Heme Flashcards
Erythrocytes Microscopic Anatomy
small and biconcave
do not contain mitochondria or a nucleus
hemoglobin: four globin proteins and iron
Cl/HCO3 antiporter
Erythrocytes Origins
bone marrow
Erythrocytes` Maturation
in blood
Erythrocytes function
oxygen transport
transport of carbon dioxide
Erythrocytes` regulation
erythropoietin
low oxygen levels, increased levels of androgens
need iron, copper, zinc, folate, and B12
Erythrocytes synthesis
EPO -> bone marrow and iron is released from storage to red marrow -> stem cell -> erythroblast -> reticulocyte -> RBC
Erythrocytes degradation
120 days broken down in liver and spleen
globin -> amino acids
heme -> biliverdin -> bilirubin
iron -> bound to transferrin -> ferritin
Thrombocytes Microscopic Anatomy
anucleate, roughly disc-shaped small cytoplasmic fragments
dense granules: CASH Ca, ADP, Serotonin, Histamine
alpha granules:
Thrombocytes Origins
bone marrow
Thrombocytes Maturation
bone marrow
Thrombocytes function
platelet plug
Thrombocytes regulation
thrombopoietin from kidney
Thrombocytes synthesis
thrombopoietin from kidney -> myeloid stem cells -> megakaryoblast -> megakaryocytes -> platelets
Thrombocytes degradation
8-10 phagocytized by macrophages
Neutrophil Microscopic Anatomy
segmented nuclei
leukocyte alkaline phosphatase, collagenase, lysozyme, lactoferrin, proteinase, acid phosphatase, myeloperoxidase, beta-glucuronidase
Basophil Origins
bone marrow
Neutrophil Maturation
mature in bone marrow and release into blood 2 days after maturation
Neutrophil function
phagocytosis
Neutrophil regulation
presence of bacteria
colony -stimulating factors
Neutrophil synthesis
colony -stimulating factors bind multipotent stem cell -> myeloid stem cell -> band -> neutrophil
Eosinophil Microscopic Anatomy
2 lobed nucelli w/ red granules
antihistamine, peroxidase, major basic protein, eosinophil cationic protein, eosinophil-derived neurotoxin
Eosinophil Origins
myeloid stem cell
bone marrow
Eosinophil Maturation
bone marrow
Neutrophil degradation
circulate for 6-10 h move into tissue 2-6 days and then apoptosis by macrophages
Eosinophil regulation
T cell
colony -stimulating factors
Eosinophil synthesis
colony -stimulating factors bind to stem cell -> myeloid stem cell -> eosinophil-basophil progenitor -> myeloblast -> eosinophil
Eosinophil degradation
6 days
Monocyte Origins
myeloid stem cells
Monocyte Maturation
bone marrow
Monocyte function
phagocytize
attract other leukocytes
Basophil Maturation
blood
T lymphocyte function
attack foreign or diseased cells
Basophil regulation
IgE, IL-13, IL-4
colony -stimulating factors
Basophil synthesis
colony -stimulating factors bind to stem cell -> myeloid progenitor -> eosinophil-basophil progenitor -> myeloblast -> basophil
NK function
capable of recognizing cells that do not express “self” proteins on their plasma membrane
Monocyte Origins
myeloid stem cells
bone marrow
Monocyte Maturation
blood
Monocyte function
turns to macrophage
phagocytize
attract other leukocytes
Monocyte regulation
IL-3, stem cell factor, granulocyte-macrophage colony-stimulating factor, and macrophage colony-stimulating factor
Monocyte synthesis
colony -stimulating factors to stem cell -> myeloid -> granulocyte-monocyte progenitor -> monoblast -> promonocyte -> monocyte -> macrophage
Monocyte degradation
months
T lymphocyte Microscopic Anatomy
one large nucleus
receptors on membrane
T lymphocyte Origins
bone marrow
T lymphocyte function
CD8: kill target cells
CD4: activating other immune cells, releasing cytokines, and helping B cells to produce antibodies.
T lymphocyte regulation
infection or foreign substance
T lymphocyte synthesis
stem cell -> lymphoid progenitor -> small lymphocyte -> T lymphocyte
B lymphocytes Microscopic Anatomy
large nucleus
B lymphocytes Microscopic Anatomy
large nucleus
receptors on membrane
B lymphocytes function
produce antibodies, antigen-presenting cells, supporting other mononuclear cells
B lymphocytes synthesis
hematopoietic stem cell -> pro-B cell -> pre B cell -> immature B cell -> transitional/regulatory b cell -> naive be cell
NK Microscopic Anatomy
large, granular, perforin and granzyme
NK Origins
lymphoid stem cells
bone
NK function
capable of recognizing cells that do not express “self” proteins on their plasma membrane,
NK regulation
IL-12
NK synthesis
Hematopoietic stem cell -> lymphoid progenitor -> NK
Hematopoiesis
reg: interleukins, colony -stimulating factors, erythropoietin, thrombopoietin
Hematopoiesis
reg: interleukins, colony -stimulating factors, erythropoietin, thrombopoietin
Formation of WBC and RBC
Hemostasis
- nerve in surrounding area detect the injury and reflexive contraction/vasoconstriction
- endothelin is secreted by endothelial cells which causes smooth muscle to constrict
- damage endothelium releases von Willebrand’s Factor that binds to exposed collagen
- platelets circulating bind to the VWF via GP1B receptor
- platelet changes shape, releases vWF, serotonin, and Ca, ADP, thromboxane A2
- this attracts more platelets and activate other platelets that haven’t bound to vWF, ADP and thromboxane A2 bind to platelets and activate them
- platelets can bind to collagen, platelets can bind fibrinogen via GPIIB/IIIA linking two platelets together
8.
