Heme

Question 1

Variations in normal hemoglobin

Answer 1

Fetal hgb and polycythemia
Hemolytic disease of the new born
Aging (men decrease in testosterone) is not physiologic
Altitude greater than 1000 meters above sea level
Smoking increases carboxyhemoglobin increase in hgb to compensate

Question 2

Removal and byproducts of RBCs

Answer 2

Life span about 120 days
Removed by macrophages (spleen)
Cells decrease ATP-cell membrane becomes more frail and digested by preolytic and lipolytic enzymes in phagolysosomes
Heme and globulin dissociate-iron is recycle as ferritin and globulin becomes amino acid

Question 3

Metabolism of bilirubin

Answer 3

Porphyria reduces to unconjugated bilirubin
Conjugated (water and soluble) excreted by liver, intestine or bile
Bacteria in intestinal linen=conjugated bilirubin to urobilinogen
Excreted in feces
Some is reabsorbed and excreted by the kidneys
Gallstone if chronically elevated bili excretion

Question 4

Oxygen dissociation curve

Answer 4

Right
High pCO2, low affinity for 02, high hydrogen, low pH, high 2-3 DPG, high temp
Left
Low pCO2, low hydrogen, low 2,3 DPG, low temp

Question 5

HbA

Answer 5

Alpha 2 beta 2 92% of adult hgb

Question 6

HbA1c

Answer 6

Alpha 2 (beta Nh glucose) 5% of adult hgb, high in DM

Question 7

HbA2

Answer 7

Alpha 2 beta 2-2% of adult hgb high in beta thalassemia

Question 8

HbF

Answer 8

Alpha 2 Y 2 major fetal hgb from 3rd to 9th month of gestation, promotes o2 transfer across platelets, high in beta thalassemia

Question 9

Hb grower 1,2 and Hb Portland

Answer 9

Present in early embryo, function unknown

Question 10

Trigger of RBC production

Answer 10

Low o2 due to anemia/hypoxia
Decreased blood volume
Poor blood flow
Pulmonary disease
Increased levels of androgens

Question 11

Key components of a hemoglobin molecule

Answer 11

Krebs cycle form succinylco-A
Each molecule has 2 polypeptide chain globulins alpha and beta
4 components of the iron plus protoporphyrin (heme)
Heme synthesized in the mitochondria can carry one molecule of 02 each
Protoporphyrin bound with ferrous iron (binding oxidizes to Fe2+ to oxyhemoglobin) releases 02 deoxyhemoglobin without the reaction Fe 3+ Hb (methoemoglobin) cannot bind to 02
4 components of sets of alpha and beta each can carry one 02 molecule (max 4 molecule per RBC)

Question 12

Hematopoiesis

Answer 12

7 days
Controlled by erythropoietin in the kidneys tissue 02 levels stimulate bone marrow
Flat bones of pelvis, vertebrae, cranium and mandible
Transcription of erythropoietin is mediated by hypoxia induced factor 1
Epo binds to receptors and stimulates erythroid cell division and proliferation and inhibits apoptosis
In infants process starts in the yolk sac then switches to liver at two months after birth goes to marrow
If extra RBC are needed process occurs in liver and spleen

Question 13

Pluripotent

Answer 13

Pluripotential hematopoietic stems cells in the bone marrow differentiate
Committed stem cells turn into colony forming units then blastocysts and immature RBC erythroblasts, reticulocytes and then erythrocytes

Question 14

Anemia

Answer 14

Reduction in total erythrocytes, hgb, hct
Women hgb less than 12
Men hgb less than 13

Question 15

MCV

Answer 15

Mean corpuscular volume aka size

Question 16

MCHC

Answer 16

Mean corpuscular hemoglobin concentration aka amount of hgb in RBC compared to size and color

Question 17

RDW

Answer 17

Red cell distribution width

Question 18

Microcytic anemia

Answer 18

MCV less than 80
If serum iron and ferritin low-iron deficiency anemia
If serum urine normal or elevated, serum ferritin normal or elevated, or TIBC normal, hgb electrophoresis normal is alpha abnormal in beta- thalassemias
Serum iron normal or deceased, serum ferritin normal or elevated, TIBC normal or decreased, hgb electrophoresis is normal-chronic disease

