anemia:

• reduction in the total number of erythrocytes in the circulating blood or in the quality or quantity of hemoglobin

• (causes)

  • impaired erythrocyte production

  • acute or chronic blood loss

  • increased erythrocyte destruction

  • combination of above

• classifications

  • anemias are classified in two ways

  • etiology- based on their etiology

  • morphology- morphology classification is based on two characteristics

    • size

      • cellular size is identified by terms that end in -cytic such as macrocytic, microcytic, normocytic

        • macrocytic typically results bc of a defect in dna synthesis (usually bc of b12/folate deficiencies). they are typically larger but theres less of them and they are usually immature. they also often have structural and functional abnormalities such as immaturity, fragility, and decreased numbers

    • hemoglobin content

      • hemoglobin content is identified by terms that end in -chromic such as normochromic and hypochromic

• physiologic manifestation

  • major physiologic manifestation is hypoxia (reduced oxygen carrying capacity)

• symptoms

  • symptoms vary based on severity and the ability for the body to compensate for hypozia

    • body compensation for anemia by respiratory (increased rate and depth of breathing), cv (increased heart beat (rate? bp? both?), and hematologic systems

  • classic anemia symptoms

    • fatigue, weakness, dyspnea, pallor

• anisocytosis- rbcs are present in various sizes

macrocytic-normochromic anemias:

• macrocytic (also termed megaloblastic) anemia is:

  • characterized by defective dna synthesis that results ineffective erythropoesis (large megaloblasts [large precursor (immature) cells to rbc’s, shouldn’t be in circulation] and large macrocytes [large rbc])

  • defective dna synthesis is caused by deficiencies in vitamin b12 or folate (both are needed as coenzymes for nuclear maturation and the dna synthesis pathway)

  • rna processes occur at a normal rate

  • results in the unequal growth of the nucleus and cytoplasm

    • dna synthesis being impaired causes the cell cycle/division to slow or stop but rna synthesis is continuing which directs production of proteins and other cellular components. since rna synthesis is at a normal rate while cell devision is slowed/stopped, there will be more proteins/cell components than there should be

• pernicious anemia

  • the most common type of macrocytic normochromic anemia

    • caused by vitamin b12 deficiency

    • vitamin b12 deficiency results from defective secretion of intrinsic factor from the gastric parietal cells (gastric mucosal cells)

      • intrinsic factors is an enzyme that is essential for vitamin b12 absorption

      • vitamin b12 is required for nuclear maturation of dna synthesis in erythrocytes

  • symptoms- develop slowly (20-30 yrs), typical anemia symptoms

    • neurologic manifestations results from nerve demyelination

    • others

      • loss of appetite, abdominal pain, beefy red tongue (atrophic glossitis), icterus (jaundice), splenic enlargement

  • evaluation

    • blood test, bone marrow aspiration, schilling test, gastric biopsy, clinical symptoms

      • schilling test: the administration os radioactive cobalamin and the measurement of its excretion in the urine to test for vitamin b12 deficiency

  • treatment

    • parenteral (cyanocobalamin by intramuscular injection) or high oral doses of vitamin b12

      • parenteral == med administration by a way other than digestive tract

    • untreated pernicious anemia is fatal due to heart failure

    • effectiveness of vitamin b12 therapy is measured by reticulocyte count

• folate deficiency anemia

  • absorption of folate occurs in the upper small intestine

  • not dependent on any enzyme or other facilitating factor

    • folic acid is stored in the liver

    • its essential for rna and dna synthesis within erythrocytes

  • similar symptoms to pernicious anemia except neurological manifestations are generally not seen

  • treatment requires daily oral administration of folate

  • characterized by abnormally small and pale erythrocytes (due to abnormally reduced amounts of hemoglobin)

  • results due to

    • disorders of iron metabolism

    • disorders of porphyrin and heme synthesis

    • disorders of globin synthesis

• iron deficiency anemia

  • most common type of anemia worldwide

  • caused by

    • nutritional iron deficiency (the most common cause of iron deficiency anemia is chronic blood loss; if theres chronic blood loss, its depleting the iron faster than the nutritional intake is)

    • metabolic or functional deficiency

  • progression of iron deficiency causes

    • brittle, thin, coarsely ridged, and concave (spoon shaped) nails

    • a red, sore (ex. at the corner of mouth), and painful tongue

    • other symptoms include weakness, and dyspnea

  • evaluation: decreased hemoglobin, bone marrow biopsy (to measure iron storage), serum ferrin and treansferrin

  • treatment

    • identify and eliminate the cause, such as blood los

    • iron replacement therapy

normocytic-normochromic anemias:

• characterized by rbcs that are relatively normal in size and hemoglobin content but insufficient in number

• these anemias have no common etiology, pathology, or morphological character

• classified into

  • aplastic

  • posthemorrhagic

  • hemolytic

  • sickle cell

  • anemia of chronic inflammation

• aplastic anemia

  • pathophysiology: autoimmune disease against hematopoiesis by activated cytotoxic t cells

  • in aplastic anemia, pancytopenia (reduction or absence of all three blood cell types) develops due to suppression of the bone marrow to produce adequate amounts of erythrocytes, leukocytes, and thrombocytes

  • manifestations: related to the speed of bone marrow destruction

  • treatment: removal of cause, bone marrow and peripheral blood stem cell transplantation, immunosuppressive therapy

• posthemorrhagic anemia

  • acute blood loss from the vascular space

• hemolytic anemia

  • accelerated destruction of red blood cells

    

