211 Hema I Final.pdf

Blood Components Blood is a liquid tissue. Cells (45%) • • • Plasma (55%) Erythrocytes (~99%) Leukocytes Thrombocytes • • • • • • • • • Water Proteins Glucose Cholesterol Calcium Hormones Metabolic waste Antibodies Many others… Erythrocytes (RBCs) Erythrocytes are non-dividing cells that transp...

Blood Components Blood is a liquid tissue. Cells (45%) • • • Plasma (55%) Erythrocytes (~99%) Leukocytes Thrombocytes • • • • • • • • • Water Proteins Glucose Cholesterol Calcium Hormones Metabolic waste Antibodies Many others… Erythrocytes (RBCs) Erythrocytes are non-dividing cells that transport O2 and CO2. There are 250M hemoglobin and 1 billion O2 molecules per RBC. They contain no nuclei or mitochondria. Adult sites of production • • • • Removed by MononuclearPhagocyte System (MPS) Vertebrae Pelvis Sternum Ribs Growth Requirements • • • Spleen Liver Lymph nodes Stimulating Factors • • • Folate B12 Iron (helps hold O2) Protein (helps hold O2) Vitamins (needed for RBC DNA synthesis) • • • • • • • • Iron & protein deficiencies: lead to reduced O2 carrying capacity Vitamin deficiencies: lead to impaired DNA synthesis in RBCs Erythropoiesis (RBC production) Regulated by O2 levels in the blood. Entire process takes ~4 days. • • • Erythropoietin (EPO) production is stimulated by hypoxia. EPO is produced by peritubular cells of the kidney EPO induces RBC production in the bone marrow Hematocrit (% of blood that is RBCs) Convenient way to determine if RBC count is normal. Blood sample is centrifuged and measured. Normal Values Males 42-50% Females 39-48% Hemorrhage Damage to bone marrow High altitude Exercise Hemolytic disease Low hemoglobin levels Anemia Definition Reduced circulating RBC levels. Reduced O2 carrying capacity can ultimately lead to ischemia. Anemic Values Males <42% Hematocrit Hb <13.0 g/100mL Females Hb <12.0 g/100mL <39% Hematocrit Prevalence • 2018 → 18.32M Causes 5 . 6 % o f A m e r i c a n s h a v e a n e m i a • • • • • • • • Symptoms Iron deficien cy (3050%) Blood loss Nutritio nal deficien cies Medicat ions/Dr ugs/Che mo Autoim mune disease End stage renal failure Cancers GI absorpti on disorder s • • Dx O v e r a l l w e a k n e s s T a c h y c a r d i a Tx • Low RBC levels C B C w i t h d i f f e r e n t i a l • • • S u p p l e m e n t s M e d i c a t i o n s M a n a g America ns • • Bone marrow disorder s Spleno megaly • • • • • • F a t i g u e D y s p n e a P a l p i t a t i o n s A n g i n a P a l l o r M y e l i n d e g e n e r a t i o n e u n d e r l y i n g d i s o r d e r 3 Main Ways to get Anemia 1) Reduced RBC production 2) Excessive blood loss (hemorrhage) 3) Increased RBC destruction (hemolysis) Epidemiology of Anemia Worldwide United States 25% of population 42% of pregnant women 30% of nonpregnant women 13% of men • • • • • • • • 5.6% of the population 8.8% of the pregnant women 5-7.6% of the nonpregnant women 2-3.5% of men Prevalence by Race AA (15%) > Hispanic (5%) > White (4%) Types of Anemia There are over 400+ types! • • • • • • • Iron deficiency anemia (IDA) (50%) Anemia of chronic disease (ACD) (33%) Pernicious anemia (PA) (2%) Folate deficiency anemia (FDA) (<1%) Lead poisoning anemia (LPA) Aplastic anemia (AA) Hemolytic (HA) Sickle cell anemia (SCA) (12%) Anemia Classification Etiology • • Size Hemoglobin Content • Macrocytic B12, Folate • Microcytic Iron (Fe), lead (Pb) • Normocyti c Sickle cell Hypoproliferativ e Hemolytic • Normochromi c B12, folate, sickle cell • Hypochromic Iron, lead Microcytic (MCV <80fL) Normocytic (MCV 80-100 fL) Macrocytic (MCV >100 fL) Iron deficiency Hemolytic Folate (B9) deficiency Sideroblastic SS/SC Anemia B12 deficiency Lead (Pb) Aplastic Copper deficiency Thalassemia's Chronic Renal Disease Drug-induced Posthemorrhagic EtOH abuse Anemia of Chronic Disease Liver disease Hypochromic Normochromic Hyperchromic Iron deficiency B12 deficiency Does not exist Lead (Pb) Folate (B9) deficiency Sideroblastic SS/SC Anemia Thalassemia's Aplastic Posthemorrhagic Hemolytic Anemia of Chronic Disease Microcytic-Hypochromic Anemia Iron Deficiency Anemia (IDA) (Most common