Question 19

Normocytic Anemia

Answer 19

MCV 80-100
Causes acute blood loss, chronic disease, hemolysis, infection, inflammation, malignancy, renal insufficiency, sickle cell

Question 20

Marcocytic anemia

Answer 20

MCV greater than 100
If serum B12 low, hemocysteine elevated, serum folate low
Then test methylmaloic acid
If elevated- vitamin B12 deficiency
If normal- folate deficiency
If serum B 12 and folate are normal causes include alcoholism, bone marrow disease, hypothyroidism, liver disease, medication like chemotherapy and antivirals

Question 21

Iron studies

Answer 21

Iron 70% in hgb/30% stored
Ferritin-acute phase reactant/amount stored of iron
Transferrin-ability of body to transport
Iron brining capacity (TIBC) protein available to bind iron (high in iron deficiency anemia, low in inflammatory or malignancy)

Question 22

Types of anemia

Answer 22

Anemia of chronic illness, hemolytic, aplastic, sickle cell, pernicious, folate deficiency

Question 23

Anemia of chronic illness

Answer 23

Rule out diagnosis
2nd most common
Due to chronic infection, inflammation, chronic disease
Pro inflammatory cytokines, inhibit erythropoietin production. Destroys immature erythroblasts
Stimulates release of hepicidin- control irons absorption in blood and GI tract, blocks release of iron reticuloendothelial system, decreases oral iron absorption leading to deficiency

Question 24

Hemolytic anemia

Answer 24

Destruction of RBCs due to genetics, ABO incompatibility, autoimmune (lupus, RA), drugs (NSAID, cephalosporins) newborns- hyperbilirubinemia,
High bili, high pH, high uric acid, high hemoglubinuria, decreased haptoglobin

Question 25

Aplastic anemia

Answer 25

Usually stem cell disorder Congenital, chemo, viral, autoimmune Bone marrow bx All cells lines down

Question 26

Iron deficiency anemia

Answer 26

Chronic blood loss, diet, malabsorption, pregnancy, increase in children during growth periods

Question 27

Sickle cell

Answer 27

Autosomal recessive-hemolytic Disease or trait 1:500 AA hgb low 02 capacity Exacerbations/crisis-infection, dehydration, hypoxia, vasoocclusion, pain Increased risk for MI, CVA, pulm injury.

Question 28

Pernicious anemia

Answer 28

Low B12 Less effective DNA synthesis and short RBC life Unable to absorb B12 (lack intrinsic factor), dietary, autoimmune Parasthesias, balance, oral pain, increase in homocysteine

Question 29

Folate deficiency anemia

Answer 29

Impaired RNA/DNA synthesis Dietary deficiency, poor absorption, drugs (ASA) maternal deficiency can results in neural tube defects

Question 30

Decreased RBC production, decreased reticulo count, normocytic and normochromatic

Answer 30

Aplastic or anemia of inflammation

Question 31

Decrease RBC, decreased reticulo count, macrocytic, normochromatic, low B 12 level

Answer 31

Pernicious anemia

Question 32

Decrease RBC, decreased reticulo count, microcytic and hypochromatic

Answer 32

Iron deficiency anemia

Question 33

Anemia low hgb low hct normochromatic normocytic

Answer 33

Acute blood loss

Question 34

Thalassemia

Answer 34

Autosomal recessive disorder alpha and beta types, mutation on HBB gene Effect synthesis of hgb A-change in ratio changes the structure of hgb making RBC less stable and more likely to break down Alpha is less severe than beta Risk of iron overload- hemosiderosis

Question 35

Increases RBC increases reticulo abnormal shapes, inherited

Answer 35

Sickle cell, spherocytosis, thalassemia

Question 36

Increases RBC increases reticulo, schistocytea, acquired

Answer 36

Autoimmune hemolytic anemia

Question 37

Agranular leukocytes

Answer 37

-cyte cells Lymphocytes 20-25%, monocytes 5-10% Lifespan: Weeks to months for lymph, monk 10-20 hours in blood, months in tissue Role: lymph-ID and neutralize foreign organisms, develop T and B cells, mono-phagocytosis High lymph count indicates infection and inflammation, low with steroids High Mono count indicates myelodyplasia, Protozoa, rickettsia

