Unit 3: Hematopoietic Function

serum ferritin

reflects total body iron stores, except in the presence of liver disease or acute inflammation

basophils

release histamine and mediators -occur during hypersensitivity reactions

Stages of Hodgkin's Lymphoma

stage 1: single lymph node affected stage 2: two+ lymph node regions on the same side of the diaphragm stage 3: lymph node regions on both sides of diaphragm stage 4: disseminated involvement of one or more extralymphatic organs

Mean Corpuscular Volume (MCV)

the average volume of a RBC -used for classification scheme of anemia based on size 1. normocytic anemia- 80-100 um3 (sickle cell anemia, aplastic anemia) 2. microcytic anemia - < 80 um3 (iron deficiency, thalassemia) 3. macrocytic anemia- >100 um3 (vit b12/folate deficiency anemia)

hematocrit

the ration of RBC mass to that of whole blood expressed as percent -normal 45% Rule of 3: 1. HB x 3 should approximate the hematocrit -hemoglobin of 9gm/dl = 27% hedmatocrit 2. each unit of transfused packed RBCs, the hemoglobin should increase by 1, and 3% hematocrit -e.g. hemoglobin 5 and transfused 3 units, hemoglobin should be 8 and hematocrit 24% 3. lack of an approximate increase in hemoglobin/hematocrit is most commonly due to a GI bleed

myelodysplastic syndrome

-group of hematopoietic neoplasms -result in abnormal cell growth, differentiation, and maturation -1/3 develop acute myeloid leukemia (AML) -7/100,000 people -typical age onset 70yo -somatic mutation-mutations in the multipotent myeloid progenitor cell clinical manifestations: -asymptomatic or related to certain type of cytopenia Dx: -complete Hx and PE -prognosis estimating systems TX: -observation and supportive care -hematopoiesis growth factors -chemo -stem cell transplant

what causes RBC production?

-hypoxemia and blood loss as stimuli -erythropoietin -vitamin b12 and folic acid for DNA synthesis -iron for the heme

low volume, microcytic anemias

-iron deficiency -thalassemia -lead poisoning

eosinophils and basophils

-lower in number than neutrophils

megaloblastic anemia

-macrocytic -vitamin b12 and folic acid deficiencies -impaired DNA synthesis of b12 and folic acid -causes large developing cells

leukostasis

-manifestation in leukemia -abnormal intravascular leukocyte aggregation and clumping often seen in leukemia patients -describes extreme elevation (>100,000/ul) in circulating blast (immature) cells and impaired circulation -it is dangerous because it can cause heart attacks and strokes by blocking arteries -presents with headache, confusion, dyspnea -medical emergency

anemia lab tests

-mean corpuscular volume -hematocrit -Hb electrophoresis -reticulocyte count -serum ferritin -serum iron -transferrin -transferrin saturation -Total iron binding capacity (TIBC)

thrombophilia

-State of increased coagulation -Abnormality leading to tendency to form venous thromboembolism Causes: Congenital or Acquired Congenital type: Factor V Leiden, antithrombin III deficiency, protein C deficiency and protein S deficiency Acquired type: Antiphospholipid syndrome (caused by antibodies against constituents of the cell membrane), Sickle cell dx, Polycythemia. Development of clot from inciting or prothrombotic state There is no specific treatment for thrombophilia Treatment dependent on risk for thrombosis Anticoagulation medications: •Warfarin for long-term

Leukemias

-a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells -the exact cause of leukemia is unknown -a combination of genetic and environmental factors Risk factors: -chemicals, viruses, radiation, smoking, prior chemo, and certain diseases (e.g. down syndrome) Grouped on basis of cell line -acute: rapid onset and progression -chronic: insidious onset and less aggressive Four common types: -acute lymphoblastic leukemia (ALL) -acute myeloid leukemia (AML) -chronic lymphoid leukemia (CLL) -chronic myeloid leukemia (CML) acute leukemias affect more children and elderly -short and drastic course chronic leukemias -more mature cells, midlife age range -longer, less devastating course

