heme Flashcards
leukopoesis
Starting in the bone marrow, we give rise to all the lineage of the blood products
anemia
-reduction in number of circulating RBC measured by Hemoglobin (Hb) or hematocrit (HCT).
-WHO defines anemia as a hemoglobin concentration of <12.0 g/dL in women and <13.0 g/dL in men.
-3.5 Million Americans have some form of anemia
-MCC of anemia -> iron deficiency
-bc not enough O2
-Fatigue- to the muscle
-Pallor - to the skin
-shortness of breath - to the lungs
-dizziness - to the brain
when do we transfuse
-transfusion symptomatic or <7
-if you know there is a loss and symptoms
-<7 hmg
-TRICC trial 2013
anemia causes
-Blood loss – Acute or chronic
-Blood destruction- Hereditary abnormalities or acquired abnormalities(hemolysis)
-Deficient RBC production- Nutritional or failure of Bone Marrow
-Treatment typically involves addressing the underlying cause and supplementing dietary deficiencies.
erythropoiesis
-process of erythrocyte production
-What stimulates this process -> Hypoxia (Anemia, High altitude, blood loss)
-RBC Arise from erythrocytes in the bone marrow.
-Stimulates Hemocytoblast to synthesize hemoglobin
-Erythropoietin is released by kidney when hypoxia is detected in the blood.
-Condition of the hemoglobin produced can indicate the type of anemia
-hormones that stimulate RBC:
-T3,T4
-erythropoietin
-retic count -> if low we know RBC are not being formed -> is bone marrow working
MCV
-First evaluation of total Hgb/HCT
-Next evaluate Size of the cells- Mean corpuscular volume (MCV)
-Microcytic – MCV <80 Femtoliters (fl)
-Normocytic – MCV 80-100 FL
-Macrocytic- MCV >100 FL
normocytic anemia
-Known as anemia of chronic inflammation
-MCV- Normal (80-100fL)
-Retic count needs to be investigated
-Elevated Retic (>2%)- (RBC Loss) Hemolytic anemia or hemorrhage
-Decreased Retic(<2%)- Aplastic anemia
-Mnemonic :
-A cute Blood loss ( inc retic count)
-B one Marrow (aplastic anemia) (Low retic count)
-C hronic disease/chronic inflammation (kidney, cancer, rheumatoid arthritis, chron’s disease)
-D estruction – hemolysis (intravascular or extravascular)
normocytic anemia - extravascular
Extravascular- Reticuloendothelial system-destruction (Destruction of RBC) in the spleen, Liver and bone marrow
-Autoimmune Hemolytic anemia- auto antibodies
-“Warm” Autoimmune hemolytic Anemia (AIHa)- occurs at body temp. IGG-mediated, can have enlarged spleen or DVTs. COOMBS positive test
-Cold Agglutinin Disease- at low temp. cells clump together and are targeted by complements- IGM mediated. Raynaud phenomenon can occur. Coombs positive test
-Viruses (EBV, HIV, CMV) body produces antibodies that attack rBC
-Parasites (Malaria) distort the RBC and cause RBC to be destroyed by the body
-Hemoglobinopathy- sickle cell, thalassemia, PNH
-Cell membrane defect- hereditary spherocytosis- inc destruction in the spleen
-Enzyme deficiency- G6p deficiency- dec protection from oxidative stress
normocytic anemia - intravascular
Intravascular- (in the vessels) Microangiopathy- TTP, HUS, DIC , Prosthetic valves (shear) Infection, macroangiopathy (Aortic Stenosis-shear of the RBC),transfusion reactions
-Macroangiopathy- Mechanical valve- shear of the RBC-> Schistocytes abnormal shape ->destruction
-Microangiopathy- platelets are clumped together, RBC are sheared trying to pass-> Schistocytes!
