McCance CH 29

Anemia

• Occurs with inadequate RBCs or insufficient RBC volume/mass.
• Polycythemia develops when RBCs are excessive.
• Can result form blood loss, impaired erythrocyte production, or increased erythrocyte destruction.
• Plasma volume changes can alter the accuracy of RBC mass measurements, with dehydration leading to relative polycythemia and fluid retention leading to hemodilution.

Classification and General Characteristics

• Anemias are classified by underlying mechanism or by changes in erythrocyte size ("-cytic") and hemoglobin content ("-chromic").
• Microcytic-hypochromic anemias are due to hemoglobin synthesis disorders, especially iron deficiency.
• Macrocytic anemias often result from hindered maturation of erythroid precursors in bone marrow.
• Normocytic-normochromic anemias have varied causes, identifiable by red blood cell shape.
• Anisocytosis means variation in size while poikilocytosis means variation in shape

Physiological Manifestations and Compensation

• Reduced oxygen-carrying capacity causes tissue hypoxia.
• Symptoms vary based on compensation ability.
• Compensation involves cardiovascular, respiratory, and hematologic systems.
• Reduced blood volume causes interstitial fluid to move into the intravascular space, decreasing blood viscosity and causing a hyperdynamic circulatory state, which increases stroke volume and heart rate.
• Chronic conditions may lead to cardiac dilation and heart valve insufficiency if not corrected.
• Hypoxemia causes dilation of arterioles, capillaries, and venules, contributing to heart rate and stroke volume increase.
• Shortness of breath, palpitations, dizziness, and fatigue can result.
• Pale skin, mucous membranes, lips, nail beds, and conjunctivae are observed in anemia.
• Hemolysis can cause yellowish skin due to breakdown products.
• Tissue hypoxia impairs healing and causes hair thinning/graying.
• Vitamin B12 deficiency can cause nervous system issues like paresthesias, gait disturbances, and weakness.
• GI issues like abdominal pain, nausea, vomiting, and anorexia can occur.
• A low-grade fever may also result from ischemic tissues.
• Severe/acute anemia triggers peripheral vasoconstriction and renal response to retain salt/water.

Interventions

• Treatment includes transfusions, dietary corrections, and supplements.
• Red blood cell transfusion is a common treatment, but patient blood management (PBM) aims to improve outcomes by effectively managing anemia and reducing blood loss.

Anemias of Blood Loss

• Can either be acute or chronic in nature

Acute Blood Loss

• Posthemorrhagic anemia is a normocytic-normochromic anemia (NNA) caused by acute blood loss.
• Primarily results in loss of intravascular volume, leading to cardiovascular collapse, shock, and potential death.
• Uncontrolled posttraumatic bleeding is the leading cause of preventable death among injured individuals.
• Volume loss reduces venous return, causing increased sympathetic activation and reduced blood pressure/cardiac output.
• If not severe, lost plasma is replaced within 24 hours, resulting in hemodilution and increased neutrophils/platelets.
• Severe loss can release immature cells.
• Reduced oxygenation stimulates erythropoietin and erythrocyte production.
• Iron recovery occurs internally, but external blood loss depletes iron stores.
• Chronic hemorrhage leads to iron deficiency anemia.
• Initial treatment involves volume restoration with intravenous fluids; large losses may need transfusions.
• Successful therapy includes returning erythrocytes to normal.
• Reticulocytes increase after 7 days.
• Normal erythrocyte count is seen at 4-6 weeks; hemoglobin restoration at 6-8 weeks.

Chronic Blood Loss

• Results in anemia only if loss exceeds bone marrow capacity to replace.
• Can cause iron deficiency anemia if iron storages get depleted

Anemia of Diminished Erythropoiesis

• Classified according to the underlying mechanism.
• Commonly caused by nutritional deficiencies, namely B12 (cobalamin), or folate (folic acid).

