Lecture 5.1: blood Flashcards
What are the main types of blood disorders?
1) Red Cells
2) White Cells
3) Clotting: Platelets or factors
Red cell disease: What are the 3 ways you can have an issue?
1) Loose your RBC’s > bleeding
2) Kill your RBC’s > hemolysis
3) Stop making RBC’s > decreased production
What are the two main types of anemia? What can each cause?
1) Acute:shortness of breath, organ failure, shock
2) Chronic: Pallor, fatigue, presyncope > syncope
-Severe and congenital: growth retardation, bone deformities due to reactive marrow hyperplasia
1) The growth factor responsible for making new RBC’s is ________________.
2) List 3 ways to measure iron
1) erythropoietin (EPO) (from kidneys)
2) Iron level, iron binding capacity, ferritin
List and describe 3 ways to measure red blood cells
1) Hgb/Hematocrit both measure the Hg directly
2) MCV: “mean corpuscular volume”
-Helps distinguish the size type of disease, which is really useful
3) Reticulocyte count: measures the young cells
Helps distinguish between hemolytic and agenerative anemia
RBC blood tests:
1) What are the 2 forms of bilirubin? What does a bilirubin test help differentiate?
2) What can folate and B12 deficiencies cause?
1) Conjugated and uncongigated bili
-Hemolytic anemia
2) Macrocytic anemia
True or false: Hemoglobin is relative
True
1) What should you always measure with hemoglobin labs?
2) Why?
1) This is one lab you should always measure the change of
2) Some people run high or low, but what matters is an abrupt change
When the onset of anemia is slow (i.e. chronic), what are 2 things that happen? What do these do?
1) O2 deficit leads to increased cardiac output, respiratory rate
2) and “red cell 2,3-diphosphoglycerate (DPG), which enhances the release of 02 from hemoglobin
-This adaptive change helps compensate for chronic anemia
1) More than ____% blood loss leads to shock and is often fatal.
2) In acute blood loss like this, will hemoglobin read as low right away? Why/ why not?
3) What happens over the next few days?
1) 20%
2) At first will not read as low bc although you’ve got less blood in your body, the concentration of Hgb in the blood is normal throughout
3) Over the next few days, hemodilution begins and the full effect of anemia will evince itself
(A similar effect occurs in trauma once IV fluids are given to trauma patient; initial Hgb upon arrival will be normal)
1) Chronic blood loss gradually depletes ____ stores.
2) Why does chronic blood loss lead to chronic anemia of underproduction?
1) iron
2) You can’t make proper Hgb without iron
Chronic bleed will demonstrate what 3 things? Why?
1) Low serum iron – b/c you don’t have iron
2) High TIBC: bc the body is “trying” to grab on to more iron
3) Low ferritin: bc this is the body’s major storage protein for iron
Chronic bleeding:
1) Why is ferritin low?
2) What is an important implication of high ferritin?
1) Because this is the body’s major storage protein for iron
(One of the best measures of iron)
2) Think anemia of chronic disease
1) RBC’s live ______ days in RBC destruction, the life span is shortened
2) RBC’s are being ________ when they die; this leads to the release of ________________
3) Why is this thing released?
1) 120
2) lysed; unconjugated bilirubin
3) The bili wasn’t able to be conjugated through normal delivery to the liver
What does hemolysis lead to? What should you check?
1) Hemolysis > low 02 > increased EPO > increased reticulocytes being made
2) Therefore, check the reticulocyte count; it will be high in this disease
What are 2 ways to classify the cause of hemolysis?
Intravascular and extravascular
Extravascular hemolysis:
1) What causes it?
2) Where does this often happen, and why does this happen there?
1) Defects that destroy the RBCs with phagocytes
2) Spleen; requires that cells be able to change their shape in order to move through it; when they cannot, they get stuck. This is called “sequestration”
Define sequestration
A process by which the spleen traps cells with diminished deformability and feeds them to macrophages
List 3 findings in extravascular hemolysis
1) Hyperbilirubinemia and jaundice
2) Late-stage, gallstones and cholelithiasis
3) Sometimes splenomegaly
What is the pathway of hemolysis?