Chronic myelogenous leukemia

-a type of myeloproliferative neoplasm associated with a characteristic chromosomal translocated called Philadelphia chromosome -adults 40-60 account for 15-25% of all adult leukemias -most commonly associated with philadelphia chromosome (t[9;22]) which is present in 95% of cases- demonstration of its presence is diagnostic -present with increased neutrophils and metamyelocytes (kidney-shaped), splenomegaly -may accelerate to AML ('blast crisis') -very low leukocyte alkaline phosphatase (vs. leukemoid reaction) -the only curative tx for CML is a bone marrow transplant-allogenic -tyrosine-kinase inhibitors (TKIs) which have led to dramatically improved long-term survival

normal volume, normocytic anemias

-acute bleeding -aplastic -hemolytic -low erythropoietin -malignancy -chronic disease

leukemia diagnosis

-based on blood and bone marrow studies Acute vs. chronic -acute leukemia is characterized by the rapid growth of immature blood cells -chronic leukemia is distinguished by the excessive build up of relatively mature, but still abnormal blood cells Lymphoid vs. myeloid -it is called lymphocytic anemia when leukemia affects lymphoid cells (lymphocytes and plasma cells) -it is called myelogenous leukemia when myeloid cells (eosinophils, neutrophils, and basophils) are affected TX: -chem and/or radiation -sometimes bone marrow or stem cell transplant -CNS irradiation for "hidden cells"

Multiple myeloma

-cancer of plasma cells -abnormal response of plasma cells to antigens -MGUS and progression to MM -abnormal immunoglobulins -common chromosomal abnormalities -effect on osteoblasts and osteoclasts -plasma cell interactions with stromal bone marrow cells -most common bone cancer Pathophys: consequence of producing lots of monoclonal IG: -hyperviscocity (headache, visual changes, retinopathy) -kidney damage- from light chains only -bone pain-hypercalcemia and pathologic fractures from bone lesions -anemia/pancytopenia from bone marrow invasion -increased susceptibility to infection (PNA, UTI) Evaluation: -1 degree amyloidosis and punched-out lytic bone lesions on xray -characterized by monoclonal immunoglobulin on serum protein electrophoresis and Ig light changes in urine (bence-jones protein) -blood smear shows RBCs stacked like poker chips (rouleau formation) TX: -chemotherapy and bone marrow transplant Prognosis: poor, 5 year survival rate 35% plasma cells have fried egg appearance- lytic bone lesions clinical SX: -CRAB-hyperCalcemia, renal failure, anemia, bone lesions DX: -routine blood tests and imaging studies TX: -chemo -3 years median survival time

Vitamin B12 deficiency

-causes megaloblatic anemia -b12 needed for DNA synthesis -b12 only found in foods of animal origin

how is blood loss decreased during hemostasis?

-endothelin and vasoconstriction -platelet adhesion and vWF -release of serotonin, ADP, fibrinogen, calcium, thromboxane A2

neutrophils

-first responded to infection or inflammation -neutrophilia and granulocytosis -types of infection -leukemoid reaction -neutropenia and decreased ability to fight infections -clinical manifestations: sx of bacterial/fungal infections, respiratory tract most common site of infection -DX: serum neutrophil levels, cause of neutropenia/neutriphilia -TX: dependent on dx

Hb electrophoresis

-gold standard for evaluating patients with suspected hemoglobulinpathy- an abnormality in globin chain structure or globin chain synthesis -e.g. sickle cell disease or thalassemia

iron deficiency anemia

-microcytic, hypochromic RBCs -most common type of anemia and the most common cause of microcytic anemia Most widespread in: -women of childbearing age -children under 2 -elderly individuals Inadequate iron supply for hemoglobin production -chronic blood loss (e.g. menstruation or GI bleed- most common) -iron intake -problems with iron absorption SX: -pallor, fatigue, dyspnea on exert, brittle nails -pica -koilonychia Lab findings: -poikilocytosis (irregular shaped RBCs) -anisocytosis (irregular size) -decreased serum iron and increased TIBC -decreased hemoglobin and RBC count DX: -based on sx and hx -decreased serum ferritin -increased serum transferrin/TIBC -peripheral blood smear-microcytic anemia TX: -supplement iron (iron sulfate)

