide (high affinity to bind with hemoglobin)
Bisphosphoglyceric (BPG) chemical
Temperature
Oxygen association-dissociation curve
High oxygenation = hemoglobin almost fully saturated with O2
Low oxygenation = hemoglobin releases O2 more readily
True or false: macrophages do phagocytosis of old deformed RBCs following their 120 day lifespan.
TRUE → especially in spleen, bone, liver
What happens to the red blood cell when it is broken down by macrophages?
Hemoglobin → globin → amino acids
Hemoglobin → heme → iron & bilirubin + albumin → unconjugated bilirubin goes to liver → liver converts it to conjugated bilirubin → excreted with bile in GI tract + urine
How does the iron generated by breaking hemoglobin down into heme reach the bone marrow?
The iron is bound to transferrin → stored as ferritin → stimulates bone marrow to produce more RBCs
Transferrin: transfers iron to the bone marrow
Body likes to store excess iron as ferritin
If someone’s unconjugated bilirubin is very high, what might be the problem?
The liver is not functioning properly.
If also having high levels of conjugated bilirubin, the patient may have a large portion of their RBC count being broken down (anemia)
What will a deficiency of ferritin indicate?
The body is not storing enough iron.
Ask about patient’s nutrition → are they getting enough iron in the first place?
Is it good to have more free iron?
Free iron is a free radical that can react and damage DNA.
This is why it is stored as ferritin
Body does a poor job of excreting excess iron
How do males excrete excess iron?
Mostly through fecal matter
How do females excrete excess iron?
Through both fecal matter and menstruation (30-50 ml/cycle)
How many mg of iron does 1 ml of blood contain?
1 mg of Fe
Where does the body get iron from?
Food sources
Animal products → heme-iron
Vegetables & fruits → non-heme iron
True or false: the body has evolved to be better at absorbing the non-heme form of iron over the heme form of iron.
FALSE → the body is better at absorbing the heme-iron
What is important for proper absorption of iron?
Adequate pH of gastric acid
Where is iron absorbed by the body?
Duodenum & upper jejunum
Will a patient taking antacids during an acid-reflux spell have proper absorption of iron?
No because the antacids will neutralize the pH of the gastric acid, making a difficult absorption for iron
Patients with long-term use of antacids or PPIs tend to have iron deficiencies
What are the forms of iron supplementation?
Oral → do not take on an empty stomach (bloating, constipation, distress)
Vitamin C helps with absorption → ACIDIC so helps pH of gastric acid
What should we tell patients to take with their iron supplementation?
A glass of orange juice (vitamin C).
What could lead to iron deficiencies?
Decreased intake of Fe → poor dentures, vegetarian/vegan
Decreased absorption of Fe → celiac sprue, gastrectomy (impacts duodenum absorption), IBD, PPI or antacids
Increased demand for Fe → children, infants, pregnant, periods, lactation
Increased loss of Fe → bleeding (GI), menstruation (excessive), chronic kidney disease, GI loss, hookworm (underdeveloped countries), Peptic ulcer disease (developed countries)
What are the signs and symptoms of anemia?
Pale
Fatigue → poor oxygenation
Shortness of breath/Dyspnea
Weakness
Tachycardia → HR increases to compensate for poor oxygenation
Increased flow of circulation → RAPID BOUNDING PULSE; low viscosity = high velocity
Tinnitus → high blood velocity = ringing in ear
Vertigo
Cheilosis = cracks around lip
Atrophic glossitis = thinning of tongue with inflammation
Nails are spoon shaped → less keratin
What labs are associated with anemia?
Hemoglobin
What is the normal level of hemoglobin?
Males = 14-16.5
Females = 12-15
When can hemoglobin be low or high?
Anemia
Artificially low for high amount of fluid infusion
Artificially high due to low fluid levels (dehydration)
What is the normal level of hematocrit?
Males - 40-50%
Females - 36-47%
Mean Corpuscular Volume (MCV)
The volume inside the red blood cell.
Immature RBC will have higher MCV
Mature RBC will have lower MCV
What is the normal level for mean corpuscular volume (MCV)?
normal = 80-100 fL ; 1 fL = 10^-15 L
Red cell differentiation width
Not every red blood cell is the same size.