Megaloblastic Anemias

• Characterized by enlarged erythroid precursors and erythrocytes.
• Cells struggle to make DNA, but RNA production proceeds normally.
• Nuclear-cytoplasmic asynchrony occurs.
• Defective erythrocytes undergo programmed cell death (eryptosis) prematurely
• Vitamin B12 deficiency is caused by decreased intake, where plants and vegetables contain little cobalamin.
• Pernicious Anemia (PA) is a type of megaloblastic that is caused by autoimmune destruction of parietal cells that make intrinsic factor (IF).
• Abnormal Asynchronous maturation impacts neutrophil by tending to have giant metamyelocytes

Pernicious Anemia (PA)

• Caused by vitamin B12 deficiency (often linked to type A chronic atrophic/autoimmune gastritis).
• Autoimmune gastritis impairs intrinsic factor (IF) production, needed for B12 uptake.
• Deficiency of IF secretion can be linked to genetic components.
• Autoimmune form of the disease may have a genetic component, but no genetic pattern of transmission has been identified.
• Environmental factors (alcohol, hot tea, smoking) may contribute to chronic gastritis.
• Although PA is a benign disorder, type A chronic gastritis also puts individuals at risk for developing gastric adenocarcinoma and gastric carcinoid type I
• Autoantibodies against gastric H+-K+ ATPase are common, which leads to gastric atrophy
• T-cell response initiates gastric mucosal injury and triggers the formation of autoantibodies
• Initiation may be secondary to Helicobacter pylori infection, where antigens mimic parietal cell H+-K+ ATPase.

Pernicious Anemia (PA) - Clinical Manifestations

• Develops slowly, symptoms often go unnoticed until severe.
• Symptoms can include infections, mood swings, GI issues (nausea, abdominal pain), or ailments of the cardiac or kidney
• Classic anemia symptoms include weakness, fatigue, paresthesias, walking difficulty, appetite loss, weight loss, and a sore tongue that is smooth and beefy red due to atrophic glossitis.
• The skin may become "lemon yellow" due to pallor and icterus.
• Hepatomegaly and splenomegaly may be present.
• Nerve demyelination leads to neurologic issues like loss of position/vibration sense, ataxia, and spasticity.
• Affective disorders may manifest.
• Low B12 linked to neurocognitive disorders, even Alzheimer's.
• PA can increase gastric carcinoma risk.

Pernicious Anemia (PA) - Evaluation and Treatment

• Diagnosis focuses on clinical symptoms as well as test results, like blood and bone marrow.
• Testing can reveal megaloblastic anemia, leukopenia, low B12, high homocysteine/methylmalonic acid, and reticulocyte increase.
• Gastric biopsy reveals total achlorhydria (absence of hydrochloric acid)
• Treatment includes B12 replacement, administered via weekly injections, followed by monthly injections.
• Higher does of oral B12 administration can be beneficial

Folate Deficiency Anemia

• Folic acid deficiency triggers megaloblastic anemia with similar effects as B12 deficiency.
• Folate is essential for RNA and DNA synthesis, required for thymine and purines and the conversion of homocysteine to methionine
• Most people are dependent on folic acid intake, with absorption primarily occuring in small intestine
• Folate deficiency is more common then B12, particularly in alcholics or those with malnourishment
• Alcohol will interfere with folate metabolism in the liver
• Food fortiication is decreasing incident of deficincy

Folate Deficiency Anemia - Pathophysiology

• Impaired DNA synthesis leads to megaloblastic cells with clumped nuclear chromatin.
• Can also lead to apoptosis of erythroblasts
• Deficiency can lead to fetus neural tube defects in pregnant women
• Folate also reduces circulating levels of homocysteine, which can prevent atherosclerosis
• Deficincy is also connected to development of cancers