folate deficiency

-min daily requirement 50ug -usual dietary folate 50-500 ug -absorption in small intestine causes: -dietary causes 90%- alcohol abuse (not beer), pregnancy (increased demand) -malabsorption (celiac) -drug-induced (chemo like methotrexate) -exposure to UV light, including use of tanning beds DX: -megaloblasts -decreased folic acid level in blood TX: -folic acid can be taken as one tablet/day

acute lymphocytic leukemia

-most common cancer/death from cancer among US children -2500 new cases/yr in US -lymphoblast found in blood and bone marrow Sx: -tired -pallor -fever -easy bleeding or bruising -enlarged lymph nodes -bone pain Dx: -medical hx, PE -CBC & blood smears -bone marrow bx provides conclusive proof for ALL Tx: -chemo/radiation -immunotherapy (CAR T cell) prognosis: -most responsive to therapy -with aggressive chemo about 95% children obtain complete remission, 75-85% cured -only 35-40% of adults are cured -survival for children increased since 1960's

acute myelogenous leukemia

-most common in adults, med age 60 yo -20,800 cases new cases in 2015 -affects myeloid stem cells- give rise to granulocytes, monocytes, erythrocytes, and platelets -most patients have no clear-cut triggering event risk factors: -chemicals- benzene, smoking, chemo -radiation- high levels of x ray, radiation therapy -other blood disorders- Fanconti's anemia, MDS -genetics-down syndrome SX: -pallor (from anemia) -bleeding (thrombocytopenia) -frequent minor infection -mild fever -enlarged spleen and liver DX: -blood and bone marrow tests (requires that >20% of bone marrow cells must be myeloblasts) -myeloblasts with Auer rods- primarily seen in acute promyelocytic leukemia (M3) -M1-M6 TX: -chemo induces remission in a majority of patients, but only about 25% remain disease free for 5 year -tx of AML M3 can release Auer rods into circulation, causing DIC

chronic lymphocytic leukemia

-neoplasm of mature B cells -most common leukemia in adults -older adults (>60 yo, median age 70) SX: -indolent course -early-no typical sx -later- painless lymph node swelling, malaise, fever, night sweats, weight loss, hepatosplenomegaly and anemia DX: -lymphocytosis -increased smudge cells in peripheral blood smear* -bone marrow bx -warm antibody autoimmune hemolytic anemia is commonly seen in CLL patients TX: -probably "incurable" but a large group of CLL patients do not require therapy -symptomatic and supportive therapy -chemo/radiation -biological therapy -bone marrow transplant 5 year survival rate is 85%

anemia of chronic disease/inflammation

-normocytic -a mild to moderate anemia that is associated with inflammatory disorders, infection, and malignancy -second most common anemia -decreased RBC production by bone marrow, shortening of RBC survival Pathogenesis: -chronic inflammation-> increased IL 6 -> increased liver hepcidin -> binds to ferroportin (iron exporter) on macrophages and enterocytes -> decreased iron into plasma -> decreased RBC-> anemia of chronic disease SX; -underlying disease as cause for manifestations DX: -hx, pe -low reticulocyte count -low transferrin saturation -mild/moderate anemia -elevated inflammatory markers TX: -resolving underlying disorder and anemia

aplastic anemia

-normocytic -caused by primary bone marrow failure -failure of all marrow elements (RBCs, WBCs, megakaryocytes) -rare but serious -failure of bone marrow to produce multipotent HSC precursors -leads to pancytopenia (RBC, WBC, and platelets) Causes: -cause unclear in 50% -autoimmunity, drugs, chemicals are usually responsible SX: -sx of general anemia, leukocytopenia (infection) and thrombocytopenia (bleeding)

large-cell lymphoma

-originate in mature t cells -anaplastic or mature b cell for diffuse large b cell lymphoma -older children and teens -anaplastic 10%-med age 12 -diffuse b cell- 15% Clinical sx: -mass anywhere in body -diffuse large b cell: mediastinal mass or neck/abd lymph noes -anaplastic- painless lymphadenopathy, fever, malaise -not as aggressive as other lymphomas with rare metastasis to brain

Burkitt lymphoma

-originates from B lymphocytes -most linked to EBV -more common in males -ages 5-10 years-peak 4-6 years Clinical sx: -abd mass -pain -n/v -change in in bowel patterns -rapid growing head and neck lymphadenopathy -one of the most aggressive fast-growing cancers -cases in African account for almost all NHL -over 50% of childhood cancers develop in the jaw or other facial bones

high volume, macrocytic anemias

-pernicious -low folate

what does blood consist of?