-DIC (disseminated Intravascular Coagulation) Gram-neg!! Sepsis, trauma, OB, snake bite
-HUS (Hemolytic uremic Syndrome) triad!!!–anemia, thrombocytopenia, Azotemia, if due to E coli 0157:H7-> Blood in stool. (mostly in children)
-TTP(Thrombotic thrombocytopenic Purpura) anemia, thrombocytopenia, Azotemia, Fever!, AMS IGG antibody!! (Caused by immune response to ADAMTS13 Enzyme which breaks down VWF -> inc in clots in body)
-HELLP- Hemolysis, Elevated LFTS, Low Platelets- unknown what causes the hemolysis
-Malignant HTN- (endothelial damage)
-Complement activation- PND (Paroxysmal Nocturnal hemoglobinuria) complement Mediated intravascular hemolysis- it is an inherited disorder that gets activated by aything that inc. complement activation (surgery, blood transfusion, excessive alcohol/activity)
-Membrane disorders:
-Hereditary spherocytosis
-Hemolytic disease of newborns, jaundice baby at birth-> phototherapy
-Hemoglobinopathy:
-Sickle cell disease
-g6PD deficiency-> oxidative hemolysis
-Loss of oxidative stress protection (Bite cells and Heinz Bodies on smear)
-Wilson’s Disease-ATP7B gene mutation (oxidative destruction)
-Build up of copper in liver, brain, eye leading to tissue damage. (Kayser-Fleischer rings, AMS, high LFTs)
aplastic anemia
-classified into inherited and acquired Aplastic Anemia
-Acquired: (can present at any age)
-In 75% of these cases, the cause of the acquired form is not identified; idiopathic
-In about 25% of the cases of acquired Aplastic Anemia are due to :
-Autoimmune dz: SLE, GVHD
-Pregnancy
-Chemotherapy- wipes out all cells
-Radiation
-Toxins (Benzene, arsenic, organophosphates) -> pesticides
-Drugs: NSAIDS, Sulfonamides, chlorophenicol (gray baby syndrome) antithyroid meds, colchicine (increase doses suppresses proliferating cells)
-Infection: hepatitis, EBV, HIV
-Inherited (usually present in childhood)
-Fanconi syndrome- MC inherited form Aplastic anemia!
microcytic anemia
-MCV <80fl
-Think ”TAILS”
-Thalassemia
-Anemia of chronic disease
-Iron-deficiency
-Lead poisoning- abd pain, wrist and foot drop
-Siberoblastic anemia
thalassemia
-Inherited, defective production of Alpha or beta chains of hemoglobin
-Smear basophilic stippling!!!, iron studies normal!!!
-Beta Thalassemia- MC in Mediterranean, African, Asian population, autosomal recessive ds
-Free alpha chains clump together and damage the cell membrane causing hemolysis
-Smear- hypochromic, microcytic cells w/target cells
-Confirmation done with hemoglobin electrophoresis
-Alpha thalassemia- Silent carrier, mild symptoms
-Excessive transfusions or excessive absorption of blood in the gut can cause Secondary hemochromatosis: tx chelation
-hemochromatosis- increase build up of iron in organs -> impairs
anemia of chronic ds
-Chronic inflammation, infection, cancer
-Iron not available secondary being trapped within macrophages
-Cytokines from the disease process suppress erythropoiesis
-Ferritin is high, TIBC low
lead poisoning
iron deficiency anemia
-MC microcytic anemia
-Nutrient deficiency- #1 cause
-IDA is usually the first sign of Hyperthyroidism
-Low ferritin, low serum iron, high TIBC
-IDA from increased Ferritin causes body to launch inflammatory response that prevents iron absorption
sideroblastic anemia
-Protoporphyrin synthesis defect (can’t make Heme) that is x-linked
-Ringed sideroblasts in the bone marrow
-Causes: alcohol, Vitamin b6 deficiency, lead poisoning
-Elevated iron in astores. Overload
-Iron surplus but can’t form heme (main difference form Ida)
-Confimation via bone marrow bx
acute intermittent porphyria
-Sporadic enzyme mutations in heme production-> Inc porphyrin in tissues
