Blood Disorders Flashcards
(78 cards)
1
Q
Where are Eryhrocytes derived from?
A
-Erythroblasts
2
Q
Maturation of RBC is stimulated by what? And where is it synthesized?
A
- Stimulated by erythropoietin
- Synthesized in Kidney
3
Q
Define Erythropoisesis
A
-Formation of RBCs
4
Q
Describe the structure of the Hemoglobin Group
A
-Four polypeptide chains attached to heme unit surrounding an atom of iron that binds oxygen
5
Q
Binding of O2 to hemoglobin forms what?
A
-Oxyhemoglobin
6
Q
When O2 is not bound to hemoglobin is called?
A
-deoxyhemoglobin
7
Q
What is an oximeter?
A
-Device measures oxygen saturation
8
Q
What state of iron does O2 bind to?
A
- Fe2+ (ferrous iron)
- Cant bind to Fe3+ (ferric form)
9
Q
When Hemoglobin releases O2 at the tissues it sometimes gets oxidized to Fe3+
A
- Methemoglobin (Fe3+)
- Can’t bind to to O2
10
Q
What enzyme reactivates hemoglobin?
A
- methemoglobin reductase
- Converts Fe3+ to Fe2+
11
Q
Disorder: Methemoglobinemia
A
-Deficiency in Methemoglobin reductase
12
Q
What is Anemia?
A
-Reduction in the total number of erythrocytes in the circulating blood or in the quality of quantity of hemoglobin.
13
Q
Possible causes of Anemia
A
- Impaired erythrocyte production
- Acute or chronic blood loss
- Increased Erythrocyte destruction
- Combination of the above
14
Q
Types of Anemia’s
A
- Macrocytic-Normochromic
- Microcytic-Hypochromic
- Normocytic-Normochromic
15
Q
Description of Macrocytic-Normochromic Anemia & two examples
A
- Abnormally large red blood cells
- Results in insufficient # of RBC
- Caused by defective erythrocyte precursors
- –>Decrease DNA synthesis
- Examples : Pernicious Anemia & Folate Deficient Anemia
16
Q
Pernicious Anemia
A
- Deficiency of Vitamin B12 due to the absence or lack of intrinsic factor
- Macrocytic-Normochromic Anemia
17
Q
Folate Deficient Anemia
A
- Deficiency of Folate/Folic Acid
- Required for DNA synthesis
- Decrease in Folate acid will result in neural tube defects and colon cancer
- Fortification of foods has lead to a decrease FA deficiency
18
Q
Microcytic-Hypochromic Anemias
A
- Characterized by red blood cells that are abnormally small and contain reduced amounts of hemoglobin
- Related to iron metabolism, porphyrin, heme & globin synthesis.
19
Q
Iron deficiency anemia (hypoferremia)
A
- Microcytic-Hypochromic Anemia
- Most common type of anemia worldwide
- Etiology
- –>Nutritional iron deficiency, chronic blood loss, impaired absorption
- Symptomatic Hb below 7-8 g/dl
- –>Normal males: 13-18 g/dl
- –>Normal females: 12-15 g/dl
20
Q
Role of Hepcidin
A
-Low iron stores=decrease in hepcidin=increase of Ferroportin 1
21
Q
Sideroblastic anemia
A
- Microcytic Hypochromic Anemia
- Group of disorders characterized by abnormal hemoglobin synthesis
- –>X linked (ALAS-E gene) rating limiting step of Hemoglobium
- –>Toxins/drugs=lead, alcohol, chloramphenicol
- –>Deficiency=copper, pyridoxine (vitamin B6)
- Ringed sideroblasts within bone marrow are diagnostic
- called siderblastic because you see these ring shaped
22
Q
Thalassemias
A
- Inherited disorders that result in defective or absent synthesis of the alpha or beta chain of hemoglobin
- Normal chains can’t pair with correct one and cause damage
- Two forms Alpha & Beta
23
Q
Normocytic-Normochromic Anemias
A
- Characterized by red blood cells that are relatively normal in size and hemoglobin content but insufficient in number
- –>Aplastic anemia
- –>posthemorrhagic anemia
- –>Hemolytic anemia
24
Q
Aplastic Anemia.