Hemostasis Primary
- nerve in surrounding area detect the injury and reflexive contraction/vasoconstriction
- endothelin is secreted by endothelial cells which causes smooth muscle to constrict
- damage endothelium releases von Willebrand’s Factor that binds to exposed collagen
- platelets circulating bind to the VWF via GP1B receptor
- platelet changes shape, releases vWF, serotonin, and Ca, ADP, thromboxane A2
- this attracts more platelets and activate other platelets that haven’t bound to vWF, ADP and thromboxane A2 bind to platelets and activate them
- platelets can bind to collagen, platelets can bind fibrinogen via GPIIB/IIIA linking two platelets together
Secondary Hemostasis
- trauma Factor III in the smooth muscle binds active factor VII w/ Ca forming a VIIa-TF complex on membrane
- cleaves factor X to Xa
- cleaves factor 5 to 5a then binds together which activates Factor II to Factor IIa uses Ca as cofactor
- IIa activates platelets, factor 5, factor 8, and IX, cleaves factor I to Ia, activates XIII to XIIIa
- fibrin forms long protein chains holding platelets together
- XIIIa forms cross links bw fibrin chains
- XII + phosphate cleaves into XIIa
- XIIa cleaves factor XI into XIa + Ca cleaves IX
- IXa binds to VIIIa cleaving X into Xa
Iron Deficiency Anemia def
decrease in healthy RBC due to deficiency in iron
Iron Deficiency Anemia cause
Chronic bleeding (cancer, menses, h pylori, hookworms, etc) Malnutrition Absorption disorders Gastrectomy/surgery Pregnancy, childhood
Iron Deficiency Anemia path
↓ iron -> impaired hemoglobin production -> bone marrow pumps out small and pale RBC -> ↓ O2 to tissue -> ↑ BM activation -> ↑ poikilocytosis (shape) and anisocytosis (size) -> defective mitochondrial enzymes
Iron Deficiency Anemia comp
Plummer-Vinson syndrome (triad of IDA, esophageal webs, dysphagia)
Iron Deficiency Anemia comp
Plummer-Vinson syndrome (triad of IDA, esophageal webs, dysphagia)
Glossitis
esophageal webs
Iron Deficiency Anemia clinical
Fatigue, conjunctival pallor, palpitation, pica, spoon nails (koilonychia), SOB, hair loss
a-Thalassemia def
genetic disorder decadency in alpha chains in hemoglobin
a-Thalassemia cause
a-globin gene deletions on chromo 16, decreased a-globin synthesis
a-Thalassemia cause
a-globin gene deletions on chromo 16, decreased a-globin synthesis
autosomal recessive
a-Thalassemia path
Cis or trans deletion on chromosome that results in absent/reduced alpha globin chains 1 gene carrier 2 genes mild anemia 3 genes hemoglobin H 4 genes incompatible for life
a-Thalassemia RF
Cis deletion - Asian populations
Trans deletion - African populations
areas of high incidence of malaria
a-Thalassemia comp
chronic tissue hypoxia, leg ulcers, high output heart failure, hypermetabolic state, gallstones, bone marrow hyperplasia, bone marrow widens structural malformations, iron deposition in liver, myocardium, pancreas, and kidney
Lead Poisoning-Related Anemia cause
lead exposure
Lead Poisoning-Related Anemia def
anemia due to lead poisoning
Lead Poisoning-Related Anemia RF
contaminated water, lead paint, industrial emissions (smelters, refiners, battery manufacturing, recycling) , lead-glazed ceramics
Lead Poisoning-Related Anemia comp
developmental delays, learning difficulties, chronic kidney disease, HTN, low libido, infertility, SIADH,
Lead Poisoning-Related Anemia clinical
fatigue, dyspnea, activity intolerance, abdominal pain, headache, difficulty concentrating, muscle/joint pain, confusion, ataxia
Beta Thalassemia def
deficiency or absence in the beta chains
Lead Poisoning-Related Anemia clinical
fatigue, dyspnea, activity intolerance, abdominal pain, headache, difficulty concentrating, muscle/joint pain, confusion, ataxia
Beta Thalassemia cause
mutation in beta globins
1: carrier
2: mild anemia
Beta Thalassemia path
genetic mutation -> absent/lack beta chains -> unstable hemoglobin
Beta Thalassemia comp
chronic tissue hypoxia, leg ulcers, high output heart failure, hypermetabolic state, gallstones, bone marrow hyperplasia, bone marrow widens structural malformations, iron deposition in liver, myocardium, pancreas, and kidney
Beta Thalassemia RF
FH, Mediterranean, middle eastern, southeast Asian, African genetic descent
Autoimmune Hemolytic Anemia def
low levels of RBC due to destruction of them
Autoimmune Hemolytic Anemia cause
autoantibodies against antigens on RBCs surface at or below body temp
Autoimmune Hemolytic Anemia path
Warm: IgG to Rh on RBC at normal body temp, antibody fixes complement + binds to RBC membrane -> antibody-coated RBCs destroyed extravascular by macrophages in spleen, liver
Cold: IgM, I, i, P
antibodies activate direct complement system attack, intravascular, complement-mediated
Autoimmune Hemolytic Anemia RF
immune deficiencies, malignancies, certain drugs, measles, varicella, mycoplasma, H. influenza, lymphoproliferative disorders, autoimmune disorders,
Autoimmune Hemolytic Anemia RF
immune deficiencies, malignancies, certain drugs, measles, varicella, mycoplasma, H. influenza, lymphoproliferative disorders, autoimmune disorders, exposure to cold
Autoimmune Hemolytic Anemia comp
venous thromboembolism, cholelithiasis, renal insufficiency, cardiac comp (older)
Autoimmune Hemolytic Anemia clinical
pallor, fatigue, activity intolerance, bounding pulses, tachycardia, pulmonary congestion,