1) RBC houses Hgb
2) Hgb breaks down inside cell releasing bili as byproduct + disease causes RBC to not be pliant
3) RBCs stuck in spleen
4) Spleen houses macrophages for just such a purpose
5) Degradation of RBCs lets unconjugated bili into bloodstream
6) Over time, jaundice and gallstones can occur, as can splenomegaly
Intravascular hemolysis:
1) What is it? What can cause it?
2) What does this release? Explain
1) Direct insult to RBC that bursts in the blood stream
-Turbulence from defective heart valve, complement destruction, some toxins to give a few examples
2) Hg is released into the blood, passes into the urine
-Some Hg is processed into hemosiderin which builds in the kidney and then lost in urine as well
What two things do both intra and extravascular hemolysis cause?
1) Increased unconjugated bilirubin
2) Decreased haptoglobin
What is haptoglobin?
A plasma protein that binds free hemoglobin and removes it from circulation; therefore, its levels will fall (it is being used up) when RBCs are being destroyed, as it is in both cases
Hereditary Spherocytosis:
1) What is the inheritance pattern?
2) What does it lead to? What does this cause?
1) Autosomal dominant
2) Intrinsic defect in RBC membrane; spherical, non-deformable cell causes sequestration and destruction in the spleen
Hereditary Spherocytosis:
1) What 2 proteins are mutated? What are both?
2) What do these mutations cause? What are the effects of this?
1) Mutations in ankyrin or spectrin proteins, both structural cell membrane proteins
2) This causes blebs to form at the membrane surface which are then shed
-Little by little, bits of cytoplasm are released until the surface to volume ratio is decreased, forming a sphere
-These spherical RBCs are then destroyed by macrophages in the spleen
Hereditary Spherocytosis:
1) What are 3 clinical features?
2) Is there anemia? Describe
3) What is the Tx?
1) Anemia, splenomegaly, and jaundice
2) Usually anemia is moderate, though patients are prone to infection with parvovirus B19 which causes aplastic crisis
3) Splenectomy (improves the anemia)
Compare HgA to HgF
1) Adult (HgA): Combination of alpha-globin and beta-globin
2) Fetal (HgF): Combination of gamma-globin and alpha-globin
HgA and HgF: By _____________ of age gamma-globin is gradually replaced with beta-globin
six months
1) Explain why sickle cell doesn’t start until 6mo old
2) What specific organ can become enlarged?
3) What do vasoocclusive crises in the body cause?
1) In the womb we have HgF (fetal) instead of HgA (adult). HgF persists in the blood stream until 6 months of age onset 6 mo
2) Splenomegaly
3) Pain
Sickle cell symptoms:
1) What is hand-foot syndrome?
2) What is acute chest syndrome?
3) Can sickle cell cause stroke?
4) How can it cause vision loss/ blindness?
1) Infarct in bones in said regions
2) Sluggish blood flow to inflamed lung > hypoxia
3) Yes
4) Vasoocclusions in the eye; Proliferative retinopathy
Thalassemias:
1) What are they?
2) What do they cause?
3) Can it be lethal? Explain
1) Disorders associated with an imbalance in the production of alpha or beta globin
2) Causes the formation of hemoglobin molecules with an abnormal number of alpha or beta globins
3) These alternate hemoglobins do not bind oxygen efficiently and can be lethal
Alpha thalassemia
1) What does it cause?
2) What is the most common cause of this condition?
3) How many alleles?
1) Reduced or absent synthesis of alpha globin
2) Deletion(s) of one or both alpha globin genes
3) Two different genes for alpha globin, and thus 4 alleles
Beta thalassemia:
1) What does it cause?
2) What is the most common cause of it?
3) How many genes and alleles?
1) Reduced or absent synthesis of beta globin
2) Single-base pair substitutions that result in proteins that have either reduced activity, altered activity, or no activity at all
3) One gene with two alleles
Alpha Thalassemia:
1) What is it?
2) What happens once 3 or more alpha-globin chains are lost?
3) What does this lead to?