Mortality and Treatments
A
- Normocytic-Normochromic Anemias
- Stem cell disorder->Bone marrow depression/suppression that leads to pancytopenia (reduction in all our RBCs)
- Can be familial or acquired
- –>2/3 are idiopathic
- –>Exposure to radiation, chemicals, drugs toxins, infection and autoimmune
- rapid progression with a high risk of death
- –>Mortality 65-75%, survival 3-4months <10%
- Treatments include
- –>Identification and avoidance of further toxin exposure
- –>Blood transfusion
- –>Stimulation of hematopoiesis
- –>Bone Marrow Transplants
25
Hemolytic Anemia
- Accerlerated destruction of red blood cells
- -->Extravascular: Spleen
- -->Intravascular: AB & complement
- Autoimmune Hemolytic anemias
- -->Warm autoimmune hemolytic anemia
- -->Cold agglutinin autoimmune hemolytic anemia
- -->Cold Hemolysin autoimmune hemolytic anemia
- Drug induced
26
Warm Autoimmune Hemolytic Anemia
- Warm autoimmune hemolytic anemia
- 50% of cases are secondary to other diseases
- -->Lymphomas, SLE, chronic Lymphocytic leukemia
- Caused by an IgG that binds optimally to RBC at normal body temperature
- In most cases antibodies against the Rh complex
- RBC are removed by the extravascular process
27
Cold Agglutinin Anemia
- Mediated by IgM
- -->Bind optimally to RBC at cold temperatures
- In cold conditions agglutination of RBC in fingers, toes, ears
- -->Prolonged exposure to cold temperatures can obstruct blood flow to these area=gangrene
- Increase temp IgM releases RBC
- RBC are removed by the extravascular process
28
Cold Hemolysin Anemia
- Exposure to cold intravascular hemolysis
- IgG mediated
- Antibodies against P blood group antigen
- Leads to complement activation and destruction of RBC
- Often seen following viral infections
- RBC are destroyed by the intravascular process
29
Anemia of chronic inflammation
- Mild to moderate anemia seen in
- -->AIDs, rheumatoid arthritis, lupus erythematosus, hepatitis, renal failure, and malignancies
- Pathologic mechanisms
- -->Decreased erythrocyte life span
- -->suppressed production of erythropoietin
- -->Ineffective bone marrow response to erythropoietin
- -->Altered iron metabolism
30
Sickle Cell Anemia
- Common hereditary hemoglobinopathy caused by a point mutation in B-globin
- Promotes the polymerization of deoxygenated hemoglobin
- leads to red cell distortion, hemolytic anemia, microvascular obstruction & ischemic tissue damage
- Recessive inheritance
- Sickle cells abnormally shaped
- Life span of sickle cell is reduced
31
Rate & Degree of Sickling
- Deoxygenation increase rate and degree of sickling
- Interaction of HbS with the other types of hemoglobin in the cell (HbA vs HbF)
- Higher mean Cell hemoglobin concentration
- -->dehydration increases sickling
- Intracellular pH
- -->Decrease in pH promotes sickling
- Transit time of red cells through microvascular beds
32
Myeloproliferative RBC disorders
- Polycythemia
- -->Increase portion of RBC to plasma volume
- -->Overproduction of RBC
- Relative polycythemia
- -->Result of dehydration
- -->Fluid loss results in relative INCREASE of RBC and Hb and Hct values
33
Polycythemia
- Absolute polycythemia
- ->primary absolute (polycythemia vera)
- -->abnormality of stem cells in the bone marrow
- -->95% due to mutation in JAK-2
- ->Secondary absolute
- -->Increase in erythropoietin as a normal response to chronic hypoxia or an inappropriate response to erythropoietin-secreting tumors
34
Leukocytosis
-Higher than normal WBC count
35
Leukopenia
-Lower than normal WBC
36
Neutropenia
- Reduction in circulating neutrophils
- causes
- -->Genetics (Kostmann Syndrome)
- -->Prolonged infection
- -->In-effective granulopoiesis
- -->Reduce neutrophil survival
- -->Abnormal neutrophil distribution/sequestration
37
Infectious Mononucleosis (IM)
- Acute, self-limiting, lymphoproliferative disorder of B lymphocytes
- Transmitted by saliva through personal contact
