Pathophysiology Module 9

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?

1. Hemoglobin → globin → amino acids

2. 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