HEMATOLOGY; ALTERATIONS OF BLOOD CELL AND LYMPHOID FUNCTION

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HEMATOLOGY ALTERATIONS OF BLOOD
CELL AND LYMPHOID FUNCTION
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Blood

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

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Blood contd

• Other components
• Formed elements (blood cells)
• Erythrocytes ( red blood cells rbcs)
• Leukocytes ( white blood cells wbcs)
• Lymphocytes ( B and T cells)
• Thrombocytes ( platelets)
• Development ( hematopoiesis)
• Common stem cell
• Mitosis signaled by biochems released from the
  body
• Differentiate ? needed blood cell
• Hematopoiesis/cell breakdown continuous

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Erythrocytes ( Red Blood Cells RBCs)

• Development erythropoiesis
• Erythropoietin
• Renal hormone
• Reld when kidney senses decrd blood oxygen
• ? red bone marrow
• Signals differentiation of common stem cell ?
  rbcs

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RBCs contd

• Rbc cytoplasm contains
• Hemoglobin
• Other proteins, electrolytes
• Not many (if any) organelles
• No nucleus
• Doesnt replicate on own in bloodstream
• Where do more rbcs come from?

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RBCs contd

• Hemoglobin (Hb) carries O2 and CO2 within rbcs
• Composition
• Four protein chains ( globin)
• Complex organic molecule embedded in each globin
  chain ( heme)
• Iron (Fe) atom held in globin
• Binds oxygen
• Bodys synth of Hb requires
• Sufficient Fe and amino acids
• Vitamins folate (or folic acid) and B12

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RBCs contd

• Hb contd
• Rbc/Hb breakdown
• Healthy rbcs live 120 days
• Approx. 174 million rbcs 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

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Abnormalities of RBCs

• Anemias
• ? Clinical symptoms
• Fatigue
• Dyspnea
• Syncope
• Angina
• Tachycardia
• Organ dysfunctions

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Anemias contd

• Macrocytic/megaloblastic large rbcs
• 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

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Anemias contd

• Microcytic abnormally small rbcs w/ decrd Hb
• Possible causes disorders of
• Fe metabolism
• Globin synthesis
• Heme synthesis

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Anemias contd

• Microcytic contd
• 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

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Anemias contd

• Microcytic contd
• Treatment
• Eliminate blood loss
• Replace Fe
• Normocytic
• Aplastic anemia - typical
• Bone marrow dysfunction ? underdeveloped,
  defective, absent marrow or stem cells

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Anemias contd

• Normocytic contd
• Aplastic anemia contd
• 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

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Abnormalities of RBCs contd

• Myeloproliferative disorders
• Polycythemia excessive proliferation of rbcs
• Secondary is most common
• Physiological response to hypoxia
• Seen in
• Smokers
• Those w/ congestive heart failure
• Those w/ cardiopulmonary diseases

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Polycythemia contd

• Leads to
• Incrd 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

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Sickle Cell RBCs
 
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Leukocytes ( White Blood Cells wbcs)

• Granulocytes granules in cytoplasm
• Granules contain
• Enzymes to kill invading cells, break down cell
  debris
• Other biochems that signal, mediate inflammatory
  response
• Cell types (mostly phagocytic)
• Neutrophils
• Eosinophils
• Basophils

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Leukocytes ( White Blood Cells wbcs)

• Agranulocytes no granules in cytoplasm
• Also impt phagocytes, release biochem signals
• Cell types
• Monocytes
• Macrophages

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Leukocytes ( White Blood Cells wbcs)

• Origination
• Same red bone marrow stem cells as rbcs (and
  platelets and lymphocytes)
• Granulocytes mature in marrow
• Lifetime hours to days
• Agranulocytes mature in blood
• Live about 2-3 months

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Leukocytes ( White Blood Cells wbcs)

• Production incrs when
• Infection
• Presence of steroids
• Decrd reserve leukocyte pool in bone marrow

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Leukocytes ( White Blood Cells wbcs)

• Abnormalities
• Leukocytosis incrd wbcs
• May be a normal response
• When??
• OR may signify a disease state
• When??
• Leukopenia decrd wbcs
• Always pathological

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Leukemias -- malignant disorders of blood
cells

• Single cell may undergo transformation to
  dysfunctional cell, then proliferates to
  dysfunctional clones
• Not nec faster prolifn, but do displace normal
  cells
• Result dysfunctl cells accumulate, compete w/
  proliferation of normal blood cells within bone
  marrow
• ? Overcrowding of bone marrow ? decrd production
  of normal, functioning blood cells

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Leukemias -- contd

• 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

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Leukemias -- contd

• Classified as acute/chronic myeloid/lymphoid
• Acute leukemias
• Characteristics
• Abrupt onset
• Rapid progression
• Severe symptoms
• Histology incrd immature blood cells
• Survival rate

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Leukemias -- contd

• Acute leukemias contd
• Clinical
• Signs/symptoms related to bone marrow depression
• Fatigue
• Bleeding
• Fever
• Anorexia/weight loss
• Enlargement of liver/spleen

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Leukemias -- contd

• Acute leukemias contd
• Clinical contd
• Neurologic effects (headache, vomiting, facial
  palsy, blurred vision
• Early detection difficult
• Treatment
• Chemotherapy
• Immunotherapy
• Marrow transplants

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Leukemias -- contd

• 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
• Igs not produced, plasma cell decrd
• Most signification
• Incrd infections
• Incrd autoimmune response

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Acute lymphocytic leukemia (ALL) Two
lymphoblasts, one neutrophil
 
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Lymphomas

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

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Lymphomas contd

• Hodgkins contd
• 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

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Lymphomas contd

• Hodgkins contd
• Early detection difficult
• Treatment
• Chemotherapy
• Radiation
• Prognosis good with early treatment

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Lymphomas contd

• Non-Hodgkins
• 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

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Thrombocytes Platelets

• Characteristics
• Prodd 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

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Thrombocytes contd

• Coagulation contd
• 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
• Decrd platelets, due to
• Decrd prodn platelets, seen w/
• Tumors
• Drugs/toxins
• Other

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Thrombocytes contd

• Thrombocytopenia causes contd
• OR incrd clearance of platelets, seen with
• Splenomegaly
• Tumors
• Infections
• Immune disorders
• Clotting factor disorders
• Clotting factors cant work to make a successful
  clot
• May be
• Genetic
• Hemophilia
• VonWillebrands disease

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Thrombocytes contd

• Clotting factor disorders contd
• May be
• Acquired
• Liver disease (where some clotting factors
  prodd)
• 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