Lecture 5.1: blood

Question 1

What are the main types of blood disorders?

Answer 1

1) Red Cells
2) White Cells
3) Clotting: Platelets or factors

Question 2

Red cell disease: What are the 3 ways you can have an issue?

Answer 2

1) Loose your RBC’s > bleeding
2) Kill your RBC’s > hemolysis
3) Stop making RBC’s > decreased production

Question 3

What are the two main types of anemia? What can each cause?

Answer 3

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

Question 4

1) The growth factor responsible for making new RBC’s is ________________.
2) List 3 ways to measure iron

Answer 4

1) erythropoietin (EPO) (from kidneys)
2) Iron level, iron binding capacity, ferritin

Question 5

List and describe 3 ways to measure red blood cells

Answer 5

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

Question 6

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?

Answer 6

1) Conjugated and uncongigated bili
-Hemolytic anemia
2) Macrocytic anemia

Question 7

True or false: Hemoglobin is relative

Answer 7

True

Question 8

1) What should you always measure with hemoglobin labs?
2) Why?

Answer 8

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

Question 9

When the onset of anemia is slow (i.e. chronic), what are 2 things that happen? What do these do?

Answer 9

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

Question 10

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?

Answer 10

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)

Question 11

1) Chronic blood loss gradually depletes ____ stores.
2) Why does chronic blood loss lead to chronic anemia of underproduction?

Answer 11

1) iron
2) You can’t make proper Hgb without iron

Question 12

Chronic bleed will demonstrate what 3 things? Why?

Answer 12

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

Question 13

Chronic bleeding:
1) Why is ferritin low?
2) What is an important implication of high ferritin?

Answer 13

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

Question 14

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?

Answer 14

1) 120
2) lysed; unconjugated bilirubin
3) The bili wasn’t able to be conjugated through normal delivery to the liver

Question 15

What does hemolysis lead to? What should you check?

Answer 15

1) Hemolysis > low 02 > increased EPO > increased reticulocytes being made
2) Therefore, check the reticulocyte count; it will be high in this disease

Question 16

What are 2 ways to classify the cause of hemolysis?

Answer 16

Intravascular and extravascular

Question 17

Extravascular hemolysis:
1) What causes it?
2) Where does this often happen, and why does this happen there?

Answer 17

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”

Question 18

Define sequestration

Answer 18

A process by which the spleen traps cells with diminished deformability and feeds them to macrophages

Question 19

List 3 findings in extravascular hemolysis

Answer 19

1) Hyperbilirubinemia and jaundice
2) Late-stage, gallstones and cholelithiasis
3) Sometimes splenomegaly

Question 20

What is the pathway of hemolysis?

Answer 20

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

Question 21

Intravascular hemolysis:
1) What is it? What can cause it?
2) What does this release? Explain

Answer 21

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

Question 22

What two things do both intra and extravascular hemolysis cause?

Answer 22

1) Increased unconjugated bilirubin
2) Decreased haptoglobin

Question 23

What is haptoglobin?

Answer 23

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

Question 24

Hereditary Spherocytosis:
1) What is the inheritance pattern?
2) What does it lead to? What does this cause?

Answer 24

1) Autosomal dominant
2) Intrinsic defect in RBC membrane; spherical, non-deformable cell causes sequestration and destruction in the spleen

Question 25

Hereditary Spherocytosis: 1) What 2 proteins are mutated? What are both? 2) What do these mutations cause? What are the effects of this?

Answer 25

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

Question 26

Hereditary Spherocytosis: 1) What are 3 clinical features? 2) Is there anemia? Describe 3) What is the Tx?

Answer 26

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)

Question 27

Compare HgA to HgF

Answer 27

1) Adult (HgA): Combination of alpha-globin and beta-globin 2) Fetal (HgF): Combination of gamma-globin and alpha-globin

Question 28

HgA and HgF: By _____________ of age gamma-globin is gradually replaced with beta-globin

Answer 28

six months

Question 29

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?