Question 38

Granular leukocytes

Answer 38

-Phil cells Neutrophils 60-70%, eosinophils 2-4%, basophils 1%, Seg or polys Life span: in blood 4-8 hours, tissue 4-5 days Role: neutrophils are 1st responders, eosinophils-allergy/parasites, mast cells

Question 39

Leukemia

Answer 39

Leukocytes in BM -/+ Overproduction-crowds marrow can’t produce other cells, other organs are infiltrated with leukocytes (spleen, liver, lymph, CNS) Types: two types: myelodysplastic (acute myeloid leukemia) and lymphoid (Acute lymphoblastic leukemia, chronic lymphocytic leukemia)

Question 40

Acute myloid leukemia

Answer 40

Myelodysplatic type Epigenetic alterations Myeloproliferative neoplasms, chronic myeloid, polycythemia Vera, essential thrombocytopenia

Question 41

Acute lymphoblastic leukemia

Answer 41

Lymphoid type Philadelphia chromosome

Question 42

Chronic lymphocytic leukemia

Answer 42

Lymphoid type Philadelphia chromosome B cells fail to mature needed for humoral immunity increases risk for encapsulated infections

Question 43

Lymphoma

Answer 43

Proliferation of lymphocytes into lymph system Three types: Hodkins, non hodkins, burkitts

Question 44

Hodkins lymphoma

Answer 44

B cell (reed stern berg) common risk factor is EBV Presents as mediastinal node

Question 45

Non Hodkins lymphoma

Answer 45

Heterogenous B cell, T cell and NK cell Common risk factor is hereditary, chemical, EBV, HHV-8, HIV, hep C, transplant suppression Presents as nodes in neck, groin, axilla

Question 46

Burkitts lymphoma

Answer 46

B cells Common risk factor is EBV, peds Presents as jaw, facial, bone and abd node enlargement

Question 47

Myeloma

Answer 47

Clonal plasma cell cancer producing a monoclonal immunoglobulin Proliferation of plasma cells in bone marrow does not allow for production of other cells lines Type multiple myeloma

Question 48

Multiple myeloma

Answer 48

Plasma cell-slow proliferation in bone marrow, increase in IgG, bence jones protein in urine, Lytic bone disease- myeloma cells, hepatic growth/parathyroid hormone, cytokines/osteoclast activation/increase bone reabsorption cause bone lesions and increase in serum Ca Fractures and Renal failure

Question 49

Vascular injury

Answer 49

Results in vasospams, smooth muscle constricts, local humoral response activates substances vessel endothelium, platelets arrive, secrete thromboxane Increase platelets expression/aggregation low dose ASA inhibits

Question 50

Hemostatic platelet plug formation

Answer 50

Occludes small vascular disruptions without activating coag cascade Three steps adhesion, activation and aggregation Platelets adhere to exposed collagen become sticky and adhere to collagen and von wildebrand factor Activation: platelets change shape and form pseudopods and activates archidonic pathway Aggregation: stabilization or platelet plug requires coag factors-thromboxane

Question 51

Clot formation

Answer 51

Coag cascade triggers (15-20 seconds) 1-2 minutes of bleeding is not stopped by plug May be triggered by immune or inflammatory response Platelets aggregation and fibrin thread form true clot in 3-6 minutes 20-60 minute clot retracts to further occlude

Question 52

Extrinsic clotting pathway

Answer 52

Also called tissue factor pathway Release by damaged endothelial cells if the blood vessels and activated factor VII (VIIa) Primary role Measures by PT Leads to common pathway, converge at factor X and thrombin

Question 53

Intrinsic clotting pathway

Answer 53

Also called contact activation pathway Vessel wall damage causes negatively charged endothelial substents to come into contact with hageman factor (XII) Role is to support extrinsic Measures by PTT Leads to common pathway converge at factor X and thrombin

Question 54

Common clotting pathway

Answer 54

Role in both prothrombin activation Measures by factor VII, V, X, PT, fibrinogen Leads to fibrin clot (stops bleeding, prevents spread of inflammation and infection Lee invaders near site of injury initiates formation of 2 fibrinopeptides A&B) chemotatic for neutrophils and increases vacuole permeability, provide a network for healing