- 85% of cases: Epstein Bar virus (EBV)
- -->B cells have an EBV receptor site
38
Pathogenesis of IM
- EBV infects B-cells
- Antibody response from uninfected B-cells
- Massive CD8+ cytotoxic T cells response against Bcells
- Inflammation in the following tissues
- -->Spleen, lymph nodes, and liver
39
IM symptoms, lab values, diagnostic test, and treatment
- Fever, sore throat, swollen cervical lymph nodes
- >50% lymphocytes and at least 10% atypical lymphocytes
- Monospot qualitative test for heterophilic antibodies
treatment: symptomatic
40
Leukemias
- clonal disorder in that a single progenitor cell undergoes malignant transformation
- Uncontrolled proliferation of malignant leukocytes
- -->Overcrowding of bone marrow
- -->Pancytopenia
41
Types of Leukemia
- Acute lymphocytic leukemia (ALL)
- Acute myelogenous leukemia (AML)
- Chronic myelogenous leukemia (CML)
- Chronic lymphocytic leukemia (CLL)
42
Causes of Leukemia
- Family history
- Congenital Disorders
- Infection
- Environmental Factors
- Drugs
- Chromosomal abnormalities lie CML, inversions and deletions
43
Acute Lymphocytic Leukemia (ALL)
-Least common overall but most common childhood leukemia (80%)
-Higher mortality rates in adults
In children ALL is usually a precursor B-cell
--->80% = Common precursor B cell
-In adults usually a mixture of B and T precursor cells
-Chromosomal abnormalities are very common
44
Acute Myelogenous Leukemia (AML)
- Abnormal proliferation of a Myeloid precursor cell
- Most aggressive and most common
- Overcrowding of bone marrow=leading pancytopenia
45
Clinical Manifestations ALL & AML & Treatment
- Pancytopenia
- -->Anemia, fatigue, abnormal bleeding, fever
- infection
- increases blood viscosity and thrombi
- CNS involvement
- Spleen and liver enlargement
- Treatments:
- -->Chemotherapy (with allopurinal)
- -->Supportive measures: blood transfusion, antibiotics, antifungals, antivirals
- -->Bone Marrow Transplants
- -->5 yr survival reate ALL> AML
46
Chronic Lymphocyitic Leukemia (CLL)
- Common in older adults (70 yrs)
- Almost always a clonal maligancy of B cells
- -->Lymphadenopathy
- -->Supression of humoral immunity (Hypogammaglobullenmia, increased infection with encapsulated bacteria)
- Does not interfere with production of normal cells IN EARLY STAGES
47
Chronic Myelogenous Leukemia (CML)
- Usually diagnosed in adults (67yrs)
- Excessive proliferation of marrow granulocytes, erythroid precursors and megakaryocytes
- Philadelphia chromosome is presence in 95% of cases
- -->ABL-1(9) and BCR (22)
48
Clinical Manifestations of CLL and CML
- CLL
- -->Very slow and insidiously
- -->Infections due to humoral suppression
- -->Fatigue, extreme weight loss, anemia, bleeding
- -->75% 5 yr survival rate
- CML
- -->Painful splenomegaly
- -->Slower progressive phase (asymptomatic)
- -->Accelerated phase (symptoms)
- -->Terminal Phase (similar to AML)
- -->47% 5 yr survival rate
49
Lymphadenopathy
- Characterized by enlarged lymph nodes
- -->Increase in size numbers/ of germinal centers
- -->may be caused by invasion of malignant cells
- -->Endocrine disorders
- -->Lipid storage disease (Gaucher Disease)
50
Malignant Lymphomas
- Diverse group of neoplasms that develop from the proliferation of malignant lymphocytes in the lymphoid system
- includes Hodgkin Lymphoma, Non-Hodgkin Lymphoma, and Burkitt Lymphoma
51
Differences between Leukemia vs Lymphoma
-Both result of a malignant transformation of a cell destined to be a lymphocyte
-Lymphoma: Starts from a lymphatic cell in a lymph node or other part of the lymphatic system
Leukemia: Started from a lymphocytic cell in bone marrow (can also be from derived from a myeloid cell)
52
Hodgkin Lymphoma
-Median age is 38 yrs
-Characterized
--->progression from one group of lymph nodes to another
--->Presence of Reed-Sternberg Cells
--->Development of systemic symptoms
-Appears to be derived from
a B cell line
--->Linked to EBV?