cold: hemoglobinuria, jaundice, pain in legs and back, anemia, acrocyanosis, Raynaud’s, anemia after infx
Autoimmune Hemolytic Anemia clinical
pallor, fatigue, activity intolerance, bounding pulses, tachycardia, pulmonary congestion,
cold: hemoglobinuria, jaundice, pain in legs and back, anemia, acrocyanosis, Raynaud’s, anemia after infx
Glucose-6-Phosphate Dehydrogenase Deficiency cause
inherited, X-linked of G6PD
Glucose-6-Phosphate Dehydrogenase Deficiency path
inadequate G6PD, GSH -> oxidative stress -> build-up of free radicals, peroxides -> precipitation of hemoglobin -> disruption of cell membrane -> ↑ cellular rigidity -> extravascular hemolysis, accelerated removal of damaged RBCs by reticuloendothelial system in spleen; intravascular hemolysis may also occur
Glucose-6-Phosphate Dehydrogenase Deficiency path
inadequate G6PD, GSH -> oxidative stress -> build-up of free radicals, peroxides -> precipitation of hemoglobin -> disruption of cell membrane -> ↑ cellular rigidity -> extravascular hemolysis, accelerated removal of damaged RBCs by reticuloendothelial system in spleen; intravascular hemolysis may also occur
Glucose-6-Phosphate Dehydrogenase Deficiency comp
favism
Glucose-6-Phosphate Dehydrogenase Deficiency clinical
pallor, jaundice, dark urine, abdominal/back pain, renal insufficiency,
Hemolytic Disease of the Newborn def
anemia of the newborn from destruction of RBCs
Hemolytic Disease of the Newborn cause
Rh, A, B, AB, O blood groups
Hemolytic Disease of the Newborn path
fetomaternal hemorrhage exposes maternal circulation to antigens present on fetal RBCs -> maternal sensitization -> formation of maternal IgG antibodies against fetal RBCs -> IgG antibodies small enough to cross placenta -> antibody attachment to fetal cells -> agglutination -> microcirculatory impairment -> hemolysis, destruction of RBCs by macrophages in reticuloendothelial system
Hemolytic Disease of the Newborn RF
blood group incompatibility, fetomaternal hemorrhage
Hemolytic Disease of the Newborn comp
anemia, hyperbilirubinemia, kernicterus, growth restriction, hydrops fetalis, erythroblastosis fetalis
Hemolytic Disease of the Newborn clinical
ABO: hyperbilirubinemia, anemia
Rh: hyperbilirubinemia, kernicterus, pallor, lethargy, tachycardia, tachypnea, subcutaneous edema, pleural/pericardial effusion, ascites, shock
Hereditary Spherocytosis def
RBC membrane defect
Hereditary Spherocytosis cause
autosomal dominant
autosomal recessive
Hereditary Spherocytosis path
mutation of genes encoding for proteins that secure RBC membrane skeleton to plasma membrane -> membrane destabilization -> rigidity, resistance to deformability -> hemolysis
Hereditary Spherocytosis comp
transient aplastic crisis caused by parvovirus B19
megaloblastic anemia
neonatal icterus, non-immune hydrops fetalis
Hereditary Spherocytosis clinical
Mild: anemia, splenomegaly, jaundice, modest reticulocytosis, normal hemoglobin, adolescents/adults
Moderate: anemia, reticulocytosis, hyperbilirubinemia, infants/children
Severe: anemia, hyperbilirubinemia, splenomegaly,
Hereditary Spherocytosis RF
northern European descent
Paroxysmal Nocturnal Hemoglobinuria def
hematologic stem cell disorder
Paroxysmal Nocturnal Hemoglobinuria cause
X-linked, PIGA mutation,
Paroxysmal Nocturnal Hemoglobinuria path
PIGA gene mutated -> ↓ glycosylphosphatidylinositol -> ↑ susceptibility to complement activity -> complement-mediated intravascular hemolysis
Paroxysmal Nocturnal Hemoglobinuria path
PIGA gene mutated -> ↓ glycosylphosphatidylinositol -> ↑ susceptibility to complement activity -> complement-mediated intravascular hemolysis
Paroxysmal Nocturnal Hemoglobinuria comp
smooth muscle dystonia, vasospasm, abdominal pain, esophageal spasm, erectile dysfunction, venous or arterial thrombosis, chronic kidney disease, BM failure, neisserial infx
Paroxysmal Nocturnal Hemoglobinuria clinical
dark urine, hemolysis, pallor, fatigue, exertional dyspnea
Pyruvate Kinase Deficiency def
deficient pyruvate kinase
Pyruvate Kinase Deficiency cause
autosom
Pyruvate Kinase Deficiency cause
autosomal recessive mutation of pyruvate kinase-LR
Pyruvate Kinase Deficiency path
pyruvate kinase deficiency-related block in glycolysis -> accumulation of 2,3-bisophospglucerate -> shifts oxyhemoglobin dissociation curve to right -> improved oxygen delivery to tissues -> better tolerance of hemolytic anemia -> ATP deficiency, apoptosis of erythroid progenitors in spleen
Pyruvate Kinase Deficiency RF
white people of Northern European descent, Asian people of Chinese descent, genetically-isolated communities of Swiss/German descent
Pyruvate Kinase Deficiency comp
pigmented gallstone formation, iron overload-associated organ damage, megaloblastic anemia related to folate deficiency, neonatal icterus/non-immune hydrops fetalis, transient aplastic crisis induced by parvovirus B19
Pyruvate Kinase Deficiency clinical
pallor, SOB, activity intolerance, jaundice, splenomegaly,
Sickle cell anemia def
hemolytic anemia caused by mutation of beta globin
Sickle cell anemia cause
mutation of beta globin
HbSS: homozygous for HbS
HbSC: heterozygous for HbS + abnormal hemoglobin C
HbSA: heterozygous HbS + hemoglobin A
HbS beta thalassemia: heterozygous HbS + 1 beta thalassemia gene
Sickle cell anemia path
point mutation of beta globin gene -> produces hemoglobin S -> RBC polymerize, deform into sickle/crescent-shaped forms when deoxygenated
