nlme hemato&re
DESCRIPTION
Thai TextTRANSCRIPT
National License: Infectious disease
PAGE 36NMLE step I
NL: Hematology and RE system.. Encoded by Waen32, Tai231, New73 MED34Printed by Ying246, Nan247, and Chi-mo unions MED34
Overview
2 Term 2 Serum ( Coagulating factors) Plasma ( Coagulating factors )
Serum expose Coagulating factor Clot Coagulating factors Fibrinogen Plasma Anticoagulant RBC Buffy coat WBC platelet plasma Coagulating factor
Vascular mesoderm Hemangioblast mesenchymal cell differentiation Growth factors Growth factor 2 series Myeloid/Erythroid series Lymphoid series 2 series mature cell Cell Myeloid series Erythrocyte RBC Serie Myeloid cell Megakaryocyte Cell Cytoplasm platelet thrombocyte
Granulocyte neutrophil, monocyte, eosinophil, basophil lymphoid sense bone marrow differentiation lymphocyte B lymphocyte plasma cell immunoglobulin ( Ig light chain-heavy chain ) lymphocyte thymus gland T lymphocyte NK Cell lymphoid stem cell
Erythrocyte (RBC) O2 Tissue Aerobic respiration ATP Cell Cell RBC Anemia Tissue O2 metabolism anemic symptoms
Megakaryocyte Cytoplasm platelet Hemostasis Mast Cell eosinophil allergen Neutrophil lysosome cell lysosome enzyme cell margination migration inflammation enzyme neutrophil Oxidation free radical signs of acute inflammation Monocyte Neutrophil phagocytic activity monocyte Chronic inflammation (neutrophil acute inflammatory process ) monocyte tissue macrophage dendritic cell macrophage Kpffer cell Langerhans cellB lymphocyte lymphoid cell bone marrow plasma cell immunoglobulins antibodies organism HIR autoantibodies SLE T lymphocyte lymphoid cell bone marrow mature thymus CMIR T lymphocyte CMIR defect intracellur organism HIV infection CD4+ T cell AIDS PCP (Pneumocystis carinii pneumonia) Pneumocystis jiroveci CMIR CMIR
8 yolk sac liver bone marrow bone marrow long bone flat bone bone marrow flat bone skull, sternum, pelvis
bone marrow biopsy pelvic bone histology bone marrow fat cell red bone marrow fat yellow marrow massive blood loss acute hemolysis yellow marrow red bone marrow
Red bone marrowWhite (Yellow) bone marrow
bone marrow () bone marrow fetus thalassemia hemolysis RBC bone marrow bone marrow liver spleen hyperplasia hepatosplenomegaly extramedullary hematopoiesis
RBC bone marrow 120 spleen mature RBC biconcave shape nucleus membrane structure cytoskeleton actin myosin RBC 7 m small lymphocyte
RBC nucleus DNA RNA mitochondria RBC Glycolysis anaerobic respiration pathway Pentose-Phosphate pathway (PPP)
Enzyme PPP G-6-PD enzyme NADP+ NADPH free-radical G-6-PD deficiency Oxidative stress G-6-PD enzyme antioxidant metabolite free radical infection oxidative stress sulfa free-radical acute hemolytic crisis
RBC membrane cytoskeleton ABO antigen glycoprotein blood group
antibody antigen blood transfusion O
RBC O2 condition O2 tissue RBC O2 tissue O2 O2 O2 tissue O2 RBC O2 (O2 affinity) O2 dissociation curve
Oxyhemoglobin hemoglobin O2 (hemoglobin O2 deoxyhemoglobin) deoxyhemoglobin 48 g/litre cyanosis
Oxyhemoglobin O2 saturation sigmoid curve 2,3-DPG
2,3-DPG Hb Hb O2 Hypoxia acidosis H+ RBC O2 O2 alkalosis ,H+ Hb O2
Structure Hemoglobin Heme globin chain heme protoporphyrin Fe2+ Fe2+ RBC globin malnutrition globin
Globin protein , , , globin liver, yolk sac, spleen Hb F bone marrow , Hb A Hb F Hb A
, RBC morphology spleen gene thalassemia 2 globin , chain DNA nucleotide Hb E
-gene -globin -globin -thalassemia -gene mutation -globin -thalassemia thalassemia imbalance , -thalassemia ,
