Erythrocyte disorders fall into 2 groups:
1) Anemias (too little)
- Deficit of RBCs
2) Polycythemias (too much)
- Excess RBCs
Anemia:
Decreased oxygen carrying capacity of the blood
General effects of anemia are due to:
1) Tissue Hypoxia (decrease Oxygen carrying capacity of the blood)
2) Efforts to compensate for the low oxygen-carrying capacity
Tissue hypoxia leads to:
1) Fatigue
2) Weakness
3) Dyspnea
4) Pallor
5) Ischemic pain
6) Lethargy (pale)
7) Lightheadedness
6 and 7 are CNS
Efforts to compensate include:
1) Vasoconstriction: to increased MAP
2) Tachypnea: Increase ventilation
3) Tachycardia: Increase Cardiac Output
4) Increased 2,3-DPG (diphosphoglycerate) production
Anemia commonly result from:
1) Decrease RBC production
- Stem cell production (aplastic anemia)
- Erythropoietin deficit (renal disease)
- Nutritional deficiencies: iron, B12, folate
2) Increased RBC destruction or excessive loss
- Hemolysis (hemolytic anemia: ABO and Rh incompabili
Determination of the cause of anemia is based on:
1) Medical history
2) Differential signs and symptoms
3) Results of laboratory studies
Classify anemias:
1) "Cytic" refers to size
- Nomocytic
- Macrocytic (increased mean corpuscular volume) MCV
- Microcytic (decreased MCV)
2) "Chromic" refers to hemoglobin content
- Normochromic
- Hyperchromic (increased mean corpuscular hemoglobin concentration) MCHC
- Hy
Anaplastic anemia:
History of toxic or radiation injury to bone marrow
Accompanying leukopenia and thrombocytopenia
RBC are normocytic and nomorchormic
Anema of chronic renal failure:
History of renal disease
Decreased EPO and EPO responsiveness
RBCs are normocytic and normochromic
Anemia related to Vitamin B12 (Cobalamin):
History of poor intake or gastrointestinal disease
Shilling test is used to diagnose primary pernicious anemia
Accompanying paraesthesias of hands and feet.
RBCs are megablastic (macrocytic) and normochormic
Iron deficiency anemia
History of poor iron intake or chronic blood loss
Serum ferritin and irons levels are decreased
RBCs are microcytic and hypochromic
Hemolytic:
History of ABO and Rh incompability or drug exposure.
Exp: hemolytic disease of newborn, antibody-mediated drug reactions (Type II hypersensitivity reactions)
Increased bilirubin, jaundice, and a positive direct antiglobulin test (DAT) are observed.
RBCs
Acute blood loss
History of trauma, surgery, known bleeding
Volume depletion accompany with acute blood loss
RBCs are normal
Sickle cell anemia is:
Inherited, autosomal recessive disorder
- Homozygous HbS
- Trait is heterozygous HbS/HbA
HbS is formed by a genetic in which only 1 animo acid is replaced
HbS react to decreased O2 and dehydration by sickling
Normocytic, normochromic
Abnormalities of sickle cell anemia:
1) Hemoglobin structure
2) Cell shape
3) Membrane structure
4) Energy production
The major effects of sickle cell anemia are due to:
1) Hemolysis
2) Vaso occlusion
- When O2 level is low, RBCs sickle, becoming elongated and rigid.
- As blood circulates through the body, the oxygen levels may decrease. Erythocytes sickle and are unable to pass easily through small arteries (can't fold).
Manifestations of hemolysis are common and include:
1) Hyperbilirubinemia
3) Jaundice
General management of anemia includes:
1) Remove the cause if possible (MOST COMMON IS IRON)
2) Restore the Oxygen carrying capacity with blood transfusion when necessary
3) Prevent the complications of ischemia via: rest and oxygen therapy
4) Prevent the complication of hemolysis via: increas
Hemolytic disease of the newborn (erythroblastosis fetalis):
Type II Hypersensitivity:
- Fetal Rh positive erythrocyte can pass the placenta go to mother whose Rh is negative.
