Module 2 - Anemia(s) Flashcards
Define Anemia
Reduction of the total NUMBER of erythrocytes in the blood
OR
a reduction in QUALITY or QUANTITY (ie. structure/function) of haemoglobin.
Define Polycythemia
Erythrocyte NUMBER or VOLUME are excessive
4 Things that result in Anemia
(1) Blood loss
(2) Decreased Production
(3) Increased destruction
(4) Combination of all
Anemias classified by
(1) Cause (ie. iron deficiency anemia)
(2) size, shape, content of haemoglobin (ie. Microcytic -hypochromic anemia)
The result of Anemia is
Reduced oxygen carrying capacity of the blood
What happens to the blood with a reduction of RBC
Initial Compensation
Change in blood CONSISTENCY and VOLUME
(1) Movement of interstitial fluid into the blood, increase PLASMA VOLUME
(2) Decrease VISCOSITY
Compensation for Anemia involves which 3 sytems
(1) CARDIOVASCULAR (heart)
(2) RESPIRATORY (lungs)
(3) HEMATOLOGICAL (blood)
What is Normocytic-Normochromic Anemia
NORMAL erythrocyte size
NORMAL hemoglobin concentraiton
List the 5 types of Normochromic-Normocytic Anemia
(1) Aplastic Anemia (erythropoiesis)
(2) Post hemorrhagic Anemia (blood loss)
(3) Hemolytic Anemia (lysis)
(4) Sickle Cell Anemia (genetic)
(5) Anemia of Chronic Disease (increase demand)
Mechanism of Action, and Cause
Aplastic Anemia
(1) Insufficient erythropoesis
(2) Depressed stem cell proliferation
Mechanism of Action, and Cause
Posthemorrhagic Anemia
MECHANISM - Blood Loss
CAUSE - Injury results in increased
erythropoesis and iron depletion
Mechanism of Action and Cause
Sick Cell Anemia*
MECHANISM - Abnormal Hgb Synthesis (HgS)
CAUSE - Congenital dysfunction of hemoglobin synthesis. Homozygous recessive. Hgb S. More fragile to lysis.
Mechanism of Action and Cause
Anemia of Chronic Disease*
MECHANISM - Increase DEMAND for hemoglobin
CAUSE - chronic infection, inflammation, malignancy (increase metabolism and oxygen demand)
Define Microcytic-Hypochromic anemia
SMALL abnormally shaped erythrocytes
SMALL hemoglobin concentration (pale)
List 3 microcytic-hypochromic anemias
(1) IRON DEFICIENCY anemia (lack of iron)
(2) SIDEROBLASTIC anemia (dysfunctional iron updake)
(3) THALASSEMIA (impaired synthesis hemoglobin)
Mechanism and Cause
Iron Deficiency Anemia*
MECHANISM
-Lack of Iron for hemoglobin production
CAUSE
- blood loss
- diet
- iron cycle
- iron metabolism
Mechanism and Cause
Sideroblastic Anemia
MECHANISM
- dysfunctional iron uptake by erythroblasts
- dysfunctional porphyrin and heme synthesis
CAUSE
- Congenital
- Acquired by toxins/Medications
Mechanism and Cause
Thalassemia
MECHANISM
- impaired synthesis of alpha / beta hemeoglobin
- increased phagocytosis of abnormal erythroblasts in bone marrow
CAUSE
- congenital genetic
List 2 Macrocytic (Magaloblastic)-Normochromic Anemias
(1) Pernicious Anemia (VitB12)
(2) Folate Deficiency Anemia
Mechanism and Cause
Pernicious Anemia*
MECHANISM - lack of Vitamin B12, abnormal DNA and RNA synthesis in erythroblasts, premature cell death
CAUSE - congenital or acquired deficiency intrinsic factor, genetic disorder DNA
Mechanism and Cause
Folate Deficiency Anemia
MECHANISM - lack of folate (coenzyme in thymine, adenine, guanine, methionine) premature cell death
CAUSE - dietary deficiency
What is the long term IMPACT of Anemia on the
CARDIAC SYSTEM
increased PLASMA VOLUME
decreased VISCOSITY
Blood flow is FASTER and TURBULENT
LARGER stroke volume and HEART RATE
….