-plasma -platelets -blood cells -life fluid of human body -essential for health and homeostasis -about 5l in the body -viscous fluid and connective tissue`

hemostasis

-process by which bleeding is stopped -primary and secondary -decreasing blood loss

Hodgkin's lymphoma

-typically starts in lymph nodes of upper body and spreads to other lymph nodes Types: -classical hodgkin's lymphoma -nodular lymphocyte predominance hodgkin's lymphoma *reed sternberg cells Clinical manifestations: -painless, enlarged lymph node in neck and/or supraclavicular area -mediastinal mass on cxr -b sx (fever, night sweats, weight loss >10%) Diagnosis: -biopsy of affected lymph node -staging system TX: -chemo -radiation -bone marrow or stem cell transplant

folic acid

-water soluble b vitamin -must be replenished through diet -deficiencies can occur quickly -factors leading to inadequate dietary intake

manifestations of leukemias

1. acute leukemia (three months onset) -anemia-fatigue, pallor -thrombocytopenia-> bleeding (nosebleeds, easy bruising, excessive/prolonged bleeding) -abnormal WBC count (e.g. neutropenia)-> infections -bone marrow involvement may cause bone tenderness and pain -CNS sx (leukemic cells cross blood-brain barrier)-headache, N/V, nerve palsies, sometimes convulsions and coma -weight loss -leukostasis -hyperuricemia

complications of sickle cell disease

1. aseptic necrosis femoral head 2. pigmented gallstone (prolonged hemolysis may lead to excessive bilirubin production) 3. autosplenectomy (damages spleen) 4. osteomyelitis (salmonella- but staffylococcus still most common 5. increased susceptibility to encapsulated organism infections (e.g. strep, salmonella 6. micro-hematuria 7. stroke DX: -hemoglobin electrophoresis TX: -stem cell transplants -meds -Hb F or blood transfusions

clinical sx of sickle cell disease

1. chronic hemolytic anemia 2. vaso-occlusive disease- sickled cells block microvasculature -infarcts with painful swelling of hands/feet -infarctions cause chronic damage to liver, spleen, heart, kidneys, bones -pulmonary infection-> acute chest syndrome -cerebral infarction-> stroke

what factors induce sickling in sickle cell disease?

1. concentration of HB S in RBC- > 60% 2. decreased pH-> decreased O2 affinity and make sx worse 3. preceded by infection 25% of the time -human parvovirus B19 in common viral cause 4. cold weather due to reflex vasospasm 5. dehydration in warm weather

types of sickle cell disease

1. sickle cell trait (A/S) -no anemia -hemoglobin S (Hb S) represents 25-40% of their Hb -under normal circumstances, RBCs do not hemolyze 2. sickle cell anemia (S/S) -initially infants RBCs mainly contain fetal Hb F -infants are clinically unaffected until 4-6 months of age when Hb F production is largely replaced by HB S production

blood components

45% formed elements like platelets, rbcs, and wbcs (95% RBCs) 55% plasma -92% water -7% proteins

A mother brings in her 7-year-old son for an evaluation. The mother states her son has not been eating well. When questioned, the boy states he is not eating because he feels ÒbumpsÓ in his neck and like his face is getting big. The mother notes that his face looks different. The family just moved from Africa. The vital signs are normal and his height and weight are appropriate for his age. Physical exam findings are unremarkable except for enlarged tonsils and asymmetrical facial bone distortion and nontender, enlarged lymph nodes palpated in his head and neck region. Based on these findings, which type of childhood lymphoma is the most likely diagnosis? A. Burkitt lymphoma B. large-cell lymphoma C. lymphoblastic lymphoma D. hodgkin lymphoma

A. Burkitt lymphoma

Von Willebrand disease is caused by which of the following? A. deficiency of factor VIII and poor platelet function B. lack of factor IX and poor platelet function C. deficiency of clotting factors VIII and IX

A. deficiency of factor VII and poor platelet function -these two conditions come together to cause the disseminated bleeding