Pathophysiology of -thalassemia -thalassemia -gene -globin Hb A Hb F U -thalassemia Hb F U hemolysis structure RBC extravascular hemolysis hypersplenism anemia RBC Heme porphyrin metabolism bilirubin organ jaundice blood transfusion RBC hemolysis anemia iron overload organ organ dysfunction hemochromatosis pancreas chronic pancreatitis B-cell, liver liver cirrhosis, Heart failure, pituitary gland Hypopituitarism
RBC hemolysis RBC bone marrow (BM), liver, spleen BM Bone Thalassemia hemochomatosis DM pituitary gland GH Sex hormone sex organ
X-ray linear fracture
ANEMIA
Anemia criteria WHO condition Hb Hct Testosterone RBC Hb 13 mg% 12 mg% 11 mg% Blood volume
Mechanism Anemia 3
1. RBC BM aplastic anemia RBC histopathology fat BM Renal failure Erythropoietin hormone RBC anemia of chronic kidney disease
RBC Iron deficiency, Folic deficiency, B12 deficiency DNA Malnutrition: globin chain RBC 2. RBC hemolysis hemolysis 2 UIntravascular hemolysisU RBC RBC membrane G-6-PD deficiency malaria
UExtravascular hemolysisU RBC Thalassemia
3. Blood loss UAcute blood lossU trauma UChronic blood lossU GI bleeding NSAIDs, aspirin Gastritis Blood smear Hypochromic-microcytic RBC Iron deficiency Blood smear iron deficiency CA Colon Bleeding Tumor
anemia sign & symptom 2 CVS CNS fatigue, dyspnea on exertion, (RBC, (carry O2, tissue hypoxia, pump O2 Heart failure
CNS O2 Dizziness Confusion Coma (Onset) Trauma bleeding anemic symptom
Anemia 2 Onset Acute () Chronic () 3 acute 3 Chronic Acute acute blood loss acute hemolysis RBC 120 Chronic
acute blood loss (epistaxis), GI bleeding oxidation coffee ground melena
acute hemolysis jaundice Direct bilirubin urobilinogen Intravascular hemolysis Hb Hemoglobinuria G-6-PD with acute hemolysis
Chronic anemia chronic blood loss BM failure aplastic anemia WBC infect platelet 2 precursor iron deficiency, chronic renal failure, vitamin B12 defect megaloblastic anemia [ Nucleus RBC Cytoplasm nucleus RBC Cytoplasm ] vitamin B12 jejunum absorb malabsorption Capillaria philippinensis malnutrition diarrhea ileum TB infect vitamin B12
Chronic hemolysis thalassemia autosomal recessive (G-6-PD deficiency X-linked recessive )Clinical manifestations of anemia
: mucous membrane conjunctivae , , systemic hypertension Tachycardia compensate O2 tissue requirement1. Glossitis () Folic acid Vitamin B12
2. Koilonychia (spoon shape nail) iron deficiency
** Glossitis Koilonychia iron deficiency**3. Angular dermatitis nutritional deficiency anemia 2
4. Petechiae hemorrhage petechiae bone marrow
** (anemia) petechiae Bone marrow failure**
Icteric scleraMongoloid facies
Hemolytic jaundice hemolytic anemia chronic extravascular hemolytic anemia Thalassemia Thalassemic facies Mongoloid facies
Hemolytic blood picture: hemolysis spherocyte central pallor polychromasia
thalassemia hemolysis spherocyte polychromasia Iron deficiency anemia hypochromic-microcytic RBC (microcytic) RBC MCV (Mean corpuscular volume) 80-100 fL , clinical CBC CBC, blood smear microcyte iron deficiency, thalassemia, lead poisoning macrocytic MCV > 100fL megaloblastic anemia B12, folate deficiency
hypersegmented PMN B12 deficiency
Pernicious anemia B12 Intrinsic factor Parietal cell stomach megaloblastic anemia ( Intrinsic factor)
UU B12 (cobalamine) R factor pancreatic enzyme R factor B12 B12 Intrinsic factor terminal ileum absorption , enzyme , Terminal ileum Vitamin B12 deficiency UClinical B12 deficiencyU: , neurologic symptom