CARDIAC DILATION and HEART VALVE INSUFFICIENCY if not corrected
What is the long term impact of Anemia on the
PERIPHERAL VASCULAR SYSTEM (and heart)
increased DILATION of arterioles, capillaries, venuoles (1) prevent cardiopulmonary congestion (2) meet tissue oxygen demand
increased VENOUS RETURN to the heart which increases STROKE VOLUME and HEART RATE
…
Can lead to Cardiac Failure
What is the impact of anemia on the RESPIRATORY SYSTEM
increase RATE of breathing
increase DEPTH of breathing
What are some SYMPTOMS of anemia
Dyspnea
Pounding heart beat
Pale - skin, mucous membranes, lips, nail bed, conjunctivae
Skin - Pale, loss of elasticity or Jaundice (hemolytic)
Hair - loss, grey
Nervous System (VitB12) - myelin degeneration, paraestheisas, falls, Weakness, spasticity, reflex abnormalities
GI - nausea, vomiting, anorexia
Fever - ischemic tissues release pyrogens
Define Eryptosis
Premature death of the damaged erythrocyte
List the causes of Eryptosis
(1) Dietary Deficiencies (folate, cobalamin)
(2) Infection (Malaria)
(3) Genetics (Sickle Cell, Thalassemia)
(4) Chronic Disease
Describe the PATHOPHYSIOLOGY of
Megaloblastic/Macrocytic Anemia
ASYNCHRONOUS DNA and RNA synthesis
DNA Synthesis is delayed or blocked due to lack of VitB12 or Folate
RNA Synthesis of hemoglobin is normal (Normochromic)
…
This results in an abnormally small nucleus (DNA) and abnormally large eyrhtrocyte (RNA)
What is the most common type of Macrocytic-Normochromic Anemia?
Pernicious Anemia
(lack of Vitamin B12 or Cobalamin)
Which end stage disease is associated with Pernicious Anemia
End stage Type A chronic atrophic (autoimmune) gastritis
Define Intrinsic Factor
Transporter
Required for gastric absorption of VitB12
What is the function of Vit B12
Nuclear maturation and DNA synthesis in RBC
What are 2 causes of IF deficiency
(1) Autoimmune disease directed at gastric parietal cells (secondary)
(2) Congenital - autosomal recessive inheritance (primary)
What other endocrine disorders are associated with pernicious anemia (PA)?
Polyendocrinopathy
(1) Type I diabetes
(2) Autoimmune Thyroiditis
Describe the PATHOPHYSIOLOGY of pernicious anemia SECONDARY to Type A atrophic gastritis
ANTIBODIES against the H/K ATPase results in atrophy of mucosal membrane
DISTRUCTION of parietal cells
DECREASE in Intrinsic factor production and all secretions (pepsin, HCl)
Auto-antibody NEUTRALIZE intrinsic factor
What INFECTION predisposes someone to Autoimmune
Type A Atrophic Gastritic
H. Pylori infection
antigens mimic the H/K ATPase
What are EARLY Clinical manifestations of PERNICIOUS ANEMIA
Vague
Infections
Mood swings
GI, Cardiac, Kidney problems
What are LATE clinical manifestations of PERNICIOUS ANEMIA
Classic symptoms of anemia
- weakness
- fatigue
- paraesthesia to feet and fingers
- difficulty walking
- loss of appetite
- abdominal pain
- weight loss
- sore, smooth, beefy red tongue
- lemon yellow (sallow) skin - pallor and jaundice
- Hepatomegaly (heart failure)
- Splenomegaly
What are NEUROLOGICAL manifestations of PERNICIOUS ANEMIA
NOT reversible
Demyelination of nerves resulting in neuronal death
POSTERIOR and LATERAL column of spinal cord
Loss of position and vibration sense, ataxia, spasticity
DEPRESSIVE affect (cerebrum)
What DISEASE is related to low serum VitB12
Alzheimer’s Disease
What is the TREATMENT for PERNICIOUS ANEMIA
1000mcg / day of Vitamin B12 (cobalamin)
Monthly Vit B12 injections
What is the CLINICAL INDICATOR that treatment for PERNICIOUS ANEMIA is working?
Increase in RETICULOCYTE count
Blood counts will return to normal in 5-6 weeks
How do you DIAGNOSE Pernicious Anemia
Blood Test and Serology
Gastric Biopsy (achlorhydria - absence HCl)
Antibodies against Parietal Cells and IF
What is the function of FOLATE
Folate is a COENZYME required for synthesis of thyamine, adenine, guanine (DNA nucleic acids) and methionine (amino acid)
Where do humans get FOLATE
100% from dietary intake
50-200mg/day
What populations does FOLATE DEFICIENCY occur more commonly?
Alcoholics
Chronic malnourishment
Pregnancy
What are CLINICAL MANIFESTATIONS of Folate Deficiency Anemia
Cheilosis (scale/fissure of mouth)
burning mouth syndrome (ulceration of buccal/tongue)
neurological conditions
How do you DIAGNOSE folate deficiency anemia
Blood test - serum folate levels
clinical symptoms - burning mouth syndrome
What is the TREATMENT for folate deficiency anemia
50-200 mg folate / day
Resolution 1-2 weeks
3 CAUSES of microcytic-hypochromic anemia
Disorders of….
- IRON metabolism
- HEME or PORPHORIN synthesis
- GLOBIN synthsis
What is the MOST COMMON cause of anemia world wide?