Parents just learned that their newborn son has sickle cell anemia based on newborn screening. They want to know what kind of sx he might get from the disease. What should the parents be told? A. your baby's hands and feet may swell B. sx at first usually consist of back pain C. your baby may become insensitive to pain D. your baby may develop a heart murmur

A. hands and feet may swell

Most lymphomas arise in: A. Reed-sternberg cells B. B cells C. T cells D. NK cells

B. b cells

A 66-year-old black man comes in complaining of back pain. Diagnostic tests are done and include an X-ray, a complete blood count with differential, and a comprehensive metabolic panel (e.g., glucose, potassium, calcium, albumin). Which findings are consistent with multiple myeloma? A. hypocalcemia B. diffuse well-defined "punched out" lytic lesions C. high platelet level D. high neutrophil count

B. diffuse well-defined punched out lytic lesions -HYPERcalcemia -low platelet and neutrophil counts

All of the following are cellular components of blood except? A. macrophages B. eosinophils C. mast cells D. neutrophils

C. Mast cells mast cells are not blood cells; rather they are found in connective tissue and initiate the inflammatory response

The suffix -penia refers to a ____in number A. stasis B. increase C. decrease

C. decrease

In hodgkin lymphoma, B cells can become defective as a result of: A. premature apoptosis due to lack of differentiation B. t-cell inactivation of B cells C. errors in immunoglobulin gene arrangements D. enhanced conversion into plasma B memory cells

C. errors in immunoglobulin arrangements

Which of the following disease etiologies may be directly related to dietary insufficiency? A. erythroblastosis fetalis B. polycythemia vera C. iron deficiency anemia D. sickle cell anemia

C. iron deficiency anemia

Which of the following is a characteristic of non-hodgkin lymphoma in comparison to hodgkin lymphoma? A. it accounts for only 10% of all lymphomas B. Reed-sternberg cells are generally present C. multiple lymph nodes are usually involved D. incidence is higher in young adults

C. multiple lymph nodes usually involved -NHL accounts for 90% of lymphomas -reed sternberg cells not present -incidence higher in adults

Von Willebrand factor is directly involved in: A. formation of fibrin clot B. clot dissolution C. platelet adhesion and aggregation D. platelet production

C. platelet adhesion and aggregation

Which of the following is a common feature of all forms of leukemia? A. proliferation of malignant lymphocytes altering leukocyte production B. reduction in leukocytes leading to bone marrow destruction C. uncontrolled proliferation of malignant leukocytes causing overcrowding of bone marrow and abnormal hematopoiesis D. tumor cell masses in the bone marrow that usually result in bone destruction

C. uncontrolled proliferation of malignant leukocytes causing overcrowding of bone marrow and abnormal hematopoiesis

Thrombotic Thrombocytopenic Purpura (TTP)

Coagulation disorder •Deficiency of enzyme necessary for cleaving von Willebrand factor (vWF) Increased clotting and decreased availability of platelets Characterized by microthrombi in microvasculature, thrombocytopenia, bleeding Hereditary mutations of ADAMTS13 Acquired TTP Clinical manifestations •Acute or insidious, involving multiple systems •Neurologic, cardiovascular, and gastrointestinal manifestations Diagnosis •High LDH and reticulocyte levels Treatment •Plasmapheresis

DIC is associated with which of the following? A. release of tissue factor B. endothelial damage C. activation of factor X D. all of the above

D. all are correct

____ are two important cofactors necessary in the coagulation cascade? A. fibrin and thrombin B. fibrinogen and vWF C. thromboxane A2 and calcium D. calcium and fibrinogen

D. calcium and fibrinogen

A 55 yo woman has a hypochromic, microcytic anemia. The most likely cause is: A. replacement of bone marrow by metastatic tumor B. vit b12 or folic acid deficiency C. hemolysis of RBCs due to antibodies D. iron deficiency resulting from chronic GI blood loss

D. iron deficiency

Bilirubin is an important indicator of which of the following: A. rate of hemoglobin production B. rate of RBC production C. rate of hemoglobin oxidation D. rate of RBC breakdown

D. rate of RBC breakdown -bilirubin is a product of RBC breakdown and will be elevated if breakdown is accelerated (hemolytic anemia)

is the following statement true or false? Hematopoietic growth factors are only associated with normal production of cells?