Sickle cell anemia RF
areas where there are mosquitoes that carry malaria
Sickle cell anemia comp
ischemia/infraction, stroke, transient ischemic attack, seizures, MI, dysrhythmias, cardiomyopathy, HF, thromboembolism, leg ulcers, sudden death, acute chest syndrome, pulmonary HTN, priapism, pregnancy complications, osteoporosis, proliferative retinopathy, retinal detachment, multiorgan failure
Sickle cell anemia clinical
fatigue, activity intolerance, exertional dyspnea, hypersplenism, pain, vaso-occlusion, dactylitis, increased risk of infx,
Hemolytic normocytic anemia
hemolytic disease of newborn, G6PD, autoimmune hemolytic anemia, hereditary spherocytosis, paroxysmal nocturnal hemoglobinuria, pyruvate kinase deficiency, sickle cell anemia,
Macrocytic anemia
megaloblastic anemia, sideroblastic anemia,
Microcytic Hypochromic anemia
iron deficiency, lead poisoning, thalassemia, sideroblastic anemia, late chronic disease anemia
Iron deficiency lab findings
low serum iron low ferritin high iron binding capacity hypochromic microcytic
Lead poisoning lab findings
low serum iron low ferritin high iron binding capacity hypochromic microcytic
Thalassemia lab findings
normal or high iron normal or high ferritin normal iron binding capacity hypochromic microcytic
normocytic normochromic anemia
anemia of chronic disease, aplastic anemia, Autoimmune Hemolytic Anemia, paroxysmal nocturnal hemoglobinuria, fanconi anemia
Anemia of chronic disease def
deficient RBC production due to chronic disease
Anemia of chronic disease cause
infx, cancer, diabetes, autoimmune,
Anemia of chronic disease path
systemic inflammation -> ↑ circulation cytokines, IL-1, IL-6, TNF alpha, IFN beta, IFN gamma -> ↑ hepcidin secretion by liver -> ↓ iron absorption from GI tract, ↓ iron sequestration in reticuloendothelial system -> ↓ iron available for erythropoiesis -> ↓ secretion erythropoietin -> ↓ erythrocyte lifespan
Anemia of chronic disease labs
normochromic normocytic
low serum iron
high ferritin
Anemia of chronic disease labs
normochromic normocytic
low serum iron
high ferritin
low serum transferrin saturation
Aplastic anemia def
bone marrow hypoplasia/aplasia
Aplastic anemia cause
Fanconi anemia, Shwachman-Diamond syndrome, SLE, graft-versus-host disease, paroxysmal nocturnal hemoglobinuria, chemotherapy, carbamazepine, phenytoin, indomethacin, sulfonamides, Epstein-Barr, HIV, hepatitis, herpes, solvents, benzene, pesticides, radiation, idiopathic
Aplastic anemia comp
impaired blood immunity, hemostasis, oxygen-carrying capacities
Aplastic anemia path
bone marrow hypoplasia/aplasia, hematopoietic cell loss -> ↓ production of cell lineages -> peripheral pancytopenia
Aplastic anemia clinical
shorter lifespan, ↑ infx, neutropenia-related sepsis, gingival nares, ecchymosis, petechiae, heavy menstrual flow, occult blood in stool, intracranial hemorrhage, pallor, fatigue, dyspnea, activity intolerance, cardiorespiratory compromise
Aplastic anemia clinical
shorter lifespan, ↑ infx, neutropenia-related sepsis, gingival nares, ecchymosis, petechiae, heavy menstrual flow, occult blood in stool, intracranial hemorrhage, pallor, fatigue, dyspnea, activity intolerance, cardiorespiratory compromise
Diamond-Black Anemia def
inherited bone marrow failure syndrome
Diamond-Black Anemia cause
autosomal dominant
Diamond-Black Anemia path
genetic mutation -> ribosomopathy -> impaired hematopoiesis -> RBC aplasia -> macrocytic normochromic anemia
Diamond-Black Anemia RF
FH
Diamond-Black Anemia comp
myelogenous leukemia, myelodysplastic syndrome, solid tumors
Diamond-Black Anemia clinical
anemia at birth, pallor, tachycardia, apnea, lethargy, low birth weight, low-set ears, micrognathia, high-arched/cleft palate, broad nasal bridge, short neck, congenital glaucoma, cataracts, strabismus, duplex/bifid, flat thenar eminence, horseshoe or absent kidney, ventricular/atrial septal defect, coarctation of aorta,
Diamond-Black Anemia clinical
anemia at birth, pallor, tachycardia, apnea, lethargy, low birth weight, low-set ears, micrognathia, high-arched/cleft palate, broad nasal bridge, short neck, congenital glaucoma, cataracts, strabismus, duplex/bifid, flat thenar eminence, horseshoe or absent kidney, ventricular/atrial septal defect, coarctation of aorta,
Fanconi anemia def
inherited bone marrow failure syndrome
Fanconi anemia cause
mutation of several genes responsible for DNA repair
VACTERL-H
Fanconi anemia path
impaired cellular repair of DNA cross-links -> impaired regulation of cell cycle, genomic instability -> hematopoietic stem cell loss -> macrocytic-normochromic anemia -> bone marrow aplasia -> pancytopenia
Fanconi anemia comp
blood and solid tumor malignancies, life-threatening infx, bleeding tendencies, hypothalamic-pituitary axis disruption, congenital anomalies
Fanconi anemia clinical
increased bruising, bleeding, frequent infx, pallor, SOB, exercise intolerance, microcephaly, congenital heart disease, imperforate anus, conductive deafness, hypogenitalia, café-au-lait spots
Fanconi anemia labs
macrocytic normochromic anemia, pancytopenia
Megaloblastic anemia def
anemia characterized by formation of large RBCs
Megaloblastic anemia cause
cobalamin and/or folate deficiency due to diet, malabsorption, medications, surgery, pancreatic insufficiency, alcoholism
Megaloblastic anemia path