type of anemia worldwide & USA) Risk Groups Main Causes Dx Tx • • • Poo r Wo me n Chil dre n • Pregnan cy & Heavy menstru ation (females ) • C B C d i f f • Address bleeding & iron supplemen tation Can cause cognitive impairments • • • Chronic, slow GI bleeds (men) Poor GI absorpti on (Celiac disease) Poor diet Hematoc rit Lead Poisoning Anemia (LPA) Lead inhibits heme & globin synthesis of RBCs, leading to anemia. Risk Groups Early S&S Late S&S • Chil dren @ high est risk Ingestion of leadcontaining paint chips • Livin g in olde r hom es • • • Pallor Abnor mal pains Irritab ly • • • Letharg y Anorexi a Slurred speech & Convuls ions Tx • Remo ve lead sourc e • Chela tion Chelating agent binds lead ion, removing it Macrocytic-Normochromic Anemias Pernicious Anemia (PA) (IF deficiency is more common than folate deficiency) Reduced levels of intrinsic factor (IF) can lead to a deficiency in vitamin B12. • • IF is a transporter located in the gut responsible for B12 absorption. Vitamin B12 deficiency leads to impaired DNA synthesis during erythropoiesis. Prevalence Other Causes Tx • • Mean pt age ~60 • Autoimmune & Malabsorption Disorder Crohn's, Celiac disease, etc. • H. pylori infection • ETOH use • PPI use • Diet (vegetarians) B12 Injections Folate Deficiency Anemia (FDA) Folate (Vit. B9) is obtained through dietary sources. Vitamin B9 is a co-enzyme involved with DNA synthesis in RBCs. Deficiency is also associated with neural tube defects in fetuses. Prevalence Causes • Tx • • Rare in USA due to dietary regulation s Folate included in most foods Poor diet Autoimmune & malabsorptio n disorders Ex) Gastric bypass • • Oral supplement s Diet changes Normocytic-Normochromic Anemias Anemia of Chronic Disease (ACD) (2nd most common cause of anemia worldwide & USA) Usually occurs in older adults (common in nursing homes) Chronic inflammatory diseases can slowly impact RBC health, leading to anemia. Prevalence Causes Associated with… Tx • 24 % of adu lts >65 yo hav e ane mia • • AIDS Autoim mune (RA or SLE) • DM • Hepatitis • Chronic kidney disease • • • Aplastic Anemia (AA) Bone marrow is replaced with fibrous, fatty tissue. Abrupt onset of low blood cell counts leads to pancytopenia Leads to increased incidence of infections and hemorrhages. Often occurs in healthy, young adults. Decreas ed RBC lifespan Suppre ssed product ion of EPO Altered iron metabo lism • • Tx underl ying conditi on Oral EPO Etiology Tx • • Idiopathic (75%) Secondary (Drugs, Virus, Autoimmunity) Chloramphenicol, arsenic, chemo • Bone marrow transplant Hemolytic Anemias (HA) Premature destruction of RBCs Signs & Symptoms • • • Fatigue Jaundice Redbrown urine Types • Intrinsic (Inherited Deficiencies) Hemoglobinopathies (Sickle Cell disease & Thalassemias) RBC membranes Enzyme defects • Extrinsic (Toxic/Antibody damage to the circulating RBC) Autoimmune/medications (Cephalosporins, NSAIDs, SLE) Mechanical damage (heart valve abnormalities, trauma) Incorrect blood type (A,B,O) transfusion (severe) Hemoglobinopathies (Sickle Cell Anemia & Thalassemia) Inherited disorders affecting hemoglobin formation Sickle Cell Genotypes Genotype Percentage AS (trait) 66% AC (trait) 16.6% Thalassemia trait 12.45% SS 3% SC 2% Thalassemia 0.36% A = Adult (Normal) C = Sickle Cell Sub-type S = Sickle Cell Sub-type Sickle Cell Trait (AS) Found in 8% (1/12) African Americans in the US. Typically asymptomatic due to having one good "A" gene May confer "fitness benefit" against malarial infections. Sickle Cell Disorders (Most common inherited blood disorder) Caused by abnormal hemoglobin synthesis Inheritance is autosomal recessive. Prevalence Life Expectancy Complications • 70k cases in US • AA & Hispanic 1/500 AAs in US • • ~50-60 years 90% live to adulthood • • Hemolytic anemia Intermittent painful "crises" • Multiple organ damage possible (spleen, GI, brain, heart, etc) Sickle Cell Anemia (SCA) (Normocytic-Normochromic Anemia) SCA is caused by a single point mutation in the beta-globulin gene. Stressors can cause "sickling" (such as a viral illness, dehydration, hypoxia, or exertion). Sickling can have multiple effects on the body: • • • Microvascular occlusion Hemolysis (anemia) Eventually → Ischemia! Sickle Cell Retinopathy (SCR) 5 Stages 1. 