Folate Deficiency Anemia - Clinical Manifestations, Evaluation and Treatment

• Clinical manifestations is similar to the malnourished appearance of people with Pernicious Anemia
• Sever cheliosis, stomatitis, ulcerations of the bucal mucosa and tongue
• Burning mouth syndrome, dysphagia, diarrhea, and flatulence
• Neurologic symptoms is generally not seen in Folate deficiency anemia
• Evaluation is based on symptoms and measuring serum folate levels
• Treatment will require daily oral administration of folate preparations until levels increase,
• Folate will not prevent neurologic defecits of Vitamin B12 deficiency

Microcytic-Hypochromic Anemias

• Characterized by the abnormal small erythrocytes that contain small amount of hemoglobin
• Iron deficiency is most common nutritional disorder, followed by the Anemia.
• Iron deficiency Anemia is most common in developed and undeveloped countries
• Infants drinking cows milk is at increased risk for being deficient, along with older people on restricted diets
• Daily iron requirement is 7 to 10mg for men and 7 to 20mg for women
• CAUSES: Dietary Deficiency, impaired absorption, increased requirement, and chronic blood loss
• Clinical Manifestations is the reduction in adequate levels of hemoglobin
• Black women living in urban poverty is most at risk
• Common causes of IDA is continuous blood loss via menstruation, which can be a cancerous lesion

Iron Deficiency Anemia - Pathophysiology and Clinical Manifestations

• Iron Deficiency Anemia is a hypochromic-microcytic anemia.
• Imbalances causes iron to not go to bone marrow, resulting in iron deficiency or impaired iron use
• With adequate dietary intake or blood loss, metabolic dysfucntion will occur.
• Iron contribute to immune function
• Demand for iron exceeds supply from blood loss

IDA comes in 3 stages

• Stage 1 the bodies iron storage is depleted
• Stage 2 transportation for iron to bone marrow is diminished
• Stage 3 the depleted cells enter circulation
• Early symptoms is non-specific, and includes fatigue, weakness, shortness of breath, and pale earlobes/palms/conjunctivae
• structural and functional changes will start to happen as the condition develops. Ex fingernails that become brittle, thin, and spoon-shaped.
• Also associated with burning mouth syndrome, glossitis (sore and enflamed tongue), and dryness at the corners of the mouth

Iron Deficiency Anemia - Evaluation and Treatment

• Starts from a clinical symptoms stand point, with decreased levels of hemoglobins, which is confirmed from iron storage that gets measured in the bone marrow via biopsy.
• The biopsy also measures for serum Ferritin levels, transferrin saturation
• treatment includes stopping blood loss, iron replacement and medication.
• Medication to help treat is rapid decrease in fatigue, lethargy and symptoms

Anemia of Chronic Disease

• Defined as mild/moderate anemia resulting from decreased erythropoiesis and impaired iron utilization.
• Can result from issues like cancer, systematic diseases or inflammation, or autoimmune diseases.
• People with congestive heart failure can be symptomatic
• initial severity is related to symptoms, with the cause lasting from 1-2 months
• Those that are older than 65 and live in nursing homes most likely will have Anemia of Chronic Disease
• They will also have inflammatory cytokine

ACD - Pathophysiology

• Will present with a combination of decreased erythrocyte life span, suppressed production of erythropoietin, an ineffective bone marrow progenitor response to erythropoietin (low iron)
• During chronic inflammation a large variety of cytokines are released by lymphocytes, macrophages, and the affected tissue
• this will result in hepcidin, which will decrease ferroportin activity and supress iron release
• Destruction will occur via eryptosis
• Normal Iron transport will decrease, due to Inflammation that increase Lactoferrin, which will lead to iron binding
• Erythropoietin Defect will result in to increase erythropoiesis, and the failure of the kindey from the chronic inflamation that will inhibit the creation of the necessary hormone
• Platelet dysfunction occur, resulting in loss of erythrocytes
• Actions from bacterial toxins may be a cause

ACD - Clinical Manifestations, Evaluation, Treatment

• Mild to moderate range, clinical manifestation occur with iron levels
• Evaluation for high body iron, but low Iron erythropoiesis, due to abnormal iron, this will result in Anemia of Chronic Disease.
• Erythropoetin levels can expect to be lower than expected for the degree of anemia.
• Individuals will show low /normal iron binding capacity, with high level of serum ferritin
• Treatment and key receptors can be effective
• Main treatment is addressing/improving the underlying chronic illness.