impaired DNA synthesis during erythropoiesis -> uncoordinated maturation of cytoplasm and nuclei in erythroblasts -> abnormally large RBCs + deflective cells w/ fragile membranes -> RBC die prematurely -> anemia
Megaloblastic anemia path
impaired DNA synthesis during erythropoiesis -> uncoordinated maturation of cytoplasm and nuclei in erythroblasts -> abnormally large RBCs + deflective cells w/ fragile membranes -> RBC die prematurely -> anemia
Megaloblastic anemia RF
alcohol use, old age, strict diets,
Megaloblastic anemia clinical
fatigue, activity intolerance, pallor, tachycardia, bounding pulse, jaundice, splenomegaly, glossitis
Folate deficiency def
lack of folate
Folate deficiency cause
malnutrition, malabsorption, drugs (methotrexate, trimethoprim, phenytoin, pregnancy
Folate deficiency path
impaired DNA synthesis during erythropoiesis -> uncoordinated maturation of cytoplasm and nuclei in erythroblasts -> abnormally large RBCs + deflective cells w/ fragile membranes -> RBC die prematurely -> anemia
Folate deficiency RF
alcohol use, strict diets
Folate deficiency clinical
fatigue, activity intolerance, pallor, tachycardia, bounding pulse, jaundice, splenomegaly,
B12 deficiency def
lack of B12 in body
B12 deficiency cause
diet, malabsorption, intrinsic factor deficiency, gastrectomy, pancreatic insufficiency, biguanides, H2 receptor blockers, PPIs, neomycin, Diphyllobothrium latum
B12 deficiency path
impaired DNA synthesis during erythropoiesis -> uncoordinated maturation of cytoplasm and nuclei in erythroblasts -> abnormally large RBCs + deflective cells w/ fragile membranes -> RBC die prematurely -> anemia
B12 deficiency RF
diet, autoimmune, stomach
B12 deficiency comp
infertility, stomach cancer,, neural tube defect
B12 SINs
B12 deficiency clinical
reversible dementia, numbness, tingling, weakness
Folate deficiency comp
infertility, CVD, cancer, neural tube defects
What are the macrocytic hyperchromic anemias?
megaloblastic anemia, Vit B12, folate,
Which anemias is macrocytic normochromic?
Fanconi anemia
Diamond-Black Anemia
Which anemia is microcytic or macrocytic hypochromic?
sideroblastic anemia
sideroblastic anemia def
anemia caused by altered mitochondrial function and defects in heme synthesis w/in erythroid cells
sideroblastic anemia cause
X-linked/autosomal recessive/mitochondrial inheritance, myelodysplastic syndromes, myeloproliferative neoplasms, excessive alcohol, isoniazid, chloramphenicol, copper deficiency, zinc overload
sideroblastic anemia path
impaired erythropoiesis, hemoglobin synthesis -> reduced iron in RBCs + defective RBCs undergo apoptosis w/in bone marrow + fewer functional RBCs in circulation -> anemia
sideroblastic anemia RF
genetics, alcohol, diet
sideroblastic anemia comp
iron overload, hemochromatosis, erythroid hyperplasia of bone marrow, increased risk of infx, acute leukemia, infx fatal
sideroblastic anemia clinical
fatigue, dyspnea, palpitations, pallor, mild jaundice, hepatosplenomegaly, cardiac arrhythmias, HF
Which anemia is Microcytic hyperchromic
hereditary spherocytosis
Polycythemia Vera def
increased blood cells levels due to overproduction by bone marrow
Polycythemia Vera cause
JAK2V617F mutation
Polycythemia Vera path
hematopoietic stem cell -> ↑ RBCs, platelets, basophils, eosinophils -> ↑ blood viscosity, ↑ total blood volume -> may evolve into spent phase
Polycythemia Vera RF
age, genetics
Polycythemia Vera comp
HTN, Budd-Chiari syndrome, DVT, arterial thrombosis, MI, gout, AML
Polycythemia Vera clinical
headache, fatigue, dizziness, dyspnea, plethora, cyanosis, pruritus, gastric ulcers, DVT, MI, portal vein thrombosis, hyperemic and inflamed extremities, bleeding gums, epistaxis, ecchymoses, GI bleed, hepatosplenomegaly, HTN
Polycythemia secondary def
overproduction of RBCS
Polycythemia secondary cause
Chronic lung disease, CHF, Carbon monoxide poisoning, obstructive sleep apnea, renal artery stenosis, tumors, drugs, adrenal cortical hypersecretion
Polycythemia secondary path
↓ oxygen to tissue -> ↑ EPO -> ↑ RBCs
Polycythemia secondary RF
genetics, meds, smoking,
Polycythemia secondary comp
stroke, venous thromboembolism, pulmonary HTN, Increased whole blood viscosity,
Polycythemia secondary clinical
fatigue, headache, and dizziness
Disseminated Intravascular Coagulation def
process of hemostasis gets out of control leading to overproduction of clots,
Disseminated Intravascular Coagulation cause
DIC TEAR Delivery TEAR: obstetric Infection Cancer: prostate, pancreas, lung, stomach Toxemia of pregnancy Emboli Abruptio placentae Retain fetus products
preeclampsia, obstetric hemorrhage, retained dead fetus, critical illness, mucin-secreting adenocarcinoma, acute promyelocytic leukemia, infx/sepsis (gram - bacteria), massive tissue injury, intravascular hemolysis, shock, snakebites
Disseminated Intravascular Coagulation path
release of procoagulants, tissue factors, bacterial components, enzymes/major endothelial injury -> excessive activation of coagulation cascade -> thrombosis of small/medium blood vessels -> activation of fibrinolysis to resolve clots -> fibrin degradation products released into circulation -> interfere w/ platelet aggregation, clot formation
Disseminated Intravascular Coagulation RF
sepsis, cancer, blood transfusion reaction, pancreatitis, liver disease, surgery, anesthesia,
Disseminated Intravascular Coagulation comp