False In disease states like polycythemia vera, leukemia, and other blood cancers, inappropriate production of growth factors does occur

T/F: Manifestations of Anemia are dependent upon the causative factor in the initiation of the disease?

False-regardless of the causation, the main detrimental effect is systemic hypoxia

Alpha Thalassemia

Genetics -There are four genes for α globin ( two are maternal in origin and two are paternal in origin) -a-Thalassemia is due to gene deletion (HBA1 and HBA2) Clinical disease states •Normal: four a genes (aa/aa) and 100% a chains •Silent carrier: one gene deletion (-a/aa), 75% a chains. -asymptomatic and all lab tests are normal • a-Thalassemia trait: two gene deletions, 50% a chains. -Genotype: cis (--/aa) is seen in Asians -Genotype: trans (-a/-a) is seen in African-Americans •Hb H disease: three deletions (--/-a), 25% a chains. -↑ Hb H (b4) forms Heinz body. •Hydrops fetalis: four gene deletions (--/--), 0% a chains. -↑ Hb Barts (g4) Results intrauterine fetal death

Beta Thalassemia

Genetics •There are two b-globin chain genes •Mainly duo to point mutations, which are form either some b chains (b+) or none b chain (b0) b -Thalassemia minor or Trait (heterozygous): •Asymptomatic or minimal hypochromic microcytic anemia •Usually raised Hb A2 (a2d2) on Hb electrophoresis •Peripheral Blood: Target cells, polychromatophilia, basophilic stippling, occasional nucleated RBC, anisocytosis, poikilocytosis

hemophilia

Hemophilia A •Deficiency or abnormality of clotting factor VIII Hemophilia B •Abnormality of clotting factor IX Clinical manifestations •Bleeding, petechiae, bruising, gastrointestinal bleeding, hematuria Diagnosis •Examination of bleeding studies Treatment •Replacement of clotting factors •Bleeding precautions

Hodgkin vs Non-Hodgkin Lymphoma

Hodgkin: -more often localized to a single axial group of nodes (cervical, mediastinal, para-aortic) -orderly spread by contiguity -mesenteric nodes and Waldeyer ring rarely involved -extranodal presentation rare Non-Hodgkin -more frequent involvement of multiple peripheral nodes -noncontiguous spread -Waldeyer ring and mesenteric nodes commonly involved -extranodal presentation common

Immune Thrombocytopenic Purpura (ITP)

Hypocoagulopathy state •Immune system destroying its own platelets Secondary ITP causes •Autoimmune diseases, immunizations from live vaccine, infections, cancer Autoantibody mediated development Primary ITP •Most common cause •Acute or chronic Clinical manifestations •Often asymptomatic •Abnormal bleeding Diagnosis •Usually by exclusion Management •Goal to increase platelet count -Prevent or manage severe bleeding

thrombocythemia

Increase in platelet count Secondary thrombocytosis •Pooling of platelets in circulation: -After splenectomy -Reactive response to infections or inflammations Primary thrombocytosis •Myeloproliferative neoplasm

Disseminated Intravascular Coagulation (DIC)

Life-threatening disorder •Complication of other diseases and conditions Abnormally active coagulation and fibrinolysis Causes: endotoxic shock, meningococcemia, amniotic fluid embolism Global intravascular consumption of platelets, clotting factors and fibrin Disorders associated with DIC Multisystem manifestations Lab: ↑ PT, ↑ PTT, ↑ BT, D-dimer (best test for DIC), thrombocytopenia, schistocytes Diagnosis through CBC and coagulation studies Complicated management balancing clot prevention and bleeding treatment Rx: treat underlying disease causing DIC, low dose heparin (block thrombin, hence preventing clots and consumption of coagulation factors

thrombocytopenia

Low platelet levels •High risk for life-threatening bleeding •Below 15,000 cells/mL3 results in spontaneous bleeding -Petechiae and ecchymoses Decreased production or increased destruction of platelets •Medication history •Primary immune thrombocytopenia