Answer 29

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

Question 30

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?

Answer 30

1) Infarct in bones in said regions 2) Sluggish blood flow to inflamed lung > hypoxia 3) Yes 4) Vasoocclusions in the eye; Proliferative retinopathy

Question 31

Thalassemias: 1) What are they? 2) What do they cause? 3) Can it be lethal? Explain

Answer 31

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

Question 32

Alpha thalassemia 1) What does it cause? 2) What is the most common cause of this condition? 3) How many alleles?

Answer 32

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

Question 33

Beta thalassemia: 1) What does it cause? 2) What is the most common cause of it? 3) How many genes and alleles?

Answer 33

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

Question 34

Alpha Thalassemia: 1) What is it? 2) What happens once 3 or more alpha-globin chains are lost? 3) What does this lead to?

Answer 34

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

Question 35

Alpha Thalassemia: Infants will build up tetramers of gamma-globin until when?

Answer 35

6 months of age

Question 36

Both tetramers involved in alpha thalassemia have high affinity for oxygen, so what does this cause?

Answer 36

They won’t let it go

Question 37

Hb H (B4) disease: 1) What is it? 2) Why does it develop?

Answer 37

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.

Question 38

A child with untreated B-thalassemia major may look like what? Why?

Answer 38

Prominent cheekbones and protrusion of upper jaw; from expansion of marrow cavity in bones of skull and face

Question 39

G6PD: 1) What is it? What is the mutation? 2) What is G6PD?

Answer 39

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

Question 40

G6PD: What drugs affect it?

Answer 40

Chlorpropamide – anti-diabetic Dapsone – antibiotic with anti-inflammatory properties Fluoroquinolones – “floxacins” antibiotics Nitrofurantoin – antibiotic Sulfa drugs Antimalarial – “quines”

Question 41

G6PD: What chemicals and foods can affect it?

Answer 41

1) Fava beans 2) Henna 3) Naphthalene (moth balls)

Question 42

G6PD: 1) When do changes occur? 2) What will a peripheral blood smear show?

Answer 42

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”

Question 43

List 4 anemias of diminished erythropoiesis

Answer 43

1) Iron Deficiency Anemia 2) Anemia of Chronic Inflammation 3) Megaloblastic Anemia 4) Aplastic Anemia

Question 44

1) Most common anemia in hospitalized patients is what? 2) Give 3 examples

Answer 44

1) Anemia of chronic disease 2) Chronic microbial infections; chronic immune disorders; neoplasms

Question 45

Anemia of Chronic Disease: 1) How is iron involved? What happens to MCV? 2) Can EPO help? Explain

Answer 45

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

Question 46

Megaloblastic: Folate and B12 What are the building blocks of DNA? What does the T stand for?

Answer 46

Nucleotides ACTG; T = thiamine

Question 47

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?

Answer 47

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

Question 48

Megaloblastic: Folate Deficiency 1) What causes it? Explain & incl. who's at high risk 2) What are 2 clinical features?

Answer 48

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

Question 49

Folate deficiency megaloblastic anemia can be diagnosed with what 3 things?

Answer 49

MCV, blood smear, folate level

Question 50

Megaloblastic: B12 Deficiency 1) What is B12 also called? 2) What releases B12 from food?

Answer 50

1) “Cobalamin” 2) Pepsin and other gastric juices We have enough B12 stored in the liver for 5 years!

Question 51

Megaloblastic: B12 Deficiency 1) What secretes intrinsic factor? What does it bind? 2) Where does B12 go?

Answer 51

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

Question 52

B12 anemia is accompanied by __________ symptoms

Answer 52

neurologic

Question 53

Megaloblastic: B12 Deficiency What are the clinical Fx?

Answer 53

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

Question 54

Megaloblastic: B12 Deficiency 1) Its pathology is intertwined with what? Explain 2) What can improve the anemia? Explain.