thromboembolism, tissue hypoxia, infraction, hypoxia of kidney, liver, lung, brain
Hemophilia A def
a condition where clots hemostasis is impaired leading to increased bleeding
Hemophilia A cause
X-linked recessive mutation F8 gene
Hemophilia A path
quantitative/qualitative deficiency of factor VII -> insufficient activation of the intrinsic pathway -> defect in common coagulation pathway -> increased tendency for bleeding
Hemophilia A RF
male
Hemophilia A comp
intracerebral hemorrhage, stroke
Hemophilia A clinical
asymptomatic
easy bruising, prolonged bleeding, hematomas, muscle hematomas, hemophilic pseudotumor, GI bleeding, hematuria, severe epistaxis, joint irregularity and disability,
Hemophilia B def
deficiency in clotting factors
Hemophilia B cause
mutation of F9 on X chromosome
Hemophilia B path
qualitative/quantitative deficiency of coagulation factor IX -> insufficient activation of intrinsic coagulation pathway -> impaired hemostasis
Hemophilia B comp
intracerebral hemorrhage, stroke
Hemophilia B RF
genetics, male
Von Willebrand Disease def
defective platelet function w/ normal platelet count
Von Willebrand Disease cause
autosomal dominant/recessive
Von Willebrand Disease path
quantitative/qualitative deficiency of vWF -> impaired platelet aggregation, adhesion, dysfunction of factor VII -> deficiency in coagulation cascade -> bleeding tendency
Von Willebrand Disease RF
genetics
Von Willebrand Disease comp
severe bleeding, pregnancy probs
Von Willebrand Disease clinical
asymptomatic
surgery/trauma bring on
spontaneous epistaxis, easy bruising, excessive bleeding from wounds, bleeding gums, menorrhagia, GI bleeding, internal/joint bleeding
Immune Thrombocytopenic Purpura def
autoimmune condition where body makes antibodies to thrombocytes/platelets
Immune Thrombocytopenic Purpura cause
Acute: children after viral infx
Chronic: females of reproductive age, no underlying trigger, or by hepatitis C, HIV, lupus
Immune Thrombocytopenic Purpura path
IgG antibodies from the spleen -> bind to GPIIb/IIIa on platelet -> target for destruction of platelets in spleen
Immune Thrombocytopenic Purpura clinical
asymptomatic
purpura (red/purple spots small)
Immune Thrombocytopenic Purpura RF
women, no vaccination,
Immune Thrombocytopenic Purpura comp
hemorrhage
Immune Thrombocytopenic Purpura clinical
asymptomatic
purpura (red/purple spots small)
epistaxis
Vitamin K Deficiency def
lack of Vit K
Vitamin K Deficiency cause
exclusive breastfeeding, medication, lack of Vit K1 prophylaxis at birth, malabsorption, low intake, diseases of SM intestine, liver, gallbladder, pancreas
Vitamin K Deficiency path
↓ phylloquinone ( vit K) -> ↓ bile salts make fat soluble vitamin soluble -> ↓ incorporation into GI micelles -> ↓ absorbed by small intestine -> ↓ integrated into chylomicrons -> ↓ transported to portal circulation -> ↓ liver use to synthesize coagulation factors, other essential proteins
Vitamin K Deficiency RF
infants: no K1 prophylaxis, immature liver, low K stores, sterile gut, maternal ingestion of coumarin-like anticoagulants/some anticonvulsants/antibiotics,
adults: prolonged diarrhea, antibiotics, low intake, TPN administration
Vitamin K Deficiency comp
intracranial hemorrhage, impaired bone mineralization, vascular calcium deposits
Vitamin K Deficiency clinical
low bone density signs, gingival bleeding, epistaxis, easy bruising, hematuria, melena, umbilical stump/circumcision site bleeding, vomiting, seizures
Acute Lymphoblastic Leukemia (ALL) def
uncontrolled proliferation of partially developed white blood cells/lymphoblasts, cancer
Acute Lymphoblastic Leukemia (ALL) cause
B cell: translocation (12,21) and (9,22) Philadelphia chromosome
T cell: NOTCH1 mutation
abnormal chromosome number
Acute Lymphoblastic Leukemia (ALL) path
mutations -> loss ability to differentiate into mature blood cells -> stuck in blast cells -> don’t function effectively and divide uncontrollably -> other cells get crowded out -> leading to anemia, thrombocytopenia, and leukopenia -> blast cells spill into blood travel to thymus, lymph nodes, liver, spleen to enlarge
Acute Lymphoblastic Leukemia (ALL) RF
young age
down syndrome
radiation exposure
alkylating chemotherapy
Acute Lymphoblastic Leukemia (ALL) comp
intracranial hemorrhage
Acute Lymphoblastic Leukemia (ALL) clinical
Fever, fatigue, SOB, pallor, bruising, petechiae, epistaxis, Bone pain, Hepatosplenomegaly, lymphadenopathy, easy bleeding, inc infx, thymus enlargement
Acute Myeloblastic Leukemia (AML)
def
uncontrolled proliferation of myeloblasts, cancer
Acute Myeloblastic Leukemia (AML) cause
chromosomal translocations (15, 17), myelodysplastic syndrome
Acute Myeloblastic Leukemia (AML) path
mutations -> loss ability to differentiate into mature blood cells -> stuck in blast cells -> don’t function effectively and divide uncontrollably -> other cells get crowded out -> leading to anemia, thrombocytopenia, and leukopenia -> blast cells spill into blood travel to thymus, lymph nodes, liver, spleen to enlarge
Acute Myeloblastic Leukemia (AML) RF
down syndrome
radiation
alkylating chemotherapy
Acute Myeloblastic Leukemia (AML) comp
DIC
Acute Myeloblastic Leukemia (AML) clinical
easy bleeding, inc infx, Fever, fatigue, SOB, pallor, bruising, petechiae, epistaxis, Bone pain, swelling of gums
Chronic Myelogenous Leukemia (CML) def
cancer rapid proliferation of mature granulocytes/precursors