-Reed Sternberg cells in the lymph nodes
--->Secrete IL-10 and TGF-B
-Subcategorized into two main types
--->Classical Hodgkin lymphoma
--->Nodular lymphocyte predominant Hodgkin lymphoma
53
Non-Hodgkin Lymphoma
- Generic term for diverse group of lymphomas
- Can originate in B cells (85%) or T/NK cells
- Occurs 3x more frequently than Hodgkin's
- -->Tend to be more severe as well
- Average age of diagnosis is 67 yrs
- Unpredictable & poor prognosis
- Linked to
- -->Chromosome translocations
- -->Genetics
- -->Viral and bacterial infections
- -->Environmental agents
- -->Immunodeficiencies
- -->Autoimmune disorders
54
Burkitt Lymphoma
-Translocation / overexpression of C-MYC
55
African-Burkitt Lymphoma
- Most common childhood non-hodgkin lymphoma
- A very fast growing tumor of the jaw and facial bones
- Epstein Barr virus is found in nasopharyngeal secretions of 90% individuals
- -->B cell line tumor
- -->EBV induces Burkitt Lymphoma translocation
56
Non-African (Sporadic) Burkitt Lymphoma
- Very Rare
- Unusually develops in the abdominal lymph nodes
- Extensive bone marrow invasion
- Not associated with EBV
- Much more resistant to treatment
57
Multiple Myeloma
- B-cell malignancy of terminally differentiated plasma cells
- Median age of onset is 71 yrs
- Neoplastic cells reside in the bone marrow and are rarely seen in circulation or other tissues
- The tumor may be solitary or multifocal
- Cause is unknown
- Majority of plasma cells have chromosomal abnormalities (translocation)
- -->Ig heavy chain (14) relocates and disrupts cyclins, oncogenes, fibroblast growth factors receptors
- Produce abnormal large amounts of IgG called M protein
58
Clinical Manifestations & Treatment of Multiple Myeloma
```
-Clinical manifestations:
>Cortical and medullary bone loss
--->Skeletal pain/fractures
--->Paraneoplastic syndrome
>Anemia/thrombocytopenia/Immunosuppression
>Hyperviscosity of body fluids
-Treatment
>Chemotherapy/radiation
>plasmapheresis
>Bone marrow transplant
```
59
5 steps of clots
```
1-Vessel spasm
2-Formation of the Platelet Plug
3-Blood Coagulation
4-Clot Retraction
5-Clot Dissolution or Lysis
```
60
Explain what is happening in Vessel Spasm
- Due to both local and humoral mechanisms of Smooth Muscle & Thromboxane A2 (TXA2)
- Prostacyclin is released from platelets to prevent platelet adhesion and vasodilation in uninjured area.
