Hemolytic Disorders (Exam 1) Flashcards
Ischemic stroke
arteries to the brain become narrowed or blocked
two types of ischemic strokes
thrombotic stroke and embolic stroke
thrombotic stroke
clot forms in the arteries that supply blood to the brain
embolic stroke
clot forms elsewhere and travels to the arteries in the blood stream
von willebrand disease
most common inherited bleeding disorder
ability to form a platelet plug
type 1 von willebrand disease
most common, usually mild to moderate
type 2 VWF
moderate to severe
type 3 VWF
rare and severe
factor XI deficiency
typically genetic, over 200 distinct pathogenic variants are known
Hemophilia
bleeding disorder caused by deficiency in specific clotting factor
X linked recessive
Hemophilia A
deficiency in clotting factor VIII
Hemophilia B
deficiency of clotting factor IX
Pathogenic bleeding
due to a genetic or use of a drug
can effect primary or secondary hemostasis
drugs for pathogenic bleeding
antiplatelets and anticoagulants
Stoke symptoms (5)
trouble with speaking/understanding
paralysis/numbness of the face, arm and leg
trouble with sight in one/both eyes
headache
trouble with walking
stroke
blood supply to part of the brain is interrupted or reduced
hemorrhagic stroke
a blood vessel in the brain leaks and breaks
two types of hemorrhagic stroke
intracerebral hemorrhage
subarachnoid hemorrhage
intracerebral hemorrhage
bleeding occurs in the brain
subarachnoid hemorrhage
bleeding occurs in the space between the surface of the brain and the skull
Hematopoiesis
Development of blood elements from bone marrow stem cells
Transient ischemic attack (TIA)
temporary block of blood flow to your brain
Myocardial Infarction
heart attack
clot occurs in coronary artery
Cytokines
Small signaling proteins
Deep Vein thrombosis
only half people show signs and symptoms
swelling of the leg alone in the vein
pain/tenderness while standing or walking
Production of RBCs
Hypoxia –> Kidneys produce EPO
EPO –> Erythropoiesis in bone marrow
Pulmonary embolism
clot that travels to the lung
started as DVT
shown on an angiogram
treatment for pulmonary embolism
heparin or coumadin
Reticulocytes
Immature RBCs
heparin
inactivates thrombin
coumadin
interferes with vitamin K
prevents new clots from forming
Erythrocytes
Mature RBCs
arterial thrombi
formed under high pressure
more platelet rich
venous thrombi
formed under low pressure
more fibrin rich
Virchow’s triad
three factors that increase risk of pathogenic thrombus:
endothelial injury
abnormal blood flow
hypercoahulability
primary erythrocytosis
disorder of the bone marrow
Polycythemia vera
endothelial injury
main influence on thrombus formation in the heart and the arterial circulation
endothelial injury is caused by
hypertension, hyperlipidemia, high glucose in diabetes mellitus, traumatic vascular injury
abnormal blood flow
the state of turbulence and stasis rather than laminar flow
abnormal blood flow is caused by
hyperlipidemia, aneurysm, MI, cardiac arrhythmia, immobility and paralysis
hypercoagulability
increased tendency to develop blood clots due to an acquired or inherited factor
two types of hypercoagulability
inherited (primary)
acquired (secondary)
types of acquired hypercoagulability
cancer
smoking
pregnancy
medications such as heparin, estrogen
types of inherited hypercoagulability
Factor V Lieden
Protein C or S deficiency
Factor V lieden
point mutation in the gene for Factor V
causes resistance to the anticoagulant effects of activated protein C
examples of endogenous anticoagulants
antithrombin
Protein S
Protein C
Tissue factor pathway inhibitor
antithrombin
inactivates factor IIa (thrombin) and Xa
Protein S
cofactor for protein C
Protein C
inactivates factors Va and VIIIa
Tissue factor pathway inhibitor
inhibits the tissue factor VIIa and Xa
coagulation
process of forming a blood clot in response to injury
Hemostasis process (3 steps)
- vasoconstriction
- formation of a platelet plug
- formation of a clot (thrombus)
primary hemostasis
formation of a weak platelet plug
secondary hemostasis
formation of a thrombus which helps stable the platelet plug
embolism
obstruction of blood vessel by a foreign substance
thromboembolism
clot breaks off, travels through circulation and gets stuck in a small blood vessel
fibrinolysis
breakdown of a clot
what does damages tissue release and what does it do?
releases plasminogen activator (tPA)
converts plasminogen to plasmin
what does plasmin do?
breaks down fibrin and dissolves the clot
coagulation cascade two pathways
- extrinsic
- intrinsic
extrinsic pathways
external trauma that causes blood to leave the circulatory system (bleeding)
intrinsic pathways
activated by trauma inside the vascular system
extrinsic players
factor 7 and 10
intrinsic players
factors 8-12
where do the extrinsic and intrinsic pathways converge?
