HEMATOLOGY; ALTERATIONS OF BLOOD CELL AND LYMPHOID FUNCTION

Blood Plasma –Complex, aqueous –Organic, inorganic molecules Plasma proteins –Greatest weight in total plasma –Important plasma proteins: Albumins Globulins Clotting factors

Blood – cont’d Other components –Formed elements (blood cells) Erythrocytes (= red blood cells = rbc’s) Leukocytes (= white blood cells = wbc’s) Lymphocytes (= B and T cells) Thrombocytes (= platelets) Development (= hematopoiesis) –Common stem cell Mitosis signaled by biochem’s released from the body Differentiate  needed blood cell Hematopoiesis/cell breakdown continuous

Erythrocytes (= Red Blood Cells = RBC’s) Development = erythropoiesis –Erythropoietin Renal hormone Rel’d when kidney senses decr’d blood oxygen  red bone marrow Signals differentiation of common stem cell  rbc’s

RBC’s – cont’d Rbc cytoplasm contains –Hemoglobin –Other proteins, electrolytes –Not many (if any) organelles No nucleus Doesn’t replicate on own in bloodstream –Where do more rbc’s come from?

RBC’s – cont’d Hemoglobin (Hb) – carries O 2 and CO 2 within rbc’s –Composition Four protein chains (= globin) Complex organic molecule embedded in each globin chain (= heme) Iron (Fe) atom held in globin –“Binds” oxygen –Body’s synth of Hb requires Sufficient Fe and amino acids Vitamins folate (or folic acid) and B12

RBC’s – cont’d Hb – cont’d –Rbc/Hb breakdown Healthy rbc’s live 120 days –Approx. 174 million rbc’s break down per minute –In liver and spleen Hb released, broken down following rbc breakdown –Globin  amino acids; recycled  new proteins –Fe – stored or recycled –Heme converted  bilirubin »Bilirubin either stored or recycled, or »Further converted in liver to bile

Abnormalities of RBC’s Anemias –  Clinical symptoms: Fatigue Dyspnea Syncope Angina Tachycardia Organ dysfunctions

Anemias – cont’d Macrocytic/megaloblastic – large rbc’s –Commonly due to deficiency of Vit B12 or folate –Pernicious anemia - typical Possible causes –Congenital –deficiency in protein nec to absorb B12 from small intestine –Adult onset – one example: autoimmune dysfunction  destruction of gastric mucosa Develops slowly Fatal if untreated

Anemias – cont’d Microcytic –abnormally small rbc’s w/ decr’d Hb –Possible causes: disorders of Fe metabolism Globin synthesis Heme synthesis

Anemias – cont’d Microcytic – cont’d –Iron deficiency anemia – typical Common causes –Insufficient Fe intake –Chronic blood loss (even 2-4 mL/day) »Men – gastrointestinal bleeding »Women – profuse menstruation, pregnancy Other causes –Drugs  gastrointestinal bleeding –Eating disorders  insufficient Fe

Anemias – cont’d Microcytic – cont’d –Treatment Eliminate blood loss Replace Fe Normocytic –Aplastic anemia - typical Bone marrow dysfunction  underdeveloped, defective, absent marrow or stem cells

Anemias – cont’d Normocytic – cont’d –Aplastic anemia – cont’d Possible causes of bone marrow dysfunction: –Cancer cells in marrow –Autoimmune response –Renal failure –Exposure to radiation, drugs, toxins harming bone marrow Clinical symptoms – those typical of anemias Treatment –Treat underlying disorder –Blood transfusions to increase [Hb] –Bone marrow transplant

Abnormalities of RBC’s – cont’d Myeloproliferative disorders –Polycythemia = excessive proliferation of rbc’s Secondary is most common –Physiological response to hypoxia –Seen in »Smokers »Those w/ congestive heart failure »Those w/ cardiopulmonary diseases

Polycythemia – cont’d Leads to –Incr’d blood volume, viscosity –Congestion of liver, spleen –Clotting; thrombus formation Clinical –Headache, dizziness, weakness –Increased blood pressure –Itching/sweating Treatment –Reduce blood volume (= phlebotomy) to reduce rbc # –Control symptoms –Prevent thrombosis

Sickle Cell RBC’s

Leukocytes (= White Blood Cells = wbc’s) Granulocytes – granules in cytoplasm –Granules contain Enzymes to kill invading cells, break down cell debris Other biochem’s that signal, mediate inflammatory response –Cell types (mostly phagocytic) Neutrophils Eosinophils Basophils

Leukocytes (= White Blood Cells = wbc’s) Agranulocytes – no granules in cytoplasm –Also impt phagocytes, release biochem signals –Cell types Monocytes Macrophages