61
Explain what is happening in Platelet Plug
1-Injured endothelium release Von Willebrand factor (vWF)
2-vWF binds to receptors on platelets
3-Atrracts platelets and allows them bind to collagen
4-As the platelets adhere, they release ADP and (TXA2)
5-Attract more platelets leading to platelet aggregation
6-GPllb/llla receptors on platelets bind fibrogen and platelets link together
62
Coagulation pathways
Slide 25 Blood disorders #2
63
Control of Hemostatic Mechanisms
```
-Antithrombotics
>Antithrombin III
--->Protease inhibitor; inhibits thrombin and factor Xa
--->Heparin greatly increase activity
>Tissue factor pathway inhibitor (TFPI)
--->blocks effects of tissue factor
>Protein C
--->Inhibits factor V and VIII
```
64
Clot retraction
1-Within 20-60 mins following clot formation actin and myosin molecules in platelets contract
2-Pulls the clot together and pushes any serum in the clot out causing it to shrink
65
Clot Lysis
1-Process of clot lysis is called fibrinolylsis
2-Plasminogen gets converted into plasmin
3-Plasmin slowly dissolve fibrin strands
4-Circulating plasmin is rapidly degraded by a2-plasmin inhibitor
5-Allows for tissue healing and regeneration
66
Thrombocytopenia
- Platelet count x<100,000/mm^3
- --> x<50,000/mm3-hemorrhage from minor trauma
- --> x<15,000/mm3-spontaneous bleeding
- --> x< 10,000/mm3-spontaneous severe bleeding
- Causes:
- -->Hypersplenism, autoimmune disease, hypothermia, and viral or bacterial infections
- --> Congenital (relatively rare)
- -->Drug Induced (heparin)
67
Heparin-Induced Thrombocytopenia
- 4% of patients treated with heparin develop a transient thrombocytopenia (2-5 days)
- Immune reaction directed against a complex of heparin and platelet factor 4
- Antibodies bind to platelet factor 4 forming immune complexes that activator other platelets
- Greater than 50% reduction in circulating platelets
- Increased risk for thrombosis formation
68
Slide 34
Blood disorders II
69
Immune Thrombocytopenic Purpura (ITP)
- Acute form develops after viral infections
- Large amounts of antibodies are produced against an antigen
- Formation of immune complexes in the blood
- Resolve usually in 1-2 months
- Chronic form is autoimmune in nature
- IgG auto antibody targets platelet glycoproteins
70
ITP Manifestations and Treatment
- Manifestations
- -->Petechiae and purpura, may progress to major hemorrhage
- -->Chronic form can be problematic in pregnant women
- Treatment
- -->Immunosuppressive therapy
- -->Splenectomy
71
Thrombotic Thrombocytopenic Purpura (TTP)
- A thrombotic microangiopathy
- -->Platelets aggregate, form microthrombi, and cause ooclusion of arterioles and capillaries
- Chronic relapsing TTP
- Acquired idiopathic TTP
- Both types are due to dysfunction of the plasma metalloprotease ADAMTS1S
- -->Responsible for breakdown of large vWF into smaller molecules
72
Essential (primary) Thrombocythemia
- Characterized by platelet counts x>400,000/mm3
- Myeloproliferative disorder of platelet precursor cells
- -->Megakaryocytes in the bone marrow are produced in excess
- -->Often Associated with Janus Kinase 2 (JAK2) gene defects
- Microvasculature thrombosis occurs
73
Secondary Thrombocythemia
- Splenectomy
- Reaction to inflammatory conditions or neoplasia
- Thrombopoietin receptor defects
74
Alterations of Coagulation
-Vitamin K deficiency
--->Synthesis and regulation of prothrombin, the prothrombin factors (II, VII, XI, and X) and proteins C and S (anticoagulants)
-Liver Disease
>Causes broad range of hemostasis disorders
--->Defects in coagulation, fibrinolysis, and platelet number and function
75
SLide 442
Blood Disorders II
76
Slide 42
Blood Disorders II
77
Inheriited Coagulation and Platelet Disorders
- Hemophilia A (Classic hemophilia)
- -->Most common (85%)
- -->X linked recessive
- --> Deficiency of Factor VIII
- Hemophilia B (Christmas disease)
- -->X linked recessive
- -->Deficiency of Factor IX
- -->A and B are clinically indistinguishable
78
Von Willebrand disease
- Deficiency of vWF
- Four types (20 variants)
- vWF forms complex with Factor VIII and helps stabilize it
- Promotes platelet adhesion
- People with this have a high risk of severe bleeding