BLEEDING DISORDERS
hemostasis 2 Primary hemostasis platelet plug vasoconstriction blood flow contact collagen tissue platelet platelet aggregation platelet plug Secondary hemostasis coagulative pathway intrinsic extrinsic fibrin fibrinolysis clot
coagulation cascade natural anticoagulant clot endothelial injury natural anticoagulant endothelial injury clot
hemostasis platelet, blood vessels coagulation normal physiology injury expose collagen platelet platelet coagulation factors intrinsic extrinsic factors
platelet aggregation 2 1. platelet von Willebrand factor factor VIII vWF deficiency vWF renal failure von Willebrands disease type 1 platelet coagulogram PTT prolong factor VIII 2. platelet Thromboxane A2 metabolism arachidonic acid cyclo-oxygenase ( COX-1 COX-2 ) COX-1 COX-2 inhibit COX inflammation COX-2 COX-1 IL-1 normal function platelet barrier mucous cell mucosa COX aspirin ( COX-1 COX-2) COX-1 platelet dysfunction atherosclerosis Ischemic heart disease Acute myocardial infarction Coronary syndrome bleeding aspirin TA2 aspirin PGE2 COX-1 gastritis mucous secretion gastric mucosa PGE2 prostaglandin renal function
COX-1 bleeding gastritis, peptic ulcer renal dysfunction renal failure inhibit COX-2 aspirin side effect aspirin selective COX-2 inhibitor COX-1 peptic ulcer COX-2 COX-1 TXA2 platelet clot selective COX-2 inhibitor Myocardial infarction platelet vWF, TXA2, ADP ( platelet) factors Coagulation cascade intrinsic extrinsic pathway
pathway interpret lab intrinsic pathway PTT extrinsic pathway PT common pathway factor pathway pathway
Prolong PTT, Normal PT = intrinsic pathway
Prolong PT, Normal PTT= extrinsic pathway
Prolong PT PTT = common pathway
common pathway factor X factor II ( factor II (prothrombin) factor IIa (Thrombin)) fibrinogen fibrin polymer clot fibrinogen Thrombin time
3-4 factor Coagulation pathway factor VII tissue factor tissue injury tissue factor factor VII factor X common pathway thrombin platelet factor VII coagulation pathway factor VII fibrin tissue plasminogen activator (tPA) plasminogen activated form plasmin fibrin natural anticoagulant
Natural anticoagulant clot DIC clot O2 anaerobic respiration lactic acidosis
Natural anticoagulant clot Protein C, Protein S, Antithrombin III Coagulation factors
Procoagulants regulators coagulation coagulants coagulants anticoagulants clot deep vein thrombosis coagulation anticoagulation bleeding
bleeding primary hemostasis secondary hemostasis fibrinolysis activity ()1) UPrimary hemostasisU: platelet dysfunction onset mucosal bleeding mucous membrane (petechiae) superficial ecchymosis platelet pancytopenia aspirin platelet dysfunction
2) USecondary hemostasisU: coagulation process Hemophilia mucosal bleeding (hemarthrosis) visceral organs deep ecchymosis, hematoma
clinical presentation (petechiae) conjunctiva hypermenorrhea clot clot (Venous stasis) clot endothelial injury vasculitis clot hypercoagulable stage activity clot Risk factors vascular thrombosis UVirchows triad clot thrombophilia (thrombo- = thrombus, philia = ) congenital natural anticoagulant ( Protein C, Protein S, Antithrombin III) acquire thrombophilia condition thrombosis venous thrombosis Antithrombin III nephrotic syndrome proteinuria natural anticoagulant thrombosis Deep vein thrombosis clot emboli deep vein thrombosis pulmonary embolism