Chronic Myelogenous Leukemia cause
Philadelphia chromosome t(9,22) BCR-ABL gene
trisomy of chromosome
doubling of Philadelphia chromosome
Chronic Myelogenous Leukemia path
mutation -> tyrosine kinase is one -> rapid division of myeloid cells -> spill into blood -> liver spleen cause to swell
Chronic Myelogenous Leukemia RF
adult age, radiation, benzene
Chronic Myelogenous Leukemia comp
Recurrent infections, bleeding
Chronic Myelogenous Leukemia clinical
chronic: asymptomatic, fatigue, weight loss, fever,
accelerated phase: pallor, SOB, splenomegaly, hepatomegaly, lymphadenopathy, recurrent infx, bleeding, petechiae, ecchymoses,
blast crisis: bone pain, fever, anemia, significant splenomegaly, inc bleeding, basophilia
Chronic Lymphocytic Leukemia def
cancer, proliferation of mature, functionally abnormal B lymphocytes in bone marrow and don’t die
Chronic Lymphocytic Leukemia path
mutation -> interfere w/ B cell receptors -> activate tyrosine kinase (bruton’s tyrosine kinase and other) -> prevent maturation and slow death - move to lymph nodes
Chronic Lymphocytic Leukemia clinical
fatigue, SOB, pallor, bruising, petechiae, epistaxis, fever, pneumonia, sepsis, lymphadenopathy
Burkitt’s Lymphoma def
B lymphocyte tumor
Burkitt’s Lymphoma cause
chromosomal translocation t(8,14)
Burkitt’s Lymphoma path
translocation -> Myc gene moved adjacent to IgH promoter sequence -> upregulation of Myc gene -> Myc gene simulates cell growth, metabolism -> increased cell division
Burkitt’s Lymphoma RF
EBV infection, Africa
Burkitt’s Lymphoma clinical
“Starry sky” appearance
Hodgkin Lymphoma def
cancer arising from B-cells
Hodgkin Lymphoma cause
nodular sclerosis
Burkitt’s Lymphoma clinical
“Starry sky” appearance (b-cells w/ no cytoplasm and tingible-body macrophages w/ dead neoplastic cells)
extranodal involvement at jaw (Africa) or ileocecal junction
Subtypes of Classical Hodgkin Lymphoma
nodular sclerosis: most common, nodules surrounded by collagen, lacunar cell
mixed cellularity: b lymphocytes, plasma cells, eosinophils, lymphocytes, neutrophils, histocytes, immunocompromised
lymphocyte-rich: lymphocytes surrounding Reed-Sternberg cells, best prognosis
lymphocyte-depleted: lack of normal lymphocytes, abundance of Reed-Sternberg cells, immunocompromised
Hodgkin Lymphoma cause
mutation in DNA
Hodgkin Lymphoma path
mutation -> cell growth and division
Hodgkin Lymphoma RF
20, 60s< EBV
Hodgkin Lymphoma comp
second cancer
Hodgkin Lymphoma clinical
spread to nearby lymph nodes in a contiguous manner
swollen lymph nodes that are painless, rubbery, non-erythematous, nontender including cervical
supraclavicular and axillary
fever, weight loss, night sweats
Reed-Sternberg cells (binucleated neoplastic B cells)
Non-Hodgkin Lymphoma def
cancer of the B or T cells
Non-Hodgkin Lymphoma cause
chromosomal translocation (14, 18) BCL2 gene, BCL-6 and BCL-2 mutation, Human T-Lymphotropic Virus, chromosomal translocation (11, 14) BCL1 gene
Non-Hodgkin Lymphoma path
mutations -> uncontrolled cell division
Non-Hodgkin Lymphoma RF
old age, smoking, FH,
Non-Hodgkin Lymphoma comp
metastases, respiratory problems
Non-Hodgkin Lymphoma clinical
swollen lymph nodes that are painless, rubbery, non-erythematous, nontender in bone marrow, GI tract, spinal cord, fever, weight loss night sweats
Subtypes of Classical Hodgkin Lymphoma
nodular sclerosis: most common, nodules surrounded by collagen, lacunar cell, young age,
mixed cellularity: b lymphocytes, plasma cells, eosinophils, lymphocytes, neutrophils, histocytes, immunocompromised
lymphocyte-rich: lymphocytes surrounding Reed-Sternberg cells, best prognosis
lymphocyte-depleted: lack of normal lymphocytes, abundance of Reed-Sternberg cells, immunocompromised, rare, 30-37
Nodular Lymphocyte Predominant Hodgkin Lymphoma
abnormal b cells express CD20 & CD 45 and don’t express CD15 & CD30
popcorn cells, large number of lymphocytes cluster around popcorn cells forming nodules
Follicular Lymphoma cause
chromosomal translocation (14, 18) BCL2 gene
Mantel cell Lymphoma RF
male
Marginal Zone Lymphoma RF
older people, H. pylori, hepatitis C
Follicular Lymphoma clinical
waxing/waning lymphadenopathy
Diffuse Large B-cell lymphoma def
b cell lymphoma, aggressive growth of b cells, most common in adults
Diffuse Large B-cell lymphoma cause
BCL-6 and BCL-2 mutation
Mantel cell Lymphoma cause
chromosomal translocation (11, 14) BCL1 gene
Adult T-cell Lymphoma def
proliferation of T cell
Adult T-cell Lymphoma cause
Human T-Lymphotropic Virus
Adult T-cell Lymphoma path
Human T-Lymphotropic Virus RNA -> DNA -> incorporates into T cell DNA -> cancer
Adult T-cell Lymphoma clinical
severe hypercalcemia, bone lesions
Mycosis Fungoides clinical
patch or plaque like lesions that look like fungal infection, Pautrier micro abscesses in the epidermis
Lymphoplasmacytic Lymphoma
bone marrow, lymph nodes, spleen, Waldenstrom macroglobulinemia
Adult T-cell Lymphoma cause
Human T-Lymphotropic Virus
Adult T-cell Lymphoma clinical
severe hypercalcemia, bone lesions
Mycosis Fungoides clinical
patch or plaque like lesions that look like fungal infection, Pautrier micro abscesses in the epidermis, erythroderma
Subtypes of Non-Hodgkin Lymphoma B cell
Lymphoplasmacytic Lymphoma Marginal Zone Lymphoma Mantel cell Lymphoma Diffuse Large B-cell lymphoma Follicular Lymphoma
Subtypes of Non-Hodgkin Lymphoma T cell