All normal RBC = 11.6-14.6%
Mean corpuscular hemoglobin (MCH)
A measure of the average amount of hemoglobin in each red blood cell.
Normal level = 27-33 picograms
Mean corpuscular hemoglobin concentration (MCHC)
Amount of hemoglobin relative to the size of the red blood cell.
Normal level = 33-36 g/dL in adults
Bone marrow house
Houses all cells except t-cells, works to make them more differentiated (mature).
What is the average lifespan of RBCs, platelets, and WBCs?
RBC = 120 days
Platelets = 8-10 days
WBCs except lymphocytes = 2-3 days
True or false: immature cells are smaller in size.
False → immature cells are larger in size.
As cells mature their proliferative capacity is reduced and their differentiation capacity is increased
Why are mature cells more condensed in size?
The nucleus is initially open with the chromatin staying loose. They become condensed and are eventually lost.
Cytoplasmic Maturation
As the cytoplasm matures, the color of the RBC in the presence of an adequate number of hemoglobin chains changes the RED
What is needed for DNA replication and proliferation?
Vitamin B-12 + Folic acid → replication and proliferation in RBCs
In the absence of Vitamin B-12 and folic acid, what happens?
The chromatin is not condensed but replication is continued → cells remain bigger (immature)
Body will kill these cells before 120 days (may lead to anemia)
True or false: only looking at hemoglobin will inform us what type of anemia a patient has
FALSE → we need to consider other tests
What test confirms Vitamin B-12 and folic acid deficiency anemia?
MCV → high MCV indicates a higher volume inside the RBC and immaturity.
If the MCV is over 100, what type of anemia should we always consider?
Vitamin B-12 and folic acid deficiency anemia
Because the RBCs remain immature so the cell will be larger.
What is the purpose of Vitamin B-12 and folic acid?
DNA maturation
Vitamin B-12: used for production of myelin
True or false: folic acid affects all cells that are rapidly proliferating
TRUE
This is why pregnant women are put on folic acid
Other examples: cells in tongue, hair, GI lining
What are sources of folic acid?
Green leafy vegetables, meat, citrus foods, nuts
What can impact the absorption of folic acid?
Folate is absorbed in the upper part of the small intestine
Celiac disease, IBS, alcohol overconsumption
What are the signs and symptoms of folate deficiency?
ALL signs and symptoms of anemia
irritability, diarrhea, and a smooth tongue
What are the sources of vitamin B-12?
Meat products
What population is at a serious risk of vitamin B-12 deficiency?
Vegans and vegetarians
Can be aided with supplements, fortified cereals, injections
What is required for the absorption of vitamin B-12?
Intrinsic factors produced by the liver
What do intrinsic factors do?
Carry vitamin B-12 to the jejunum where it is absorbed
Problem with intrinsic factors seen in: bariatric surgery, H pylori, NSAID users, peptic ulcer disease
Pernicious anemia
Deficiency of intrinsic factors
How was pernicious anemia discovered?
Anemia → deficiency of vitamin B-12 → put on B-12 diet → problem of absorption? → no → lack of intrinsic factors that are needed to transfer Vit B-12 to jejunum
What is the name of Vitamin B-12 and folic acid anemia known as when MCV is over 100?
Macrocytic Megaloblastic Anemia
Between Vitamin B-12 and folic acid deficiency anemia, which is more dangerous?
Vitamin B-12
Important to the production of the myelin sheath → lack of B-12 can cause damage to brain & spinal cord
What are the specific signs and symptoms of vitamin B-12 deficiency anemia?
difficulty in proprioception, concentrating and sluggish responses, brain fog
neuropathic pain
pins and needles sensation in fingers or toes
unsteady gait, clumsiness, loss of sensation in the feet
personality or memory changes
If a question asks you based on signs and symptoms presentation of anemia of MCV >100 is vitamin B-12 or folic acid deficiency and it shows nervous system-related issues, what should you pick?
Vitamin B-12 deficiency anemia
Chronic Bleeding - what does the body do?
The body has to deal with stored iron levels
Iron levels decrease → decreased ferritin levels → decreased serum iron levels
Body wants to transfer more iron to the bone marrow (to make RBCs)
Bone marrow will hold on to RBCs for extra time (they get smaller + even more mature) while waiting for the transferrin to bring iron → microcytic
These smaller cells with a decreased concentration of hemoglobin chains will have a faded color (hypochromic)
What is needed with chronic bleeding?