deep vein thrombosis emboli cerebral stroke vein common carotid artery venous site venous emboli capillary arterial site arterial occlusion Right-to-left shunt ASD Venous thrombi venous site left atrium left ventricle systemic circulation stroke stasis intravenous pressure tissue tissue ulcer
Venous ischemic ulcerHemophilia
hemophilia clinical (hemarthrosis) coagulation
Hemophilia coagulation defect 2 type A factor VIII type B factor IX type A X-link recessive
factor VIII factor IX intrinsic pathway PTT prolong hemophilia activity factor ( factor 15-45%) bleed injury factor activity 1 diaphragm
Stage 3: lymphoma 2 diaphragm
Stage 4: lymphoma
Leukemia
2 type Leukemia myeloid lymphoid tissue type acute chronic acute leukemia blast cell BM >20% ALL AML ALL AML Bone Marrow failure syndrome anemia bleeding
Organomegaly tumor cell deposit monoblastic leukemia
Hyperuricemia cell (note: cell hyperuricemia )
Bone pain tumor cell BM
Note: APL (acute promyelocyctic leukemia AML type M3) DIC ( Auer rods)
UU: BM transplant, chemotherapyMultiple myeloma (MM)
Second most common hematologic malignancy ( lymphoma, leukemia) plasma cell bone marrow (BM) Bone marrow biopsy plasma cell
Note: tumor plasma cell organ Bone Marrow plasmacytomaU Multiple MyelomaU:
plasma cell BM monoclonal Ab (M protein) serum monoclonal Ab Ab heavy chain light chain light chain light chain urine Bence Jones protein Bence Jones protein acute renal failure plasma cell BM cell BM (bone marrow failure) WBC , RBC anemia, platelet bleeding plasma cell BM cytokine TNF osteoclast , Ca2+ hypercalcemia cytokine Light chain Ab amyloid deposit amyloidosis organomegaly ( deposit ), UNoteU: clinical Multiple Myeloma CRAB (C = hypercalcemia, R = renal involvement, A = anemia, B = bone pain)UU: plasma cell bone marrow > 10%, serum monoclonal Ab ( Ig G Ig A, Ig M, Ig E, Ig D ), Bence Jones proteinUU: BM transplant, chemotherapyMyeloproliferative disorder
4 CML (WBC ), polycetemia vera [PV] (RBC ), essential thrombocytosis [ET] (platelet ), myelofibrosis extramedullary hematopoiesis myeloproliferative disorder normal differentiation blast cell
Chronic Myeloblastic Leukemia
myeloproliferative disorder WBC translocation (9;22) Philadephia chromosome BCR-ABL gene gene tyrosine kinase myeloid cell
CML 3 phase 1. chronic phase organomegaly ( ) peripheral blood smear blast cell
2. accelerated phase 3. blastic phase blast cell BM >20% acute leukemiaUU: Philadephia chromosome [ BCR-ABL gene ]UU: chemotherapy, targeted therapy imatinib tyrosine kinase tyrosine kinase cellPolycythemia Vera
RBC erythropoietin RBC RBC (erythrocytosis)
UClinicalU: erythrocytosis hyperviscosity syndrome O2 (hypoxia) O2 , nerve O2 nerve nerve () blood clot UU: erythrocytosis serum erythropoietin ( RBC erythropoietin erythropoietin) erythrocytosis hypoxia ( COPD) erythropoietin serum erythropoietin Essential ThrombocytosisUU: platelet platelet
UClinicalU: platelet hyperviscosity syndrome hypoxia blood clot ( - -) bleeding platelet von Willebrand factor von Willebrand factor deficiency Platelet dysfunction
UU: ET blood clot bleeding Practice
1. Clinical
a. Red blood cell
b. White blood cell
c. Platelet
d. Coagulation
lingual papilla glossitis (spoon-nail) Iron deficiency RBC
Clinical signs Thalassemia RBC
SHAPE \* MERGEFORMAT
Histology Parietal cell RBC intrinsic factor Vitamin B12 Megaloblastic anemia
muscle wasting wrist drop Clinical presentation Lead poisoning RBC
Axillary node enlargement RE system WBC
deep vein thrombosis coagulation cellulites