- Mother will produce antibodies and that will pass back to the fetus via placenta
=> Hemolysis
(The infant responds by increasing RBC produ
Helmet" RBC cells in Hemolytic pathologies are called:
Schistocytes
3 types of polycythemia based con cause:
1) Relative polycythemia
- Dehydration-induced hemoconcentration of the blood
2) Polycythemia vera (primary)
-Associated with neoplastic transformation of bone marrow cells (older adults around 60)
3) Secondary polycythemia (most common)
- Increased EPO p
Relative polycythemia
History of excessive fluid loss or poor intake
Accompanying manifestations of dehydration
Polycythemia vera (primary:
Neoplatic, nonmalignant condition => Increases RBCs, WBCs, Platelets
Very rare. Only in >60 yrs
Diagnosis includes: absence of hypoxemia, dehydration and presence of leukocytosis and thrombocytosis.
Without treatment, 50% due within 18 months.
Manifestati
Symptoms of polycythemia vera (primary):
Due to increased BV, viscosity, and thrombosis
a) Headache
b) Light headedness (dizziness)
c) Intense, painful itchiness, particularly after hot bath (mast cell in skin)
d) Red face
e) Fatigue
f) Dyspnea (shortness of breath)
g) Thrombophlebitis (venous b
Secondary Polycythemia:
Most COMMONLY an appropriate physiologic response (due to increased EPO):
- Individuals living at high altitude
- Individuals with COPD
- Individuals with CHF
- Smokers (due to increased CO levels in blood)
Also in renal tumor cell patients and patients w
Increased Hb affility for O2:
Move left
Hemoglobin Rainier
Hemoglobin Chesapeake
Hemoglobin with an increased affinity for Oxygen caused increased circulating RBC because:
It's harder to load off all of the oxygen (check answer)
Major complications of polycythemia:
1) Increased blood viscosity
2) Risk of thrombi
Allogeneic vs. Autologous bone marrow transplant:
1) Allogeneic is from a bone marrow donation and it is less likely to develop the same primary cause of transplant. (more successful in curing leukemia)
2) Autologous is using their own bone marrow after processing. It will not reject for sure and graft-v
Quantitative alterations of leukocytes:
1) Bone marrow dysfunction (increase or decrease)
2) Premature destruction of cells in the circulation (decrease)
3) Alterations originate in the circulation or lymphoid organs in response to invasion by infectious microorganisms (increase)
Qualitative alterations of leukocytes include:
Leukemia and multiple myeloma
Leukocytosis:
Higher than normal (4,000-11,000/uL)
Caused by:
- Invading microorganisms
- Strenuous exercise
- Emotional changes
- Temperature
- Anesthesia/Sugery/Pregnancy/Drugs
- Pathologic conditions (malignancies and hematologic disorders)
Leukopenia:
Fewer than normal
Not normal or beneficial
< 1000uL, risk of infection increased
< 500, life-threatening
Caused by: radiation, anaphylatic shock, autoimmune disease (SLE), immune deficiencies, certain chemotherapy agents
Neutrophilia (Granulocytosis)
> 7,500/uL (>100,00 can cause occlusion)
Infection and inflammation
Neutropenia (Granulocytopenia)
Reduction. (<2,000/uL)
Occur with severe, prolonged infections when production can't keep up with demand
Eosinophilia
Cause:
1) Parasitic infection
2) Allergic disorders
Eosinopenia
Caused by eosinophil migration into inflammatory sites and therefore out of blood stream
Basophilia
Rare
Generally seen as a response to inflammation and immediate hypersensitivity reactions.