Answer 54

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

Question 55

Aplastic Anemia: 1) What is it? What causes it? 2) What are the Sx?

Answer 55

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

Question 56

Hydrops fetalis, Hb Bart’s (y4): 1) What is it? 2) What does it cause?

Answer 56

1) Infants suffer from severe intrauterine hypoxia and are born with massive generalized fluid accumulation (type of Alpha Thalassemia) 2) Infant death

Question 57

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?

Answer 57

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

Question 58

Differentiate between primary (polycythemia vera) and secondary polycythemia. What causes each?

Answer 58

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)

Question 59

Define polycythemia

Answer 59

(Erythrocytosis) is the result of an abnormal increase in red blood cell number

Question 60

Polycythemia vera: 1) Sx? 2) What is there an increased risk of?

Answer 60

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

Question 61

What are the 2 categories of leukocytic disorders?

Answer 61

Technically benign (often secondary) and malignant

Question 62

What are two technically benign leukocytic conditions (usually secondary)? What does each mean?

Answer 62

1) Leukopenia: white cell count below normal 2) Leukocytosis: white cell count above normal

Question 63

List and describe 3 malignant leukocytic disorders

Answer 63

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

Question 64

Leukopenia 1) Define it 2) When may it be seen? Give examples

Answer 64

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)

Question 65

Leukocytosis: 1) What often causes it? 2) What else can cause it? 3) When may a slight increase be seen?

Answer 65

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

Question 66

Infectious mononucleosis: 1) Etiology? 2) 2 main Sx? 3) Pathogenesis?

Answer 66

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)

Question 67

Cat-Scratch Disease: 1) What is it? Etiology? 2) Who is it most common in? 3) What does it cause?

Answer 67

1) Self limiting lymphadenitis caused by Bartonella hensale 2) 90% are younger than 18 3) Regional lymphadenopathy (most common axilla and neck)

Question 68

How do leukemias happen?

Answer 68

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

Question 69

Leukemias: 1) Peripheral blood contains what? 2) What are 3 complications?

Answer 69

1) An increased number of immature blood cells 2) Anemia, recurrent infections, and uncontrollable bleeding

Question 70

Differentiate myeloblast vs. lymphoblast

Answer 70

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

Question 71

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?

Answer 71

1) Contiguous spread 2) Fever/chills, night sweats, weight loss 3) Nontender LAD 4) Reed Sternberg Cells: Large, abnormal lymphocytes, often with multiple nuclei

Question 72

Non-hodgkin’s: 1) How does it spread? 2) Are there B Sx? 3) What else differentiates this from Hodgekin's?

Answer 72

1) Hematogenous Spread 2) Usually no B sx 3) Nontender LAD; NO reed Sternberg cells

Question 73

Disseminated Intravascular Coagulation(DIC): 1) What is it? 2) What can dominate it? 3) What are some common triggers?

Answer 73

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

Question 74

Idiopathic Thrombocytopenic Purpura(ITP): 1) What causes it? 2) What may trigger it?

Answer 74

1) Autoantibodies against platelet antigens 2) Drugs, infections, or lymphomas, or may indeed be idiopathic

Question 75

Thrombotic Thrombocytopenic Purpura (TTP): 1) What causes it? 2) What does this lead to?

Answer 75

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.

Question 76

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?

Answer 76

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

Question 77

1) What 3 Sx do Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic Uremic Syndrome (HUS) have in common? 2) What are more typically of TTP?

Answer 77

1) Thrombocytopenia, microangiopathic hemolytic anemia, and renal failure 2) Fever and CNS involvement

Question 78

von Willebrand Disease: 1) What is it? What is its inheritance? 2) What does it cause? 3) What are the Sx?

Answer 78

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

Question 79

Hemophilia: what are the 2 types?

Answer 79

A and B

Question 80

Differentiate between hemophilia and and hemophilia B

Answer 80

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.