at factor x
“common pathway”
what does factor X do?
converts prothrombin to thrombin
under normal physiological conditions, there is a balance between? what does the balance prevent?
procoagulant system and anticoagulant system
prevents excessive blood loss
normal platelets
150,000-450,000 per uL
thrombocytopenia
low platelets ( less than 150,000)
when there is less than 50,000 per uL of platelets,
bleeding occurs easily
when there is less than 20,000 per uL
spontaneous bleeding can occur in the absence of injury
examples of decreased platelet production
bone marrow disorders
liver disease
examples of increased platelet destruction
drug associated immune thrombocytopenia
example of platelet trapped in the spleen
splenomegaly (enlarged spleen)
thrombocytosis
high platelets (over 450,000 per uL)
what could thrombocytosis be due to?
cancer, removal of the spleen or genetic mutations
formation of the platelet plug (3 steps)
- platelet adhesion
- platelet activation
- platelet aggregation
platelet adhesion
exposes collagen and VWF
platelet activation
platelets undergo an irreversible change in shape to increase surface area and secrete granules
platelet aggregation
circulating fibrinogen binds to GP receptors on platelets and cross links them forming the platelet plug
after the vessel wall is broken, what is the blood exposed to?
collagen and VWF
what responds to the injury and what does it release?
neutrophils and macrophages
Platelet Activating factor
Platelet activating factor
activates platelets and causes them to stick to the vessel wall at the site of injury
what do activated platelets release?
ADP, serotonin and thrombaxone A2
what is the end result of blood clotting?
vasoconstriction
when there is no injury, how does the intact epithelium prevent platelet activation?
separating the blood from collagen
secreting NO and prostaglandin I2
CD39
what does NO and PGI2 do?
inhibit platelet aggrergation
what does CD39 do?
breaks down ADP in the blood which would normally promote platelet aggregation
Hemostasis
forming clots in the walls of damaged blood vessels and preventing blood loss while maintaining blood in a fluid state
How does hemostasis stop bleeding?
constrict blood vessels and insoles platelets
platelets
anucleate cells found in blood
How does a break in the skin close again?
- hemostasis
- inflammation
- proliferation
- remodeling
splenomegaly
enlarged spleen
higher risk of rupturing, can lead to life threatening bleeding
hyperslenism
spleen is overreactive, removing too many blood cells too quickly
leads to cytopenia
cytopenia
shortage of blood cells
congestive splenomegaly
spleen becomes enlarged and engorged with blood due to impaired blood flow through the splenic vein
infiltrative splenomegaly
enlarged spleen caused by foreign cells invading the spleen
Lymphoblastic Lymphoma
clone of immature T cells that become malignant in the thymus
Multiple Myeloma (MM)
malignant proliferation of plasma cells that infiltrate bone marrow
aggregate into tumor masses in skeletal system
Non-hodgkin Lymphoma
diverse group of lymphomas linked to chromosome translocations
Risk factors of non-hodgkins lymphoma
older, male, white, having immune disorders, etc.
Burkitt Lymphoma
most common NH lymphoma in children
very fast growing tumor on jaws and facial bones
Hodgkin Lymphoma
presence of Reed-Sternberg cells in the lymph nodes
Prescence of Reed-Sternberg cells in the lymph nodes are necessary for
diagnosis but not specific to Hodkins lymphoma
Symptoms of Hodgkin Lymphoma
fever, weight loss, night sweats, pruritus
can adult Hodgkin lymphoma be cured?
yes with early diagnosis and treatment
Malignant Lymphomas
diverse group of neoplasms that develop from the proliferation of malignant lymphocytes in the lymphoid system
how are malignant lymphomas classified?
REAL classification
the two major categories of malignant lymphomas
Hodgkins Lymphoma
Non-Hodgkin Lymphoma
Lymphadenopathy
enlarged lymph nodes that become palpable and tender
Two types of Lymphadenopathy
local and general
local lymphadenopathy
drainage of an inflammatory lesion located near the enlarged node
general lymphadenopathy
occurs in the presence of malignant or nonmalignant disease
most common way to detect a lymph node
ultrasonography
chronic leukemias examples
chronic myelogenous leukemia
chromic lymphocytic leukemia
chronic myelogenous leukemia
too many blood cells made in the bone marrow
chronic lymphocytic leukemia
too many immature lymphocytes
slow progression
most common adult leukemia in the western world
chronic lymphocytic leukemia
most common adult leukemia
acute myelogenous leukemia
acute leukemias examples
acute myelogenous leukemia
acute lymphocytic leukemia
acute myelogenous leukemia
too many myeloblasts
acute lymphocytic leukemia
too many lymphoblasts
mostly in children
treatment for acute leukemia
chemotherapy
acute leukemias are manifested by
bone marrow depression, fever, anorexia, neurologic symptoms
Leukemias
malignant disorder of the blood and blood forming organs
excessive accumulation of leukemic cells
Pancytopenia
cells crowd bone marrow
acute leukemia
presence of undifferentiated/immature cells
usually blast cells
chronic leukemia
predominant cell is mature but does not function properly
Lymphocytosis
increase in the number of proportion of lymphocytes in the blood
includes acute viral infections: epstein barr virus
Lymphocytopenia
decrease in the number of circulating lymphocytes in the blood
quantitative disorders
increases or decreases in cell numbers
bone marrow disorders/ response to infectious organisms
leukocytosis
normal protective physiologic response to stressors
leukopenia
not normal/beneficial
a low white count predisposes a patient to infections
polycythemia vera
rare cancer of the blood producing cells of bone marrow
mutation in the JAK2 gene
secondary erythrocytosis
due to increased EPO production
what can lead to overproduction of EPO?