Contain histamine that is released during an allergic reaction
Basopenia
In hyperthyroidism, acute infection, long-term therapy with steroids
Monocytosis
Occurs during the late or recuperative phase of an infection when macrophages are needed to phagocytize surviving microorganisms and debris
Also in chronic infections such as tuberculosis and subacute bacterial endocarditis
Monocytopenia
Rare occurence but has been identified with hairy cell leukemia and prednisone therapy
Lymphocytosis
Rare in acute bacterial infections
Mostly in acute viral infections, particularly those caused by Epstein-Barr virus (cause infectious mononucleosis)
Lymphocytopenia
Caused by:
1) Abnormalities of production associated with neoplasms and immune deficiencies
2) Increased destruction by drugs, viruses or radiation
3) NO apparent cause
Major problem with people with AIDS
Infectious Mononucleosis:
Acute infection of B cells
Agent: Epstein-Barr virus (B has receptors for it)
Peak at 15-19 (kissing)
Common triad of symptoms for Infectious Mononucleosis:
Fever
Sore throat
Cervical lymph node enlargement
Mononucleosis in >40 years:
Cytomegalovirus infection is more common than EBV
Diagnosis of Infectious Mononucleosis:
-Monospot agglutination test that is positive for Heterophil Antibodies.
- Heterophil antibodies are human IgM capable of agglutinating RBC of non-human species
- False positive may occur on rare occasions with other conditions (e.g. SLE, hepatitis, rubel
Leukemia
Malignant disorder of the blood and blood-forming organisms causing an accumulation of dysfunctional cells and a loss of cell-division regulation.
- Uncontrolled proliferation of leukocytes which results in an overcording of the bone marrow causing decrea
Lymphoma
Tends to localize in lymph tissue but is often disseminated to other sites at the time of the diagnosis.
Enlarged, nontender lymph nodes are a common finding in lymphoma
Plasma cell myeloma
Is also called Multiple myeloma
Tends to form localized tumors in body structures
Acute vs Chronic Leukemia
Acute: rapid growth of immature blood cells
Chronic: slow growth of more-differentiated cells
Acute and Chronic of Myeloud and Lumphoid
Acute Leukemia:
- Acute myelocytic leukemia (AML)
- Acute lymphocytic leukemia (ALL)
Chronic leukemia:
- Chronic myelocytic leukemia (CML)
- Chronic lymphocytic leukemia (CLL)
Clinical manifestations of leukemia are due to:
1) Bone Marrow Suppression
2) Organ dysfunction secondary to leukemic infiltration
Bone Marrow Suppression
- Anemia: pallor, fatigue, dyspnea
- Thrombocytopenia: Patechiae (pinpoint-sized hemorrhages of small capillaries in the skin or mucous membranes), bleeding gums, hematuria, prolonged bleeding time
- Leukopenia: frequent recurrent infections and fever
Organ dysfunction secondary to leukemic infiltration:
Weight loss
Anorexia
Lymphadenopathy
Hepatomegaly and Splenomegaly
Bone pain
CNS dysfunction
Alterations of lymphoid function include:
1) Lymphadenopathy
2) Malignant lymphomas
Lymphadenopathy is characterized by
Enlarged LYMPH NODES
Localized lymphadenopathy usually indicates drainage of an inflammatory
Generalized lymphadenopathy is usually associated with a malignant or nonmalignant disease (not acute infection)
=> More in adults than children
Malignant lymphomas are
Malignancies of lymphocytes, histiocytes, and their precursors/derivations of lyphoid tissues.