1) Destruction of 1,2,3, or 4 alleles that code for alpha-globin
2) The cell experiences a vitally low amount of alpha-globin, so the remaining beta-globin pairs into a tetramer
3) Formation of its own tetramer beta-4 in adults, and gamma-4 in infants
Alpha Thalassemia: Infants will build up tetramers of gamma-globin until when?
6 months of age
Both tetramers involved in alpha thalassemia have high affinity for oxygen, so what does this cause?
They won’t let it go
Hb H (B4) disease:
1) What is it?
2) Why does it develop?
1) A moderately severe hemolytic anemia develops because of the gradual precipitation of the Hg H in the erythrocyte (type of Alpha Thalassemia)
2) This leads to the formation of inclusions in the mature red blood cell, and the removal of these inclusions by the spleen damages the cells, leading to their premature destruction.
A child with untreated B-thalassemia major may look like what? Why?
Prominent cheekbones and protrusion of upper jaw; from expansion of marrow cavity in bones of skull and face
G6PD:
1) What is it? What is the mutation?
2) What is G6PD?
1) Glucose-6-Phosphate Dehydrogenase Deficiency
X-linked recessive mutation in G6PD gene
2) An enzyme that processes glucose, which results in production of NADPH
G6PD: What drugs affect it?
Chlorpropamide – anti-diabetic
Dapsone – antibiotic with anti-inflammatory properties
Fluoroquinolones – “floxacins” antibiotics
Nitrofurantoin – antibiotic
Sulfa drugs
Antimalarial – “quines”
G6PD: What chemicals and foods can affect it?
1) Fava beans
2) Henna
3) Naphthalene (moth balls)
G6PD:
1) When do changes occur?
2) What will a peripheral blood smear show?
1) 3-5 days after exposure
2) RBC with precipitates of denatured globin (Heinz bodies) with splenic macrophages that have “plucked out” these inclusions; “bite cells”
List 4 anemias of diminished erythropoiesis
1) Iron Deficiency Anemia
2) Anemia of Chronic Inflammation
3) Megaloblastic Anemia
4) Aplastic Anemia
1) Most common anemia in hospitalized patients is what? 2) Give 3 examples
1) Anemia of chronic disease
2) Chronic microbial infections; chronic immune disorders; neoplasms
Anemia of Chronic Disease:
1) How is iron involved? What happens to MCV?
2) Can EPO help? Explain
1) Iron is actually being stored so ferritin is high
Therefore, iron is not desired so TIBC is low
The MCV remains normal and the cells are not hypochromic
2) Administration of EPO can improve anemia, but treatment of underlying disease is curative
Megaloblastic: Folate and B12
What are the building blocks of DNA? What does the T stand for?
Nucleotides ACTG; T = thiamine
1) What does T stand for in DNA?
2) What does it come from? What can’t it be produced without?
3) What would happen if it was absent?
1) Thiamine
2) Thiamine comes from Thymidine, which is a precursor of thiamine (combined with a ribose sugar) and is then converted to thiamine
-Thiamine cannot ultimately be produced without folate and B12
-DNA cannot be replicated when these compounds are deficient, and DNA is eventually damaged
3) The body then experiences increased production of large, red blood cell precursor cells, called megaloblasts
Megaloblastic: Folate Deficiency
1) What causes it? Explain & incl. who’s at high risk
2) What are 2 clinical features?
1) Due to inadequate dietary intake
-Folate is ubiquitous, but destroyed by 10-15 minutes of cooking
-When levels fall, DNA cannot be replicated and is damaged > megaloblastic anemia
-High risk for this disease in those with poor nutrition and those with increased metabolic demand (pregnant women)
2) Weakness and fatigue
Folate deficiency megaloblastic anemia can be diagnosed with what 3 things?
MCV, blood smear, folate level
Megaloblastic: B12 Deficiency
1) What is B12 also called?
2) What releases B12 from food?
1) “Cobalamin”
2) Pepsin and other gastric juices
We have enough B12 stored in the liver for 5 years!
Megaloblastic: B12 Deficiency
1) What secretes intrinsic factor? What does it bind?
2) Where does B12 go?
1) Parietal cells in the mucosa of gastric fundus; binds to B12 in the stomach and passes to the distal ilium
2) There it is absorbed into enterocytes; B12 is then transferred to liver and body cells
B12 anemia is accompanied by __________ symptoms
neurologic
Megaloblastic: B12 Deficiency
What are the clinical Fx?