Mycosis Fungoides
Adult T-cell Lymphoma
Multiple Myeloma def
cancer of plasms cells in bone marrow
Multiple Myeloma cause
t(14, 11), t( 14,6), deletion of gene TP53 tumor suppressor on chromosome 17
Multiple Myeloma RF
alcohol consumption, obesity, radiation, FH
Multiple Myeloma comp
amyloidosis, renal failure, death, UTIs, pneumonia, hyper-viscosity syndrome
Multiple Myeloma path
bone marrow cells, myeloma cells secrete cytokines, IL6, NF-kB -> promote proliferation, survival myeloma cells -> bone resoprtion, monoclonal free light chains, inhibited hematopoiesis, and IL1beta, TNFalpha -> bone lesions, renal disease, anemia, and high calcium
Multiple Myeloma clinical
CRAB (calcium, renal disease, anemia, bone lesions)
confusion, somnolence, constipation, N, thirst, fatigue, pallor, fever, infections, bleeding, bone lesions, pain, fractures, spinal cord compression, paresthesia, Bence Jones, Tamm-Horsfall proteins
Babesiosis def
infection of RBC by Babesia microti, ducani, or divergems
Babesiosis cause
Ixodes scapularis tick, contaminated blood transfusion
Babesiosis def
infection of RBC by Babesia microti, ducani, or divergems
Babesiosis RF
endemic area, May-September, blood transfusions, >50, male, asplenia, malignancy, HIV/AIDS, immunosuppressive drugs, coinfection w/ Borrelia and/or Anaplasma, premature birth
Babesiosis comp
CHF, noncardiac pulmonary edema, acute respiratory distress syndrome, splenic infarct, splenic rupture, septic shock, MI, disseminated intravascular coagulation, death
Babesiosis clinical
asymptomatic, fatigue, fever, chills, headache, myalgia, arthralgia, anorexia, N, cough, hypotension, poor prefusion, pulmonary edema, acute renal failure, disseminated intravascular coagulation
Babesiosis clinical
asymptomatic, fatigue, fever, chills, swears, headache, myalgia, arthralgia, anorexia, N, cough, hypotension, poor prefusion, pulmonary edema, acute renal failure, disseminated intravascular coagulation
maltese cross
Plasmodium species (Malaria) def
single cell parasites that get spread by mosquitoes
Plasmodium species (Malaria) cause
P. falciparum, P. vivax, P. malariae, P. ovale, P. knowlesi
Plasmodium species (Malaria) cause
P. falciparum (few days), P. vivax, P. malariae (few weeks), P. ovale, P. knowlesi
Plasmodium species (Malaria) path
P-infected female anopheles mosquito hunts for a blood meal in evening -> Plasmodium is in a sporozoite stage in salivary gland -> mosquito’s proboscis piece skin sporozoites spill into bloodstream -> liver start asexual reproduction called schizogony -> over 1-2 weeks P. falciparum, malariae, knowlesi multiply asexually & mature to merozoites -> 1 mon-years P. ovale and vivax go dormant -> merozoites bind to duffy receptor on all different stages of RBC –> asexual reproduction 2-3 days -> trophozoite -> late trophozoite -> hemozoin/schizont -> replication -> release into RBC -> some turn into gametocytes and taken up by mosquitos -> mature and fuse into a zygote in gut -> ookinete -> oocyst rupture releasing sporozoites -> into salivary gland
Plasmodium species (Malaria) clinical
paroxysm of fevers P. falciparum (variable), P. vivax (48 h), P. malariae (72), P. ovale (48), P. knowlesi (24 h)
Plasmodium species (Malaria) comp
death, organ failure, cerebral malaria (altered mental status, seizure, coma), diarrhea, jaundice, vomiting, liver failure
Plasmodium species (Malaria) clinical
paroxysm of fevers P. falciparum (variable, worst infx), P. vivax (48 h), P. malariae (72), P. ovale (48), P. knowlesi (24 h)
fatigue, headaches, jaundice, splenomegaly,
Susan just headed for fiji
Schistosomiasis def
parasitic flatworms that cause damage in the mesenteries of the bladder
Schistosomiasis cause
Schistosoma haematobium, S. japonicum, and S. mansoni
Schistosomiasis path
Schistosoma eggs are eleminated in feces or urine into water -> eggs hatch and release miracidia -> miracidia penetrate snail tissue -> sporocyst develop in snail -> free-swimming cercariae released from snail into water -> cercariea penetrates skin -> cerciarea loses tails during penetration and becomes shcistocomulae -> migration to liver through circulation -> adult form -> migration to mesenteric venules/vesical venous plex -> egg deposit -> inflammation -> fibrosis
Schistosomiasis RF
male, rural areas, contact w/ fresh water bodies in endemic areas
Schistosomiasis comp
bacteremia, infertility, intestinal obstruction, nephrotic syndrome, renal failure, cardiomegaly, acute myelopathy
Schistosomiasis clinical
Acute: pruritic papular/urticarial rash of legs/feet, fever, urticaria, chills, arthralgia, myalgia, headaches, angioedema, dry cough, abdominal pain, diarrhea
chronic: abdominal pain, poor appetite, diarrhea, hepatosplenomegaly, portal HTN, ascites, dyspnea, cor pulmonale, hematuria, pyuria, dysuria, frequency, seizures, sensory/motor impairment, cerebellar syndrome
Plasma cell Microscopic Anatomy
clock face chromatin distribution and eccentric nucleus,
Plasma cell Origins
spleen and lymph node
Plasma cell Maturation
bone marrow
Plasma cell function
large amounts of antibody specific to particular antigens
Plasma cell regulation
transcription factors
Plasma cell synthesis
antigen-activated B in spleen and lymph node -> plasmablast -> plasma cells
Plasma cell degradation
2-3 days
How does hepcidin effect iron levels in body?
inhibits ferroportin-1