chronic low oxygen levels can cause a compensatory increase in hemoglobin production
renal tumor
drugs (testosterone, Epotein)
erythrocytosis
increase in the production of RBCs leading to elevated hemoglobin
signs/symptoms of erythrocytosis
hypertension, frequent nosebleeds/bruising, pruritus
Sickle Cell Disease
2 alpha globin chains and 2 mutated beta global chains due to a non-conservative missence mutation
sickle cell carrier
has one copy of the gene and one normal gene
no health problems
reduced risk of malaria
autosomal recessive disease
two copies of the altered hemoglobin gene
SCD
Sickle cells can get stuck in small capillaries and lead to
vase-occlusion, ischemia and pain crisis
sickling of cells in SCD is due to
deoxygenated hemoglobin becoming aggregated –> loss of normal shape
how much folate can be stored in the liver?
1 month
how much B12 can be stored in the liver?
large quantities
3000-5000mcg
Sideroblastic anemias
rare disorder in which bone marrow produces abnormal RBCs called ringed sideroblasts
microcytic anemia
plasma iron levels are normal to high
pathophysiology of sideroblastic anemias
abnormal heme synthesis and inability to incorporate iron into heme
genetic/aquired dysfunction of one of the many enzymes in heme biosynthesis pathway (Shaman pathway)
Thalassemias
genetic, microcytic anemia
abnormal or absent production of alpha or beta globin
Alpha thalassemia
alpha globin gene deletion resulting in reduced or absent production
beta thalassemia
point mutations in beta globin gene
beta thalassemia minor
mild, asymptomatic
beta thalassemia intermedia
mild to moderate symptoms
beta thalassemia major
severe, complete absence of beta chains
lifelong blood transfusions
Hemochromatosis
iron overload occurs in the body, causing iron toxicity
storage of iron in the heart, liver, pancreas and causing organ failure
gene involved in hemochromatosis
HFE gene
affects pattern of iron absorption
ferritin
protein that stores iron
transferrin
protein that transfers iron in the blood
about how much dietary iron per day is required
10-20 mg
Porphyrias
heme proteins are constantly synthesized and degraded
cells do not convert porphyrins to heme in a normal manner
rate limiting step in porphyrias
succinyl CoA and glycine –> delta aminolevulinic acid
ALA synthase is the enzyme
symptoms of porphyria
formation of superoxide radicals leads to
skin damage from exposure to light
two erythrocyte disorders
anemia (low Hb)
erythrocytosis (high Hb)
two leukocyte disorders
leukopenia (low WBC)
leukocytosis (high WBC)
two thrombocyte disorders
thrombocytopenia (low platelets)
thrombocytosis (high platelets)
two disorders of coagulation
hemorrhage (excessive bleeding)
thrombosis (blood clot)
hematopoiesis
development of the formed elements of blood from bone marrow stem cells
hematopoietic cells are found in the
peripheral blood and in bone marrow
reticulocytes
immature RBCs
make up 1-2% of circulating RBCs
erythrocytes
mature RBCs
circulate for 120 days and destroyed by macrophages
what has a higher affinity for heme than oxygen?
CO
at higher elevations, what has a higher affinity to heme?
myoglobin because there is less oxygen so more is trying to go to the tissues
myoglobin has a higher binding affinity in the _____ while hemoglobin has a higher binding affinity in the ______
tissues
lungs
hemoglobin has a ______ binding affinity for oxygen at high pressure
even lower
what regulates the binding and release of oxygen in Hb
allosteric interactions
does the mother or baby have a higher affinity for oxygen?
the baby
fetal hemoglobin
2 alpha and 2 gamma chains
difference between hemoglobin and fetal hemoglobin
fetal hemoglobin has a serine residue instead of histidine
reduction of 2 positive charges
reduced affinity for 2,3 BFG and increased affinity for oxygen
the lower the P50,
the higher the binding affinity