1) Fatigue, malaise
2) Beefy red tongue (late) – megaloblastic changes in oropharyngeal epithelium
3) Spinal cord disease – B12 anemia is accompanied by neurologic symptoms
4) Numbness, tingling or burning in feet or hands
5P) Unsteadiness of gait and diminished proprioception
Megaloblastic: B12 Deficiency
1) Its pathology is intertwined with what? Explain
2) What can improve the anemia? Explain.
1) Folate; in that it affects DNA synthesis and leads to macrocytic anemia
2) May be improved even with the administration of folate, but the neurological symptoms will not, and may even worsen
Aplastic Anemia:
1) What is it? What causes it?
2) What are the Sx?
1) Bone marrow failure and pancytopenia; half of cases are idiopathic, remaining half caused by exposure to myelotoxic agents (e.g., toxins, radiation, hypersensitivity to drugs or viruses)
-Bone marrow hypocellular with fat replacement
-Autoreactive T cells may be the reason for marrow failure
2) Anemia, thrombocytopenia, neutropenia
Slowly progressive, weakness, pallor, dyspnea
Hydrops fetalis, Hb Bart’s (y4):
1) What is it?
2) What does it cause?
1) Infants suffer from severe intrauterine hypoxia and are born with massive generalized fluid accumulation (type of Alpha Thalassemia)
2) Infant death
1) Define aplastic anemia
2) What are half of cases caused by?
3) What causes the other half?
4) What happens to the bone marrow?
5) Is it progressive? Sx?
1) Bone marrow failure and pancytopenia caused by suppression of multipotent myeloid stem cells
2) Idiopathic
3) Exposure to myelotoxic agents (e.g., toxins, radiation, hypersensitivity to drugs or viruses)
4) Bone marrow hypocellular with fat replacement
(Autoreactive T cells may be the reason for marrow failure)
5) Slowly progressive, weakness, pallor, dyspnea; anemia, thrombocytopenia, neutropenia
Differentiate between primary (polycythemia vera) and secondary polycythemia. What causes each?
1) Primary: Clonal proliferation of myeloid stem cells
Uncontrolled production of red blood cells and an increased total red blood cell mass
2) Secondary: Increased red blood cell volume owing to erythroid bone marrow hyperplasia caused by erythropoietin
-Usually caused by prolonged hypoxia (ex: living at high altitudes, anoxia secondary to chronic lung disease, congenital heart disease, renal carcinoma)
Define polycythemia
(Erythrocytosis) is the result of an abnormal increase in red blood cell number
Polycythemia vera:
1) Sx?
2) What is there an increased risk of?
1) Hypertension, dark red or flushed face, headaches, puritis, visual problems, neurologic symptoms, splenomegaly, hypercellular bone marrow
2) Deep vein thrombosis (DVT), heart attack, stroke, leukemia
What are the 2 categories of leukocytic disorders?
Technically benign (often secondary) and malignant
What are two technically benign leukocytic conditions (usually secondary)? What does each mean?
1) Leukopenia: white cell count below normal
2) Leukocytosis: white cell count above normal
List and describe 3 malignant leukocytic disorders
1) Leukemia: arising from white cell precursors in bone marrow, in periphery (acute and chronic)
-Lymphoid + Myeloid stem cells
2) Lymphoma: arising from white cells in lymph nodes (Non-Hodgkin’s and Hodgkin’s)
3) Multiple myeloma: malignant plasma cells arising in bone marrow
Leukopenia
1) Define it
2) When may it be seen? Give examples
1) Reduction in WBC count to below normal
2) Sepsis; neutropenia (potential cause); chemotherapy (decrease in production); increased destruction (drugs, infection, sequestration in the spleen)
Leukocytosis:
1) What often causes it?
2) What else can cause it?
3) When may a slight increase be seen?
1) Inflammatory response
2) Infection; in extremely high numbers, suspect leukemia
3) Slight rise may be seen in catecholamine-induced demargination which is stress-induced
Infectious mononucleosis:
1) Etiology?