• sickle cell anemia

• anemia of chronic inflammation

  • mild to moderate anemia seen in

    • aids, rheumatoid arthritis, lupus erythematosus, hepatitis, renal failure, and malignancies

  • caused due to

    • decreased erythrocyte life span

    • ineffective bone marrow response to erythropoietin

    • altered iron metabolism

alterations of leukocyte function:

• quantitative disorders

  • increases or decreases in cell numbers

  • bone marrow disorders or premature destruction of cells

  • response to infectious microorganism invasion

• qualitative disorders

  • disruption of cellular function

quantitative alterations of leukocytes:

• leukocytosis

  • leukocytosis is a normal protective physiologic response to physiologic stressors

• leukopenia

  • leukopenia is not normal and not beneficial

  • a low white count predisposes a patient to infections

  • ex. neutropenia- reduction in circulating neutrophils due to

    • prolonged severe infection

    • decreased production

    • reduced survival

eosinophilia:

• hypersensitivity reactions trigger the release of eosinophilic chemotactic factor of anaphylaxis from mast cells

• increased in allergic disorders

basophils:

• basophils account for only 0-1% of the circulating wbcs

• basophilia

  • response to inflammationa dn hypersensitivity reactions

• basopenia

  • occurs in acute infections, hyperthyroidism, and long term steroid therapy

infectious mononucleosis:

• acute, self limiting infection of b lymphocytes transmitted by saliva through personal contact

• commonly caused by the epstein barr virus (ebv) - 85%

  • b cells have an ebv receptor site

• diagnostic test

  • monospot qualitative test for heterophilic antibodies

    • monospot test detect IgM

• sumptoms

  • lymph node enlargement (is a classical clinical manifestation), fever, sore throat, increased lymphocyte count, and atypical (activated) lymphocyte

leukemias:

• malignant disorder of the blood and blood forming organs

• excessive accumulation of leukemic cells

• acute leukemia

  • presence of undifferentiated or immature cells, usually blast cells

• chronic leukemia

  • predominant cell is mature but does not function normally

• early signs and symptoms of leukemias: bruising, fatigue, bone pain, anorexia

myeloma:

• proliferation of plasma cells

• the tumor may be solitary or multifocal (multiple myeloma)

• the malignant plasma produce abnormally large amounts of one class of immunoglobulin or incomplete immunoglobulin

  • the unattached light chains of the immunoglobulins (bence jones proteins) can pass through the glomerulus and damage the renal tubular cells

• multiple myeloma causes increased osteoclastic bone destruction

• clinical manifestations

  • cortical (compact bone) and medullary (spongy bone) bone loss

  • skeletal pain

  • recurring infections due to loss of the humoral immune response (humoral as in humor as in body fluid so its the fluid [blood/lymph] immune response)

malignant lymphomas:

• malignant transformation of a lymphocyte and proliferation of lymphocytes, histiocytes, their precursors, and derivatives in lymphoid tissues

• two major categories

  • hodgkin lymphoma

  • non hodgkin lymphoma

hodgkin lymphoma:

• characterized by the presence of reed sternberg cells in the lymph nodes

  • reed sternberg cells are necessary for diagnosis, but they are not specific to hodgkin lymphoma

  • classical hodgkin lymphoma

  • nodular lymphocyte predominant hodgkin lymphoma

• physical findings

  • adenopathy (swelling/enlargement of lymph nodes), mediastinal mass, splenomegaly, and abdominal mass

• symptoms

  • fever, weight loss, night sweats, pruritus (itching)

• laboratory findings

  • thrombocytosis (high number of platelets), leukocytosis, eosinophilia, elevated esr, and elevated alkaline phosphatase

    • elevated esr: erythrocyte sedimentation rate, aka how quickly rbcs settle at the bottom of a test tube, helps detect inflammation (more inflammation means more of certain proteins which causes rbcs to clump together which causes them to sink)

• paraneoplastic syndromes

• common sites of hodgkin lymphoma masses (either enlarged lymph nodes or tumors)

  • left and right axillary nodes

  • left and right cervical supraclavicular nodes

  • retroperitoneal nodes (located behind the peritoneum)

  • left and right inguinal nodes

• uncommon sites of hodgkin lymphoma masses (either enlarged lymph nodes or tumors)

  • epitrochlear and brachial nodes

  • mesenteric nodes

  • popliteal nodes

disorders of platelets:

• immune thrombocytopenic purpura (itp)

  • IgG antibody that targets platelet glycoproteins

  • antibody coated platelets are sequestered and removed from the circulation

  • the acute form of itp that often develops after a viral infection is one of the most common childhood bleeding disorders

  • manifestations

    • petechiae (tiny, pinpoint, red/purple spots on skin caused by bleeding under skin from capillaries, don’t blanch when pressed) and purpura (larger, flat, red/purple spots caused by bleeding under the skin, often from larger vessels than those causing petichiae), progressing to major hemorrhage

alterations of platelet function:

• qualitative alterations in platelet function demonstrate an increased bleeding time in the presence of a normal platelet count

• platelet function disorders result from platelet membrane glycoprotein and von willebrand factor deficiencies

• manifestations

  • petichiae, pupura, mucosal bleeding (bleeding from any mucous membrane, ex. nose, mouth, gums, gi tract), gingival bleeding, and spontaneous bruising

• disorders can be congenital or acquired

alterations of coagulation:

• vitamin k deficiency

  • vitamin k is necessary for synthesis and regulation of prothrombin, the prothrombin factors (ii, vii, xi, x), and proteins c and s (anticoagulants)

• liver disease

  • liver disease causes a broad range of hemostasis disorders

    • defects in coagulation, fibrinolysis, and platelet number/function