-Triggers: alcohol, stress, reduced caloric diet, drugs, exposure to tobacco
-s/s diffuse abdominal pain, palpitations, n/v, seizure, tingling, muscle weakness, anxiety, hallucinations, discolored urine
megaloblastic anemia
-Low Hgb, MCV >100
-Problem with DNA synthesis
-Vitamin B12 Deficiency (neuro deficit-memory loss, vision, paresthesia)
-Pernicious Anemia (loss of intrinsic factor) -> autoimmune -> doesnt let B12 across membrane (needed for RBCs)- stomach, SI, terminal ileum
-Atrophic Gastritis- H pylori infection., immune system attacks gastric cells -> B12 injections and iron infusions -> not PO bc…
-Malabsorption
-Inadequate intake- iron/vitamin B12 (vegan diet)
-Drugs blocking their absorption- chronic PPI -> decrease acidity prevent B12 absorption
-Folate Deficiency ( no neuro deficit)
-Malabsorption- primary absorption is in duodenum and jejunum
-Inadequate intake
-Increased demand- Pregnancy, liver disease
-Anti-folate drugs (phenytoin, methotrexate, sulfa drugs)
-Hypothyroidism- slow thyroid hormones suppress bone marrow
malabsorption
-Bypass can decrease absorption of food. Restrict caloric intake.
-Lack of area to absorb iron and Vitamins
-Inc chance of anastomotic ulcers-gi bleed
-Decreased intake of red meat-> decreases your iron stores.
-Can take 5 years before stores of vitamin b12 are used up
-B1- thiamine -> wernicke-korsakoff syndrome -> unsteady gait, AMS, ocular abn
polycythemia vera
-Overproduction of rBC or erythropoeitin
-Mutation in Jak2 gene-> can lead to myelofibrosis (burnt out bone marrow)
-Increased risk for blood clot, secondary to thick blood
-Treatment block JaK2-> Ruxolitinib
-Jak2-neg:
-Renal call tumor-> secreting Erythropoietin
-Conditions causing hypoxemia (OSA)
-Pumps out more RBC
myelodysplastic syndrome
-Myeloma- abn B cell-> affects the plasma cells
-Multiple myeloma- rare Plasma cell disorder, unknown cause ? Immune deficit, pesticides and ? Agent orange, viruses (HIV)
-Malignant plasma cells-> can form tumors in bone( bone reabsorbed)-> hypercalcium, bone pain ( back pain in the elderly) most common symptom. Also anemia, wt loss.
-Diagnostic-> bone marrow bx
-Tx: bone marrow stem cell transplant Age <70.
white blood cells
-Monocyte-> Macrophages-> Phagocytosis- garbage men of body
-Basophil-allergic reactions
-Eosinophil- allergy Type 1( Asthma), parasites
-Neutrophil- mini-Phagocytes, “oxidative burst”
-Platelet- Plug blood vessels
-B cell- plasma cells – help secrete antibodies (IGM, IGG)
-T Cell–> T helper cell- Help B lymphocytes make antibodies –>Cytotoxic T-cells->apoptosis of cancer cells
-Macrophages:
-Lung alveoli-phagocytosis of debri
-Kupffer cells in liver
-Splenic macrophages- eliminate old rBC
-Neutrophil- oxidative burst- absorb a bacteria convert O2 to HCL acid and burst
keeling the balance
-Under normal circumstances, there exists a fine balance between the procoagulant and anticoagulant pathway
-Procoagulant– making clots
-Anticoagulant- thinning of the blood
hemostasis
Hemostatis- mechanism that leads to the cessation of bleeding
Can be divided into 3 parts:
-Primary Hemostatsis-
-1. Constriction of blood vessel- 30 min after injury
-2. Formation of temporary platelet plug
Seconary Hemostatis-
-3. Activation of coagulation cascade-> ending with a fibrin formation (slow down blood flow making it more viscous)
-ACCOMPLISHED THROUGH THE EXTRINSIC AND INTRINSIC PATHWAYS
-Smooth muscle contraction-> endothelin leak activates the smooth muscle to contract
-Trauma to muscle it contracts-naturally
-Damaged endothelium releases VWF and platelets will plug at the site
-Failure of Primary: mucocutaneous bleeding-> no platelet plug
-Failure of secondary: deep muscle bleeding RP bleed.