2) 2 main Sx?
3) Pathogenesis?
1) Epstein Barr virus
2) Lymphadenitis; splenomegaly
3) Latent infected B cells are activated and proliferate
Host T cell ( atypical CD8+ mononuclear) response controls the proliferation of EBV-infected B cells (and thus the spread of the virus)
Cat-Scratch Disease:
1) What is it? Etiology?
2) Who is it most common in?
3) What does it cause?
1) Self limiting lymphadenitis caused by Bartonella hensale
2) 90% are younger than 18
3) Regional lymphadenopathy (most common axilla and neck)
How do leukemias happen?
Bone marrow is infiltrated with malignant cells:
1) Clonal expansion of neoplastic stem cells with genetic changes specific to each disease
2) Failure of maturation
3) Suppression of normal hematopoiesis
Leukemias:
1) Peripheral blood contains what?
2) What are 3 complications?
1) An increased number of immature blood cells
2) Anemia, recurrent infections, and uncontrollable bleeding
Differentiate myeloblast vs. lymphoblast
1) Myeloblast: Precursor for myelocytes
-can differentiate into granulocytes: Basophils, Eosinophils, etc
2) Lymphoblast: Precursor of lymphocytes
-can differentiate into lymphocytes: B cells, T cells
Hodgkin’s lymphoma:
1) How does it spread?
2) What are the B symptoms? (3)
3) What is another Sx?
4) What cells can be found?
1) Contiguous spread
2) Fever/chills, night sweats, weight loss
3) Nontender LAD
4) Reed Sternberg Cells: Large, abnormal lymphocytes, often with multiple nuclei
Non-hodgkin’s:
1) How does it spread?
2) Are there B Sx?
3) What else differentiates this from Hodgekin’s?
1) Hematogenous Spread
2) Usually no B sx
3) Nontender LAD; NO reed Sternberg cells
Disseminated Intravascular Coagulation(DIC):
1) What is it?
2) What can dominate it?
3) What are some common triggers?
1) Systemic activation of the coagulation leads to consumption of coagulation factors and platelets
2) Bleeding, vascular occlusion and tissue hypoxemia, or both
3) Sepsis, major trauma, certain cancers, obstetric complications
Idiopathic Thrombocytopenic Purpura(ITP):
1) What causes it?
2) What may trigger it?
1) Autoantibodies against platelet antigens
2) Drugs, infections, or lymphomas, or may indeed be idiopathic
Thrombotic Thrombocytopenic Purpura (TTP):
1) What causes it?
2) What does this lead to?
1) Acquired or inherited deficiencies of ADAMTS 13, a mutation that inhibits platelet function through vW factor. Causes large platelet aggregation and micro clots.
2) Over use of platelets and then bleeding.
Hemolytic Uremic Syndrome (HUS):
1) What causes it? Name one factor in particular
2) What does it initiate and what does this lead to?
3) What else does it cause?
1) Deficiencies of complement regulatory proteins; triggered frequently by infection, in particular E Coli
2) Platelet activation platelet aggregation; leads to thrombocytopenia
3) RBC destruction
1) What 3 Sx do Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic Uremic Syndrome (HUS) have in common?
2) What are more typically of TTP?
1) Thrombocytopenia, microangiopathic hemolytic anemia, and renal failure
2) Fever and CNS involvement
von Willebrand Disease:
1) What is it? What is its inheritance?
2) What does it cause?
3) What are the Sx?
1) Autosomal dominant disorder caused by mutations in vWF, a large protein that promotes the adhesion of platelets to subendothelial collagen.
2) Impairment of vWF function = decreased platelet aggregation
3) Typically a mild to moderate bleeding disorder resembling that associated with thrombocytopenia
Hemophilia: what are the 2 types?
A and B
Differentiate between hemophilia and and hemophilia B
1) Hemophilia A: Most common cause of hereditary bleeding.
-X-linked disorder caused by mutations in factor VIII.
-Affected males typically present with severe bleeding into soft tissues and joints have a prolonged PTT.
2) Hemophilia B: X-linked disorder caused by mutations in coagulation factor IX.
-Clinically identical to hemophilia A.