Iron Deficiency Anemia
(microcytic-microchormic)
Two different AETIOLOGIES of Iron deficiency Anemia
- NO dysfunction of iron metabolism
Ex. decreased dietary intake of iron - Dysfunction of iron metabolism
Ex. Unable to absorb to erythroblasts
Ex. Unable to transport to bone marrow
Both AETIOLOGIES of Iron Deficiency Anemia cause
- Depletion of iron stores
- Reduction in haemoglobin synthesis
How much BLOOD LOSS is required for the development of IRON DEFICIENCY ANEMIA
2-4mL per day
What are SOURCES OF BLOOD LOSS in IRON DEFICIENCY ANEMIA
Menorrhagia (excessive mentrual bleeding)
Ulcers
Esophageal varacies
Cirrhosis
Hemorrhoids
ulcerative collitis
cancer
Medications that cause GI bleeding (ASA, NSAIDS)
Procedures that speed gastric emptying
Insufficent dietary intake
Eating disorders
H. Pylori
Why does Iron Deficiency Anemia lead to INFECTIONS
Iron is involved in Cytokine activity
What groups are HIGH RISK for iron deficiency anemia
Pregnant women
Male and Female children
Women of child bearing years
Anyone at increased risk of bleeding/loss of blood
What are EARLY SYMPTOMS of iron deficiency anemia
Fatigue
Pale - conjunctiva, palms, earlobes
Shortness of breath
What haemoglobin level do individuals usually seek TREATMENT for Iron Deficient Anemia
70g/L-80g/L
What are late CLINICAL MANIFESTATIONS of Iron Deficient Anemia
STRUCTURAL and FUNCTIONAL changes in the epithelium
- Brittle spoon shaped nails (Koilonychia)
- Tongue papillae atrophy (redness and burning, bald, fissured appearance)
- Angular stomatitis (dry sore corners of mouth)
- Dysphagia (mucous and inflammatory cells at esophagus)
PHYSIOLOGICAL CHANGES (lack of iron for enzyme functions)
- gastritis
- neuromuscular changes
- irritable
- head ache
- numbness, tingling
- vasomotor disturbance
- memory loss, confusion, disorientation
How is Iron Deficient Anemia DIAGNOSED
Blood and serum tests
Ferritin level
Transferrin saturation (total iron binding capacity)
FEP (Free erythrocyte protoporphyrin - precursor of heme)
What is the TREATMENT for Iron Deficiency Anemia
- Find and correct the SOURCE (diet? blood loss?)
- Iron Replacement Therapy
- Parenteral Iron Replacement
(malabsorption, lack of adherence, chronic uncontrolled blood loss, intolerance PO)
What is the goal of SERUM FERRITIN during treatment of Iron Deficiency Anemia
50 microg/L
How long should IRON REPLACEMENT continue
6-12 months
life long for mentruating women
When will a reversal of symptoms be felt if TREATMENT is effective for Iron Deficient Anemia
1 month
What is the PATHOPHYSIOLOGY of anemia of chronic infections/inflammation/malignancies
Decrease erythropoeisis
Decreased life span of the RBC
Disruption iron cycle
What are the CLINICAL MANIFESTATIONS of anemia of chronic disease
Mild
Disease limits physical activity and demand on haemoglobin
What is the TREATMENT for Anemia of Chronic Disease
No treatment unless symptomatic
Erythropoietin
What will CLINICAL DIAGNOSTICS show of someone with anemia of chronic disease
Iron deficiency in bone marrow
Normal/high iron stores
What is the most common blood disorder in children
What is the most common cause
Anemia
Iron deficient anemia
What age does iron deficiency anemia show up in children
6 months to age 2
Why is it essential to correct anemia in children?
Irreversible changes in brain development
Iron deficiency anemia can result from
blood loss
lack of dietary intake
problems with absorption
increased requirement of iron
What clinical tests indicate iron deficiency anemia
low ferritin
low transferin
peripheral blood smear microcytic-hypochromic anemia
low hemoglobin
low haematocrit
What are the clinical manifestations of iron deficiency in children
pallor
fatigue
decreased play
irritability
ewakness
anxorexia
tachycardia
systolic murmur
widened sutures
decreased growth
developomental delay
pica
attention, alertness, learning ability (decreased)
What is Sickle Cell Anemia
Genetic autosomal recessive disorder
Genetic point mutation in Beta-Hemoglobin Glutamic Acid switched for Valine = Hgb S
What causes HgbS to Sickle
decreased oxygen, dehydration, pH trigger sickling
HgbS polymerizes resulting in sickling and hemolysis
- illness
- stress
- dehydration
- high altitude
- temperature changes
- exercise
Clinical Manifestations of a Vaso-occlusive crisis
“log jam” of sickling in microcirculation
infarction of tissues and organs
4-6 days
extreme pain
Clinical manifestations of Sequestration crisis
blood pools in spleen and liver
re-occurs
Clinical manifestations of aplastic crisis
decreased erythropoesis
Sickle cell erythrocytes only live 10-20 days