2. 3. 4. 5. Peripheral arteriolar occlusions Peripheral AV anastomoses "Sea-Fan" neovascularization Vitreous hemorrhage Traction of rhegmatogenous retinal detachment Will NOT ask us the 5 stages! Highest risk for SCR: SC>SS>AS Thalassemias (Microcytic-Hypochromic Anemia; Severe) Thalassemias are cause by absent or reduced globin chains in hemoglobin. Compared to SCD, "sickling" does NOT occur. Unstable globin chains damage the RBC membrane, leading to hemolytic anemia. May also lead to other clinical disorders: • • • • • Cardiac Splenomegaly Endocrine Hepatic Iron overload Alpha-Thalassemia • • Less severe More common in south Asian and west African nations Beta-Thalassemia Severe Often fatal in childhood (Avg 17 yo) Cardiac complications in 71% • Common around the Mediterranean • More likely in the USA than alpha-thal • • Anemia Ocular Manifestations Uncommon findings in anemics, unless severe. Prevalence • • 10% of pts with anemia only 40-70% of pts with anemia & thrombocytopenia Signs • Conjunctival pallor (75%) If RBC count is 50% of normal • Anemic Retinopathy (16-28%) Flame-shaped or dot-blot hemes Roth's spots (most commonly caused by diabetes) • ON/Posterior Pole Pallor (14%) Polycythemia (aka Erythrocytosis) Definition An increase in the RBC mass Anemic Values Males ≥51% Hematocrit Females ≥48% Hematocrit 3 Types 1) Primary Polycythemia (57%) Proliferative disease of the bone marrow (neoplastic) Most common Aka Polycythemia Vera 2) Secondary Polycythemia 3) Relative Polycythemia Increased EPO levels caused by hypoxic conditions Tx by managing the underlying condition - Disease / chronic hypoxia (COPD, sleep apnea, CHF) - Toxins (smoking, carbon monoxide) - Adaptation (high altitude) Loss of vascular fluid (dehydration or diuretics) Tx by hydration Polycythemia leads to increased thrombosis risk! Elevated hematocrit levels can head to hematic hyperviscosity (remember Virchow's triad!) Primary Polycythemia / Polycythemia Vera Caused by a gene mutation at JAK2 locus (95% of cases). Mutation leads to uncontrolled RBC hyperproliferation in the bone marrow (neoplastic). Prevalence Complications • 2.8/10 0k men 2.3/100k women • 22/10 0k popul ation • Dx 50% risk of acut e myel oid leuk emia (AML ) over 20 years Tx • Bl o o d Te st CBC with differential • Phleboto my "Bloodletting" >60-65% hematocrits • Anticoagu lants • Medicatio n Jakafi (Ruxolitinib) Inhibits JAK enzymes Bloodletting Polycythemia Ocular Manifestations (14%) • • • • • • Transient vision loss (40%) Retinal vascular occlusions ION Papilledema Diplopia VF defects Secondary to CVA Retinal Vascular Occlusions VF Defects Papilledema Lab Tests Complete Blood Count (CBC) with Differential Broad screening test to check general health status. Uses Checks for… • • • M o ni t o r tx D ia g n o s e C h e c k g e n e r al h e al t h st a t u s • • • • • • Includes… Ane mia Infec tion Infla mma tion Blee ding disor ders Leuk emia Mor e… • Neutrop hils Lymphoc ytes Monocyt es Eosinoph ils Basophil s W B C C o u n t • Hemoglo bin Hematoc rit Size, volume, shape R B C C o u n t • Size, volume, shape P l a t e l e t C o u n t Summary of CBC Results TEST HIGH LOW WBC Count “Leukocytosis” “Leukopenia” • • • • • • RBC Count • • • • “Polycythemia” • • • • • • • Platelet Count *Infection (viral/bacterial) Inflammation Leukemia Myeloproliferative disorders Allergies Intense exercise/stress **Polycythemia vera *Chronic hypoxia Dehydration Lung disease Excess EPO production Smoking High altitude living “Thrombocytosis” • **Tissue damage surgery, trauma, fractures • *Infection • Cancer • Autoimmune • Hemolytic anemia • Myeloproliferative disease *Immunosuppression Bone marrow disorders Lymphoma Severe infection (sepsis) “Anemia” • *Nutritional deficiency Fe, B12, folate, etc. • Acute/chronic bleeding • Hemolytic anemia • Bone marrow disorder • Chronic renal disease “Thrombocytopenia” • • • • • • *Immune Drugs (APAP, sulfa) Sepsis Leukemia Lymphoma Chemo/Radiation