Alterations Of Hematological Function Flashcards
Anemia
Abnormal decrease in RBCs and/or hemoglobin concentration reducing the ability of blood to carry adequate amounts of oxygen to tissues
Lab evaluation of anemia - Hemoglobin (Hgb or Hb)
Average amt of hemoglobin in a given volume of blood (g/dL)
Clinically, anemia is usually defined by a hemoglobin less than 14 g/dL in males, less than 12 g/dL in females
Lab evaluation of anemia - Hematocrit (HTC)
Percentage of a given volume of blood that is comprised of RBCs
Classification of anemia by cause - inadequate erythopoiesis
Erythropoiesis - production of RBCs in bone marrow.
Doesn’t produce enough blood in bone marrow
Classification of anemia by cause - loss of RBCs from the circulation (hemorrhage)
Blood transfusions can prevent some anemia
Classification of anemia by cause - Shortened RBC life span within the circulation (hemolysis)
RBCs are dying sooner than normal
RBCs live 120 days
Cells are lysing prematurely
Classification of anemia by cause - dilutional anemia
Not a true anemia.
Extra water or plasma that dilutes the RBCs or hemoglobin
Fluid overload
Classification of anemia by cell morphology - cell size - macrocytic
Larger than normal
Misshapen
Vitamin b12 and folic deficiency
Classification of anemia by cell morphology - cell size - normocytic
Lost a liter or two of RBCs, but cells remain normal
A cute hemorrhaging
Some RBCs may be lysed
Classification of anemaia by cell morphology - cell size - microcytic
Low iron
Low hemoglobin
Laboratory evaluation of rbc size
Mean cell volume (MCV) - average volume of the RBCs
Gives number of all RBCs and tells if its below, normal or high numbers
measured in (fL) “quadrillionth”
Hemoglobin content - normochromic
Chromic - color
Normal amt of hemoglobin would keep them normally red
Hemoglobin content - hypochromic
Pale on the inside of cells
Not as much hemoglobin
Laboratory evaluation of hemoglobin content
Mean cell hemoglobin (MCH)
CNS & musculoskeletal manifestations
Caused by decreased o2 delivery to CNS and skeletal muscles
- Fatigue and weakness
- Irritability and confusion
- Parasthesias (numbness and tingling)
Skin and mucus membrane manifestations
Pallor - pale skin, races w darker skin look inside of mucus membranes
Cardia manifestations
Caused by decreased o2 delivery to cardiac muscle
Chest pain
Heart failure
Pulmonary
Caused by hypoxia stimulation of respiratory centers in brain stem
Increased rate and depth of respirations
Dyspnea (shortness of breath) - when ruled out all other respiratory problems
Gastrointestinal
Caused by decreased o2 delivery to the digestive tract
Abdominal pain; nausea/vomiting
Decreased bowel activity
Iron deficiency anemia (IDA)
Epidemiology
Most frequently diagnosed anemia in US/worldwide
Incidence higher in females (4-6%) than males (4%)
Iron physiology - dietary sources
Meat, seafood, leafy greens, nuts and seeds, dried fruit, fortified grains/cereals
Iron physiology - absorption
In duodenum; iron absorption increased by vit C
Iron physiology - storage
Stored as ferritin in liver and bone marrow
up to 6 months of iron storage
Causes of IDA - chronic bleeding
Bleeding from gastrointestinal tract - peptic ulcer disease; gastric or colon cancer. *# 1 cause of IDA
Bleeding from urinary tract (hematuria)
Menstruation in women
Causes of IDA - inadequate dietary iron
Populations at risk
Vegetarians: unless diet includes iron-rich food or supplements
Pregnant women: increased demands on maternal iron stores
Infants fed cow’s milk: iron is in breast milk and infant formula, NOT cow’s milk
Young children: increased nutrient demand w growth, limited diet
Adolescents: growth spurts, poor diet, beginning of female menstruation
Elderly: decreased meat intake, decreased iron absorption
Causes of IDA - malabsorption of iron
Inflammatory bowl diseases (Chrons disease)
Duodenal ulcers
Patho and lab evaluation if IDA
Gradual depletion of iron stores in liver and bone marrow - decrease in plasma ferritin levels
Iron deficient erythropoiesis begins and small, Hgb-deficient RBCs enter circulation - decrease in the MVC of RBCs and decrease in hemoglobin and HCT - development of microcytic hypochromic anemia
Negative feedback to bone marrow results in decreased erythropoiesis - manifested eventually a low rbc count