non-hodgkin's lymphoma

Prevalence -90% of all lymphomas -5% of childhood cancers Categories and subtypes: -Burkitt lymphoma -lymphoblastic lymphoma -large cell lymphoma clinical manifestations: -aggressive and indolent types -unorganized metastasis DX: -testing and staging similar to HL TX: -dependent on subtype -worse prognosis than HL*

iron overload

Results from increased intake or absorption •Therapies and disorders -Four types of hereditary hemochromatosis Excess iron •Saturation of transferrin •Iron binding to other proteins -Absorbed by cells that transform iron into reactive oxygen species Clinical manifestations •Nonspecific and develop slowly •Evident once there is organ damage Diagnosis •High iron, ferritin, and transferrin saturation levels •Low iron binding capacity •Iron deposition visualized by MRI Treatment to prevent organ damage •Phlebotomy and chelation therapy

sickle cell disease

a disorder of chronic hemolytic anemia and microvascular occlusion involving the Hb S mutation in the B-globin gene on chromosome 1 -one of the most common inherited blood disorders in the US -1/500 African-descent births -have resistance to Plasmodium falciparum- infection (malaria) Pathophys: -normal hemoglobin 1 (a2b2) replaced with hemoglobin s (a2b2s) path: -normal hemoglobin A (a2b2) replaced by hemoglobin a2b2s -substitution of valine (GTG) for gluamic acid (GAG) -occurs in the 6th position of the B-chain

sx of sickle cell anemia

abd pain, GU dysfunction, ophthalmic complications- vitreous hemorrhage, retinal detachment and blindness -cardiomegaly and systolic flow murmurs -splenic sequestration crisis is caused by pooled blood, which enlarges spleen -dilute urine Vaso-occlusive crisis: -CVA caused by occlusion of vessels in brain -chest syndrome- CP, fever, cough and can be precipitated by or result from PNA -painful episode is the most frequent complication occurring in joints and limbs -hand-and-foot syndrome may be the first of vaso-occlusion

polycythemia

aka erythrocytosis an increase in the concentration of RBCs and Hb in the blood, can result from either an absolute increase in body red cell mass (absolute polycythemia) or from a decrease in plasma volume (relative polycythemia). Types: •Primary polycythemia (polycythemia vera): either congenital or acquired. -Bone marrow produces too many blood cells, -↓ erythropoeitin -Caused by mutation in the JAK2 gene •Secondary polycythemia (a consequence of increased erythropoietin) -Chronic hypoxia, caused by cardiac or pulmonary disease or residence at high altitude, adult polycystic kidney disease (APKD) or renal cell carcinoma. -↑ erythropoeitin •Relative polycythemia (a decrease in the volume of plasma) Clinical manifestations: •Visual disturbances, hypertension, and splenomegaly •Pruritus after contact with warm water •Vasomotor and microvascular thrombotic changes Diagnosis •Low serum erythropoietin (primary) and peripheral blood mutation of JAK2 Treatment •Chemotherapy/cytoreductive agents -Myelosuppressive medications such as hydroxyurea •Emergency treatment - phlebotomy (removal of blood from the circulation)

anemia

an abnormally low hemoglobin concentration in the blood -common acquired or inherited disorder -impairs oxygen-carrying capacity of the blood -decreased RBC production or increased RBC loss -classified by cause of anemia or RBC morphology -manifests as weakness, pallor, fatigue, syncope, dyspnea, and tachycardia

sickle cell crisis

an acute worsening of the patient's baseline anemia -pallor -tachycardia -fatigue -the shortened rbc life of sickle cell patients results in abrupt, life-threatening situations -the crisis triggered by Parvovirus b19 -profound anemia -decreased reticulocyte count (<1%)

Von Willebrand disease

an autosomal dominant disorder marked by def. of von Willebrand's factor (vWF), which serves as a carrier protein for factor VIII synthesized by endothelial cells. Most common hereditary bleeding disorder (1% of the population and affects men and women equally). Three types of hereditary VWD are VWD type 1 (AD), VWD type 2 (AD), and VWD type 3 (AR), and acquired type (patients with autoantibodies). VWD type 1 is the most common type (60-80% of all VWD cases). Manifests as abnormal bleeding from nose, mouth and other mucous membrane. Lab: ↑ bleeding time (BT), ↑ PTT, normal PT Treatment: Bleeding control measures, Cryoprecipitate infusions or DDAVP (desmopressin), which promotes the release of von Willebrand factor and factor VIII