Question 55

Clotting system can be activated by

Answer 55

Extrinsic and intrinsic pathways. Both routes lead to activated of factor X and thrombin. Thrombin is on an Wayne that activates fibrinogen do form for in and small FPs. Fibrin comes together to form a clot FPs are highly active chemotatic factors and cause increase in vascular permeability

Question 56

Common sequence of extrinsic and intrinsic pathway

Answer 56

Vascular damage- prothrombin Prothrombin-thrombin Thrombin (enzyme) fibrinogen- fibrin-clot

Question 57

Factor V Leiden

Answer 57

CLOTTING Autosomal dominant Factor Va resists activated protein C lacks breakdown causes excess thrombin

Question 58

Antiphospholipid syndrome

Answer 58

CLOTTING acquired, autoimmune antibodies to plasma proteins and clotting factors Complications in pregnancy

Question 59

Thrombotic thrombocytopenic purpura (TTP)

Answer 59

CLOTTING Generic/autoimmune High amounts of VWF lacks enzymes to breakdown and platelets aggregate Thrombocytopenia Micro vascular thrombi

Question 60

Immune thrombocytopenic purpura

Answer 60

BLEEDING acquired Viral, time limited Platelets phagocytized by macrophages causing too few platelets Presented to CD4 cells IgG antibodies bind to platelets no problem with bone marrow

Question 61

Hemophilia A

Answer 61

BLEEDING Inherited/genetic X linked recessive common deficiency in factor VIII aPTT high.PT normal platelets normal (intrinsic pathway)

Question 62

Hemophilia B

Answer 62

BLEEDING Inherited/genetic X linked recessive deficiency in factor XI aPTT high.PT normal platelets normal (intrinsic pathway)

Question 63

Von wildebrand factor

Answer 63

Helps platelets adhere to one another Too high- TTP Too low- von wildebrand disease

Question 64

Von wildebrand disease

Answer 64

BLEEDING Disorder of clotting factor that results in bleeding Inherited autosomal dominate Low levels of VWF and factor VIII Low levels lead to decreased platelets and adhesion which leads to bleeding

Question 65

DIC

Answer 65

CLOTTING AND BLEEDING widespread clotting may lead to blockage or blood flow to organs and lead to multi organ failure Excess in clotting may consume platelets and clotting factors results in bleeding in setting of widespread clotting Release of procoagulants (tissue factors) wide spread endothelial injury-micro vascular clots-trauma, sepsis, CA Labs Low platelets low clotting factors, high PT, aPTT, d dimer Microvascular clots cause distal tissue injury ischemic tissues

Question 66

Virchows triad

Answer 66

For hyper coagulable disorders Hyper coagulable state Vessel damage Venous stasis

Question 67

Factors related to risk of acquires thrombosis

Answer 67

Arterial or venous Immobile, MI, CA, obesity, estrogen therapy, pregnancy, sickle cell Embolism Prevention Intervention-ASA, heparin, mobilize and decrease stasis

Question 68

Protein essential for clot dissolution

Answer 68

Thrombin and plasminogen activators Thrombin absorbed by fibrin fibers Antithrombin III (AT3) blocks thrombin on fibrinogen inactivating thrombin Heparin with AT 3 increases removal of thrombin 100 fold removed XIIa, XIa, Xa Plasminogen activators- plasmin, clot formation plasminogen trapped, endothelium release tissue plasminogen activator (tpa) converts plasminogen to remove clot after vessel healed, proteolytic enzymes: digest fibrin fibers, fibrinogen, prothrombin, and factors V. VIII, XII

Question 69

Aging and coagulation

Answer 69

Blood clots move easily levels of fibrinogen factor V, VII, IX, VWF, increase platelet activation Less active and chromic inflammation

Question 70

Hemostasis

Answer 70

Prevention of blood loss through vascular spasm, formation of platelet plug and formation of fibrous clot

Question 71

Categorizing leukemias

Answer 71

Acute- blast cells are present or chronic-well differentiated cells Lymphocytic-too many lymphoblastic Or myelogenous- too many myeloblast

Question 72

Inherited coagulopathies

Answer 72

Von wildebrand disease Factor V lidien, protein c deficiency, protein s deficiency

Question 73

Acquired coagulopathies

Answer 73

Uremia Antiphospholioid syndrome, cancer, pregnancy