Aplastic Anemia (AA)

• AA is a hematopoietic stem failure or Aplasia is when the bone marrow has had a reduction in the effective production of mature cells
• This causes a reduction or absense of all the blood cell type, Anemia, neutropenia, and thrombocytopenia
• Due to its effect AA cases include that are related to an individual immune system, Chemical agents and Ionizin Radiation
• AA affects both males and females at any age, can progress rapidly
• Character lesions AA are a hypocellular bone marrow (abnormal fat marrow).
• The cause is immune response to infectious agents as genetic response

Aplastic Anemia (AA) - Pathophysiology, Clinical Manifestations

• The bone marrow is replaced with fat.
• Pathogenesis for Hypocellular has the two etiologies mechanism: Extrinsic immune mediated suppression of bone marrow progenitor cells, and an intrinsic abnormality of stem cells
• Activated T-Cells suppress HSCs
• Many will have elevations of inflammatory (Cytokines): Interferon Gama, Tumor necrosis factor.
• Some people may respond to T-Cells being activated from Pathogens, drugs, etc, which genetic response
• Many will have alterations and interaction in the gut microbiota or by immune system is hypothesized as an initial factor in the development
• Symptoms is insidious, and include Hypoxemia, pallor, hemorrhaging
• Diminished leukocyte due to both infections, leading ulcerations, splenomegaly etc

Aplastic Anemia (AA) - Evaluation, Treatment

• Diagnosis is made via blood tests and bone marrow biopsies (Yellow fat, fibrous tissues).
• The confirmation comes from if AA levels were to become abnormal with low count
• Bone Marrow and stem cell transplant, with 70-80% have a death rate
• Individuals who can't undergo marrow transplantation or are the lack of a suitable donor will need Immunosuppression and Antithymglobulin will suppress the cells destroying the marrow cells
• Drugs like Cycolsporin will suppress the activity of cells with additional of therapy produces great benefits
• Risk and factors with AA that treatment will fail, or late clonal may occur

Hemolytic Anemia

• Red Blood Cells are premature, they can occur constantly or episodically.
• Large part is in the spleen to break down (extravascluar)
• Less common is intravascular (blood vessel) breakdown.
• The consequences will be elevated levels of Erythropoetin to accelerate production of erythrocytes with elevated levels of hemolysis.
• Hemolytic Anemias are either a cause of Hereditary for Intrinsic and Acquired form

Hemolytic Anemia - Pathophysiology

• Extravascular ( outside blood ): Appears to be caused by Erythocytes change and age, from the shape.
• Intravascular ( inside blood ): is caused by destruction of erythrocytes, frequently by antibody and complement.
• Another form of distraction is mechanical jury, repetitive physical trauma, cardiac valves,
• Toxic injury from snake venom
• Paroxysmal nocturnal hemoglobinuria: Rare , its from Acquired Defects due to the breaking of erythrocytes from blood.

Hemolytic Anemia - Clinical Manifestations and Treatment

• Severity Depend on the anemia and hemolysis , that affect with the compensatory erythropoiesis.
• Increased Red cell production but unable to keep up with distraction causes the hemolysis. The more severe, the more noticeable such and that it can be found shortly after birth
• Jaundice ( Icterus ) happens when HEME distraction excess the liver of their ability to conjugate and excrete what needed.
• Treatment is finding the underline issues via steroids or surgery. Rituximab has helped treat other anemias with multiple sclerosis and it may result in complement lysis