Low plasma iron -> decreased production of RBCs
Vitamin b12 deficiency anemia
Vitamin b12 anemia has historically been known as “pernicious anemia”. This means destructive
Vit b12 physiology - dietary sources
Meat (especially liver and shellfish) eggs, dairy products
Vit b12 physiology - absorption
Requires intrinsic factor secreted by the parietal cells in the gastric lining
Vit b12 and intrinsic factor complex is absorbed in the lieum (distal small intestine)
Vit b12 physiology - storage
Liver is normally able to store up to 3-6 years of vit b12
Causes - inadequate intake of vit b12
Pop at risk: strict vegans who do not consume meat, egg or dairy
Increased demand for vit b12
Pregnancy - expansion of blood volume increases the demand for all nutrients necessary in erythropoiesis
Malabsorption of b12
Autoimmune antibodies to gastric parietal cells or intrinsic factor (autoimmune form of chronic gastritis)
Congenital (genetic) deficiency of intrinsic factor
Gastrectomy
Disorders of distal ileum (chrons disease)
Surgical resection (removal) of the ileum
Role of b12 and folate in erythropoiesis
Both vits are co-enzymes necessary for DNA synthesis in developing red blood cell
Patho and lab evaluation of vit b12
Vit b12 deficiency (manifested by low plasma b12 levels) results in a decrease in the rate of cell division of developing RBCs combined w normal growth rate
Schilling test for vit b12 absorption
Oral ingestion of radioactive b12 and injection of vit b12, followed by a 24-hr urine collection
Vit b12 deficiency results in the following
- Decrease in number of rbcs produced by bone marrow (low Hgb and Hct)
- Production of unusually large stem cells that mature into unusually large erythrocytes (elevated mean cell volume (MCV))
Patho of vit b12 deficiency - macrocytes
Thin, flimsy plasma membranes, rupture prematurely in micro circulation of spleen and liver (further reduces rbc count, Hgb and Hct, and presents w hemolysis)
Severe vit b12 deficiency
Results in myelin degeneration
Loss of neurons in the spinal cord
Peripheral nerve degeneration
Folate deficiency anemia physiology
Dietary sources: leafy greens, broccoli, lemons, bananas, melons, nuts, oranges, navy beans, yeast, grains, liver
Folate stores: 2-4 months in liver
Causes of folate deficiency - inadequate dietary folate or low body stores of folate *affected pops
Alcoholics: alcohol interferes w folate metabolism, depletes folate stores
Chronically malnourished
Elderly
Causes of folate deficiency - increased demand for folate
Pregnant women - can lead to neural tube defects
Children undergoing growth spurts
Causes for folate deficiency - malabsorption
Chronic malabsorption disorders (chrons disease)
Patho and lab evaluation of folate deficiency
Folate deficiency (low plasma folate levels) results in a decrease in the rate of cell division of developing rbcs combined with normal rate of growth
Same patho and consequences as vit b12 except for neurological effects
Hemolytic anemia
Premature accelerated destruction of otherwise normal erythrocytes
Causes of hemolytic anemia
Genetic defects leading to malformation of the hemoglobin or defects in rbc metabolism
Autoimmunity - immune-mediated hemolysis (idiopathic origin)
Infection (malaria, Epstein Barr virus, clostridium, mycoplasma)
Toxic/chemical injury (arsenic, lead, etc)
Many other causes including wide array of meds
Patho of immune mediated hemolysis
Binding of antibodies and complement proteins to the rbc membrane (opsonization
Opsonized rbcs are phagocytosis by macrophages as they migrate through the narrow capillaries in the spleen
Following hemolysis, excessive amts of hgb are released from rbcs and broken down by the macrophage - unconjugated bilirubin is released into the plasma
Lab evaluation and clinical manifestations of hemolytic anemia
Low hgb and hct
Elevated unconjugated bilirubin and jaundice
Elevated lactate dehydrogenase (LDH) - enzyme; in every cell; when a cell lysis it produces ldh;
Elevated reticulocyte count as bone marrow tries to compensate for the loss of rbcs
Sickle cell disease (sickle cell anemia)
Occurs in persons originating in equatorial regions (west and central africa, Middle East, Mediterranean, parts of India)
In US disease is most coming in African Americans (1/400 to 1/500 live births)