Beta thalassemia major

b -Thalassemia major or Cooley's anemia (homozygous) •Pts are normal at birth. Symptoms develop at 6~9 months because Hb F (a2g2) level decline. •Severe hemolytic anemia, results from ↓ RBC lifespan Clinical: •hypochromic microcytic anemia, splenomegaly, jaundice, "crew-cut" skull X-ray, •↑ Hb F (90%), ↑ Hb A2 (a2d2), ↓ Hb A., ↑ reticulocytes, target cell.

Thalassemia treatment

blood transfusion, chelation therapy, bone marrow transplant, splenectomy

pernicous anemia

caused by chronic gastritis, which is associated with failure of production of intrinsic factor by the parietal cells of the stomach, essential for vit b12 absorption in the small intestine lab findings: -RBCs large, often oval shape -poikilocytosis and teardrop shapes -anti-intrinsic factor antibodies (specific but not sensitive) -anti-parietal cell antibodies (sensitive but not specific) -schilling test (patient is given radiolabeled vit b12 to drink) DX: -sx and lab findings -macrocytic -autoantibodies TX -oral or IM injection of b12

eosinophils

control and augment inflammatory response -high with parasitic infections

leukocytes

diverse group of cells -trigger inflammatory process and combat infections -diseases originate from deficiencies of leukocytes

hyperuricemia

elevated uric acid in the blood that result from increased proliferation and metabolic alterations of leukemic cells-> stone formation or gout

transferrin

glycoprotein, which binds iron tightly but not reversibly

what is the function of blood?

provides nutrients and oxygen to tissues -aids in excretion of waste products

reticulocyte count

immature red blood cell -normal 0.5-1.5% Correct reticulocyte count = patient hematocrit/45 x reticulocyte count -< 2% poor bone marrow response (ineffective) - > 3% good bone marrow response (effective erythropoietin)

lymphocytes and monocytes

key cells involved in immune response -increased with viral infections -lymphocytosis -lymphocytopenia -monocyte alterations

thalassemia

microcytic, hypochromic -genetic disorders characterized by deficient production of either of the two globin chains of hemoglobin -thalassemia provides a protective advantage to carriers, such as against malaria Types: 1. alpha thalassemia- has decreased alpha-globin chains with relative excess beta-chains -southeast asian (incidence common) -black patients -not as common -mutations in HBA1 and HBA2 genes on chromosome 16 2. beta-thalassemia- has decreased beta-globin chains with relative excess alpha chains -southern Italy and Mediterranean islands -central Africa -asia -mutation in HBB gene on chromosome 11 -categorized by severity of sx

total iron binding capacity

normal 240-450 mg/dl -approximates serum transferrin -plasma protein for iron deficiency- will be raised with iron deficiency -low in infections, inflammation, and malignant disease

serum iron

normal 60-170 mg/dl -serum iron measures the amount of circulating iron that is bound to transferrin -reduced in iron deficiency anemia -reduced in infections, inflammations, and malignant disease

aplastic anemia

normocytic DX: -CBC -bone marrow bx TX: -underlying causes -measures for tx of complications: o2 therapy, infection control and tx, bleeding precautions

lymphoid system

organs connecting hematologic and immune systems -thymus as site of T cell maturation -bone marrow as site of hematopoiesis -spleen as blood filter -lymph nodes to protect against infection

lymphoblastic lymphoma

originate in precursor B or T lymphocytes (T more common) -males 2x more likely -median dx 12 clinical sx: T cell- thymus- retrosternal or anterior tracheal mass with difficulty breathing, CP, susceptibility to infections B cell-bone marrow- painless lymphadenopathy in neck both have b sx -aggressive, fast growing ->25% bone marrow lymphoblast categorized as acute lymphocytic anemia

transferrin saturation

percentage = serum iron level x 100% / TIBC- normal 20-50%

Hematopoiesis

process of blood formation -occurs in bone marrow -requires supply of hematopoietic stem cells (multipotent cells) -hepcidin's regulatory role for iron uptake and transport -hemoglobin