Transferrin levels must go up → TIBC (total iron binding capacity) levels go up
Why is sending iron to the bone marrow important?
For the production of red blood cells
True or false: looking under the microscope at the size of the RBC in an individual with anemia, may tell us what type it is.
TRUE
Big cell size = vitamin B or folic acid deficiency
Small cell size = iron deficiency anemia
What is the name of iron deficiency-related anemia?
Microcytic Hypochromic Anemia
True or false: hemoglobin levels will be high, ferritin will be high, and transferrin levels will be high in iron deficiency anemia.
FALSE → in iron deficiency anemia, labs will show low hemoglobin levels, low ferritin levels, and high transferrin levels.
Iron deficiency anemia
The most common type of anemia
Blood loss
Most common reason: GI bleeding
Other reasons: diet, hemorrhoids, gastritis, lead toxicity
What is a good question to as the client to diagnose chronic anemia?
Is there blood in your stool? Does your stool appear red or have a black and tarry appearance? Has your tiredness, weakness, or fatigue gotten worse over time?
Hemolytic Anemia
Breakdown of RBCs before their 120 day lifespan
Extra-corpuscular (extrinsic) → normal RBC just killing environment
Immune mediated: Rh incompatibility (wrong blood transfused), infection, drugs
Non-immune mediated: mechanical heart valve (RBCs that hit the metal mechanical heart valve causes break down)
If there is a metal object within the body, what should we be worried about?
Hemolytic anemia → RBCs aren’t meant to hit the metal surface and will break down
What is evidence of hemolysis (RBC breakdown)?
All S/S of anemia
Splenomegaly
Jaundice
dark yellow urine
Increase in LDH in absence of injury → shows cell damage
Accelerated erythropoiesis:
increase in reticulocytes (bone marrow increases RBC production but they are not fully mature)
higher MCV (bigger bc less mature)
hypochromic (paler in color)
biopsy of bone marrow identifies hypercellular bone marrow
Reticulocyte
In terms of maturation, the red blood cell that is one less immature than the most mature RBC (erythrocyte)
Normal level is 1% of blood
What are the two overarching global chain synthesis defects?
Qualitative defect (sickle cell)
Quantitative defect (thalassemia)
How many globin chains should be present?
4
Globin chain synthesis - quantitative defect (thalassemia)
There is a lack in the number of chains (<4)
Can be A chains or B chains not produced
Globin chain synthesis - qualitative defect (sickle cell disease)
There is the normal amount of chains present (4) but there is an abnormality.
Sickle cell disease
Cells have become sickled, lost their shape → hemolysis and vaso-occlusion (stick to vessels and not allow blood to flow) → ischemia and infarction
May be reversible or non-reversible
What are the main problems with sickled cells?
Hemolysis - lost shape means they are going to be broken down by the body
Lost property of shape memory - cause vaso-occlusive (sticking and prevent blood flow) disorders
What is the main symptom of sickle cell disease?
Generalized pain all over the body
What type of genetic disorder is sickle cell and where does the mutation occur?
Autosomal recessive
Mutation occurs on the 11th chromosome
What is sickle cell crisis precipitated by?
Cold, dehydration, hypoxemia, low pH
Ischemia vs infarction
Ischemia - lack of adequate amount of blood
Infarction - tissue death from lack of oxygen in blood
True or false: sickle cell anemia is only found in a particular area of the body.
FALSE - sickle cell anemia is all over the body
True or false: it is a good idea for someone with sickle cell disease to go skiing in the mountains in Colorado.
FALSE → this would create a low-oxygen environment and their body already has difficulty delivering enough oxygen, it would also be cold.
Acute Sickle Cell Disease
Severe anemia (emergency!)
Vaso-occlusive phenomena
pain (abdomen, chest, back, joints)
stroke/TIAs (mini stroke)
acute kidney injury
bone infarction
VTE
mesenteric ischemia
local tissue hypoxia
Priapism - involuntary erectile dysfunction for 4+ hours → medical emergency
Infection
Splenic sequestration (pooling of RBCs → hypovolemic shock & death)
True or false: acute sickle cell disease can become extended into chronic sickle cell disease
TRUE