Leukocytes (= White Blood Cells = wbc’s) Origination –Same red bone marrow stem cells as rbc’s (and platelets and lymphocytes) –Granulocytes mature in marrow Lifetime hours to days –Agranulocytes mature in blood Live about 2-3 months

Leukocytes (= White Blood Cells = wbc’s) Production incr’s when –Infection –Presence of steroids –Decr’d reserve leukocyte pool in bone marrow

Leukocytes (= White Blood Cells = wbc’s) Abnormalities –Leukocytosis = incr’d # wbc’s May be a normal response –When?? OR may signify a disease state –When?? –Leukopenia = decr’d # wbc’s Always pathological

Leukemias -- malignant disorders of blood cells Single cell may undergo transformation to dysfunctional cell, then proliferates to dysfunctional clones –Not nec faster prolif’n, but do displace normal cells Result: dysfunct’l cells accumulate, compete w/ proliferation of normal blood cells within bone marrow –  Overcrowding of bone marrow  decr’d production of normal, functioning blood cells

Leukemias -- cont’d Probably risk env. factors + genetic predisposition –Risk factors Some disorders of bone marrow, other organs; can progress to acute leukemias Some viruses Ionizing radiation in large doses Drugs Genetic - sibling occurrence

Leukemias -- cont’d Classified as acute/chronic; myeloid/lymphoid –Acute leukemias Characteristics –Abrupt onset –Rapid progression –Severe symptoms –Histology: incr’d # immature blood cells Survival rate

Leukemias -- cont’d –Acute leukemias – cont’d Clinical –Signs/symptoms related to bone marrow depression »Fatigue »Bleeding »Fever »Anorexia/weight loss »Enlargement of liver/spleen

Leukemias -- cont’d –Acute leukemias – cont’d Clinical – cont’d »Neurologic effects (headache, vomiting, facial palsy, blurred vision Early detection difficult Treatment –Chemotherapy –Immunotherapy –Marrow transplants

Leukemias -- cont’d –Chronic leukemias Characteristics –Predominant cell mature but abnormal function –Gradual onset –Relatively longer survival time Chronic lymphocytic one example –B cells fail to mature to active plasma cells –Ig’s not produced, plasma cell # decr’d –Most signification »Incr’d infections »Incr’d autoimmune response

Chronic lymphocytic leukemia (CLL) Lymphocyte (small, mature-looking) Acute lymphocytic leukemia (ALL) Two lymphoblasts, one neutrophil

Lymphomas Often in secondary lymph tissue –Lymph nodes, spleen, tonsils, intestinal lymphatic tissue –Not in blood-borne cells, so “solid tumor” Hodgkin’s - distinctive abnormal chromosomes –Cause unknown. May be Genetic Transmissible agent Other (strange) risk factors include: tonsillectomy/appendectomy; wood working (?)

Lymphomas – cont’d Hodgkin’s – cont’d –Clinical Painless swelling or lump in neck Intermittent fever Weakness, weight loss Obstruction/pressure can lead to secondary involvement of –Lung –Spinal cord/neurons –Skin

Lymphomas – cont’d Hodgkin’s – cont’d –Early detection difficult –Treatment Chemotherapy Radiation Prognosis good with early treatment

Lymphomas – cont’d Non-Hodgkin’s –Cause unknown –See B-cell and T-cell abnormalities –Clinical Lymph node enlargement (gradual, painless) Extra-nodal areas can be affected –Treatment Bone marrow transplant Prognosis good if growth is restricted to lymph node

Thrombocytes = Platelets Characteristics –Prod’d by fragmentation of megakaryocyte –Life span ~ 3 days –Many held in spleen Coagulation (= hemostasis): Converts fluid blood to a nonflowing gel –Long protein threads (fibrin) formed, come together to form blood clot

Thrombocytes – cont’d Coagulation – cont’d –Many proteins/enzymes/factors nec for clotting “cascade” –Platelets bind at site of clot then activated  Nec biochem changes at clot site  successful clot formed Disorders of platelets –Thrombocytopenia Decr’d # platelets, due to Decr’d prod’n platelets, seen w/ –Tumors –Drugs/toxins –Other

Thrombocytes – cont’d –Thrombocytopenia causes – cont’d OR incr’d clearance of platelets, seen with –Splenomegaly –Tumors –Infections –Immune disorders –Clotting factor disorders Clotting factors can’t work to make a successful clot May be –Genetic »Hemophilia »VonWillebrand’s disease

Thrombocytes – cont’d –Clotting factor disorders – cont’d May be –Acquired »Liver disease (where some clotting factors prod’d) –Drugs/toxins –Inappropriate clotting Body has anticlotting mechanism (also necessary) –Keeps clots from being too large, blocking vessel –Keeps unneeded clots from forming –Important in vascular disorders