Cause of sickle cell anemia
Inherited autosomal recessive disorder - single gene (single base-pair) defects (aa)
Sickle cell trait: carrier, rarely has clinical manifestations, provides immunity against malaria
Pathophysiology of sickle cell anemia
Presence of abnormal Hgb S (instead of normal HgbA)
HgbS reacts to hypoxemia and dehydration (also low pH and body temp)
Rbc takes on a rigid, sickle shape; normal flexibility of the rbc is lost
Suckling is reversible at first, but after repeated episodes the cells are irreversibly sickled
Suckling occurs in punctuated “sickle cell crises”
Consequences of rbc suckling
Sickled rbcs lyse, leading to hemolytic anemia
Sickled cells aggregate in the capillaries and obstruct blood flow (vasoocclusion crisis)
Pooling of sickled rbcs in spleen and liver (sequestration crisis)
Aplastic anemia
Bone marrow failure associated w reduction of rbcs, WBC, and platelets
Causes of aplastic anemia - genetic disorder
20% of cases
Causes of aplastic anemia - acquired disorders; seen in adulthood
80% of cases
Autoimmune disease that targets bone marrow stem cells (50% of acquired cases)
Environmental exposure
- industrial and agricultural chems ( insecticides, fungicides, cci4, benzene)
- ionizing radiation (total body)
- infections (viral hepatitis, hiv, tb, cmv)
Pathophysiology of aplastic anemia
Reduction in number or absence of bone marrow stem cells or stem cell abnormalities
Inadequate production in rbcs, WBC, platelets
Clinical consequences and laboratory evaluation of aplastic anemia
Severe pancytopenia
Anemia (low Hgb/Hct)
Leukopenia (low white blood cell count)
Thrombocytopenia (low platelet count)
Hemostasis
Formation of a stable clot is dependent on platelet function and formation of fibrin
Platelets
Small cell fragments that arise from specialized stem cells (megakaryocytes) in the bone marrow
Platelets have a 10 day life span
When activated by endothelial injury, platelets aggregate to form a platelet plug
Overview of clotting system
Activated by injury to endothelial cells
Intrinsic/extrinsic pathway -> factor X -> factor Xa -> prothrombin -> thrombin -> fibrinogen -> fibrin
End product fibrin forms a mesh work of fibers to stabilize to blood clot
Hemophilia A (bleeding disorder)
Deficiency of clotting factor VIII
Hemophilia B
Deficiency of clotting factor IX
Hemophilia C
Deficiency of clotting factor XI
Cause of hemophilia A
X-linked recessive disorder (X’Y)
Primarily affects males (1/5000)
Females are carriers
Patho of hemophilia A
Factor VIII deficiency prevents completion of intrinsic pathway of clotting cascade
Increased risk of bleeding
- mild (6-50% clotting capability); bleeding with severe trauma or surgery
- moderate (1-5% clotting capability); bleeding w trauma
- severe (<1% clotting capability); at risk for spontaneous bleeding
Clinical consequences of hemophilia A
Prolonged bleeding times
Ecchymoses/hematoma formation
Hemarthroses - bleeding in synovial joints
Chronic anemia requiring transfusions
Immune thrombotic thrombocytopenia (ITP)
Bleeding disorder
Immune mediated platelet consumption
Pathophysiology of ITP
Antibodies (IgG) produced in response to viral infection leads to cross-sensitization of antibodies to circulating platelets with IgG binding to platelets
Virus -> plasma cells produce antibodies against virus -> antibodies cross-react with and bind to platelets
Enhanced phagocytosis of platelets by WBC in spleen
Results in severe thrombocytopenia
Polycythemia Vera (clotting disorder)
Caused by overproduction of erythrocytes (rbcs) by the bone marrow, unknown cause
Leads to increased blood coaguability and blood clotting (thrombotic) events such as deep vein thrombosis, stroke, heart attack
Disseminated intravascular coagulation (clotting disorder)
DIC is a pathological process triggered y the systemic activation of the clotting cascade with the resulting consumption of clotting factors and platelets which leads to generalized bleeding
Patho of DIC
Cycle of clotting, fibrinolysis, bleeding
Endothelial injury activated platelets and the clotting system
Small clots begin to appear in microcirulation and interfere with blood flow causing tissue and organ ischemia
Inappropriate and excessive clotting depletes available clotting factors and platelets, leads to bleeding