Jaundice CT infiltration Cholangiocarcinoma obstructive jaundice Biliary tract Bleeding disorder Vitamin K deficiency Coagulation
2. WBC
Acute appendicitis neutrophil
Trichinellosis encapsulated cyst cross-section
eosinophil allergy asthma eosinophil infiltration eosinophil
Caseous granulomatous inflammation monocyte lymphocyte Granuloma TB infection Langhans giant cell
3. 55 GI Hb 10 mg/dL MCV 72 fL, serum iron TIBC saturation ferritin A. RBC folate
B. Iron absorption studies
C. Colonoscopy
D. Bone marrow examination
Colonoscopy CA colon bleeding Anemia4. 60 2 Lost proprioception in lower extremities positive Romberg sign, vitamin A. Folic acid
B. Thiamine
C. Vitamin K
D. Vitamin B12
Vitamin B12 deficiency Romberg test proprioceptive sensation posterior column of spinal cord sensory ataxia peripheral neuropathy loss of proprioception
Folic acid megaloblastic anemia
Thiamine Beri-beri, Wernicke-Korsakoff syndrome
Vitamin K Bleeding5. 25 5 CBC: platelet count 230,000 PT PTT mildly prolong A. Hemophilia
B. vWF disease
C. ITP
D. Cirrhosis
Hemophilia hypersplenism mucosal bleeding Platelet Platelet dysfunction mild PTT prolong vWF disease vWF Factor VIII intrinsic pathway Factor VIII PTT prolong6. A 14-year-old boy present with laceration on his hand that has become badly infected. He has felt fatigued for sometime. Physical examination reveals pallor of the mucous membranes in addition to bleeding on the inside of his cheeks. He has petechiae covering his body, and patches of purpura on his thighs, trunk, and arms. Relevant laboratory findings are WBC count 2,700 cells/mm3, Hct 22% and Platelet 4,800 cells/mm3A. Aplastic anemia
B. Acute leukemia
C. lymphoma
D. Megaloblastic anemia
WBC abnormal bleeding CBC Aplastic anemia
Acute leukemia WBC Blast cell 7. A 42-year-old man presents to ER department with sudden onset of shortness of breath. He complains of feeling fatigued and weak, and notes he saw blood in his urine. He is being treated with cotrimoxazole for UTI. Physical examination reveals mild icteric sclera and tachycardia, no hepatosplenomegaly
A. G-6-PD deficiency with crisis
B. Hb H with crisis
C. Aplastic anemia
D. Iron deficiency
G-6-PD deficiency with crisis
Hb H with crisis 8.
SHAPE \* MERGEFORMAT
Lead poisoning basophilic stipping Lead line fatigue wasting, neuropathy extensor area wrist drop wrist drop
organomegaly
extramarrow cellular infiltrate
Infection bleeding
leukemic cells in peripheral
anemia thrombocytopenia neutropenia
abnormal adhesion molecules
bone pain
ineffective hematopoiesis
Acute marrow expansion and replacement of blastic cells
(Bone marrow failure)
hypercellular marrow with < 5-10% blasts
myeloproliferative
disorders
hypercellular marrow with predominantly immature form >20%
acute leukemia
Abnormal proliferation
and differentiation
Myeloid stem cells
organomegaly
thrombosis bleeding extramedullary hematopoiesis
cytopenia, extramedullary hematopoiesis (organomegaly)
myelofibrosis
CML, PV, ET
Infection, anemia, hemorrhage
peripheral cytopenia with varying blasts and without organomegaly
chronic marrow expansion with released cells to periphery
hypercellular marrow with excessive blasts 5-20%
dysplastic changes, apoptosis
myelodysplastic syndrome
lymphoma / leukemia
Abnormal proliferation
and differentiation
Abnormal proliferation
Normal differentiation
Normal proliferation
Abnormal differentiation
Lymphoid stem cells
Hematopoietic stem cells
Chronic Lead Poisoning