Major types are Hodgkin disease and non-Hodgkin lymphoma
Classification of lymphoma:
1) Hodgkin lymphoma: presence of Reed-Sternberg cells
2) B-cell neoplasms: non Hodgkin, multiple myeloma
3) T-cell and NK: non-Hodgkin lymphoma
Reed-Sternberg cells:
Giant, malignant, multinucleated white blood cells. (B lymphocytes or macrophages)
Hallmark of Hodgkin lymphoma
Ann Arbor staging is the staging system for lymphomas:
1) Involvement of a single lymph group or lymphoid structure
2) 2 or more lymph node groups on the same side of the diaphragm
3) Lymph node groups on both sides of the diaphragm
4) Extranodal sites beyond those designated
Multiple myeloma is a:
Neoplasm of B cells (immature plasma cells) and mature plasma cells
Multiple myeloma is characterized by multiple malignant tumor masses of
Plasma cells that are scattered throughout the skeletal system and are sometimes found in soft tissue
Cause of multiple myeloma:
Unknown but genetic factors and chronic stimulation of the MPS by bacteria, viral agents, and chemicals has been suggested
Recurrent infections of multiple myeloma is because:
SUppression of the humoral immune response
Major clinical manifestations for multiple myeloma:
1) Recurrent infection: humoral immune suppression
2) Renal disease: as a result of Bence Jones protein proteinuria (monoclonal antibodies involved in renal amyloidosis and renal failure)
- see in pee or blood
3) Infiltration of bones: vertebrae, ribs, sk
Treatment for multiple myeloma:
Chemotherapy (choice)
Radiation, plasmapheresis
Marrow transplant
Thalidomide
Survival for multiple myeloma
2-3 years with chemotherapy
Burkitt Lymphoma
- B-cell lymphoma that accounts for 30% of childhood lymphoma
- Epstein-Barr virus is associated with 90% of Burkitt lymphoma
- African and American type
African vs American types of Burkitt
1) African: involves jar and facial bones. Can be treated successfully with radiation therapy and cyclophosphamide
2) American: involves the abdomen and extensive marrow replacement. More resistant to treat
Acute Myeloid Leukemia
#NAME?
Chronic Myeloid Leukemia
- Affects adults primarily
- Malignant granulocytes that carry a unique chromosomal abnormality, the PHILADELPHIA CHROMOSOME
- Unusual among human cancers because of SINGLE ONCOGENE can cause malignant state
- Insidious onset
- 3 phases: chronic, accelera
Acute Lymphoblastic Leukemia:
- All affects children primarily (3-7) (2nd most common cause of death)
- Highly curable in pediatric population but less so in the adult population (5-years-survival-rate is 80% vs. 30%-50%)
- Associated with transformation of precursor "blasts" in the b
Chronic Lymphoblastic Leukemia:
- Neoplasm of mature, peripheral B cells (95%) of all cases (defective apoptosis)
- Affects adults primarily (30% of all cases of leukemia in the US)
- Insidious onset
- Asymptomatic
- Stem cell transplantation or administration of monoclonal antibodies
Thrombosis
Formation or presence of blood clot within a blood vessel
(if detaches, will become embolus)
Hemostasis involves 3 key stages:
1) Vasospasm
2) Platelet plug formation
3) Activation of clotting cascade to form fibrin clot (coagulation phase)
Clot activation is initiated via 2 mechanisms:
1) Intrinsic Pathway
- Blood comes into contact with altered vascular endothelium
-The clotting pathway begins with chemicals intrinsic to the blood
- Hagemen factor (factor XII) contacts collagen
2) Extrinsic pathway
- Tissue thromboplastin (factor III)
Normal platelet count is
150,000 - 400,000/ mm3
Bleeding time:
Normal bleeding time is: 2-9 minutes
Prothrombin Time (PT) is 12-15 seconds (test for extrinsic pathway)
Partial thromboplastin time (PTT) is 25-35 seconds (test for intrinsic pathways)
Antithrombin can bind and neutralize the activity of
Thrombin. (Heparin increases the activity of antithrombin)
Fibrinolysis:
1) Dissolution of the clot is called fibrinolysis
2) Begins with the activation of the proenzyme PLASMINOGEN by thrombin and tissue plasminogen activator (t-PA)
3) Activation of plasminogen produces plasmin, which begins digesting the fibrin strands and e
Altered hemostasis can be due to:
1) Vascular disorders
2) Platelet disorders
3) Coagulation disorders
Vascular disorders
1) Inflammation (allergic pupura)
2) Structural abnormalities (collagen diseases)
3) Weakened vessel walls (telangiectasia)
Platelet disorders
1) Thrombocytopenia (too few)
2) Thrombocythemia (too many)
3) Dysfunctional (abnormal platelet adhesion/aggregation)