coagulation cascade
-Extrinsic- ACTIVATED BY EXTERNAL TRAUMA (BLOOD ESCAPING THE VASCULAR SYSTEM)
-QUICK
-INVOLVES FACTORS VII
-Intrinsic- Activated by damage of the vessel
-Longer
-Involves Factors Factors XII, XI, IX, VIII
-Both activate Common pathway that leads to fibrin formation
-=stable fibrin clot
-you must give Ca when you transfuse blood (after 5U)
if your patient needs factors
-give FFP
-5:1:1
von willebrand ds
-MC bleeding disorder
-deficiency in VWF.
-mostly involved inprimary hemostasis. where it helps Platelets stick together. The factor also plays a role insecondary hemostasis by helping stabilize factor VIII
-LOW CIRCULATING THRYOID HORMONES CAN CAUSE AN ACQUIRED VWD
-High thyroid can encourage thrombus
-Tx : DDAVP( releases factot VIII from stores) or infuse factors
hemophilia
-caused by genetic mutations inclotting factor genes and can be passed on from parent to child.
-Hemophilia A- is a deficiency in factor VIII -> tx: plasma derived factors, recombinant factors
-Hemophilia B- is a deficiency in factor IX,
-Hemophilia C- is a deficiency in factor XI.
-All types affect the intrinsic pathway.
vitamin K deficiency
-not enough vit K absorbed from foods or when not enough foods withVit K are consumed (e.g., leafy dark green vegetables like spinach).
-Vit K a cofactor required to make factors II, VII, IX, and X functional.
-affects all three pathways
-seen in newborns, all babies get a shot at birth to prevent bleeding
-Tx: IV Vitamin K
DIC- disseminated intravascular coagulation
-Showering of clots (ischemia of multiple organs) and increase bleeding (consumption of platelets)
-Tx- stop primary cause of endothelial or tissue injury
-Replenish factors, start heparin gtt (anticoagulation)
myelocytic leukemia
-Mutation of myeloid cell, overprod of abn monocytes and granulocytes Dec in other cell types
-AML ( acute myelogenous leukemia) most common in adults, Auer rods
-CML (chronic Myelogenous leukemia) young adults, Philadelphia chromosome translocation, can transform into a blast crisis
leukocytic leukemias
-Mutation of lymphoid cell, overprod of abn immune cells, dec production in other cell types
-ALL (Acute Lymphocytic Leukemia) childhood-fatigue, epistaxis, thrombocytopenia, lymphadenopathy, bone pain, hepatosplenomegaly
-CLL ( Chronic Lymphocytic Leukemia) over 60- Smudge cells on peripheral smear
lymphoma
-Hodgkin- (AGE 20-50, M>F) Malignant B cells only invade lymphoid organs , presents as enlarged LN. (cervical is common) fatigue, wt loss, night sweats, alcohol consumption causes pain in LN!!!!!, inc incidence with AIDS
-Tx: chemo/radiation, high cure rate
-Non Hodgkin- (older) EBV?, HIV, immunosuppression can inc chances. Malignancy in B or T cell!!!!!! Can travel through the lymphatics to other organs. Presentation-dependent on site of spread. Fever, enlarged nodes, wt loss, night sweats
CBC
normal distribution of WBC
-Differential
-Never – Neutrophils 60-70% ( elevated amounts-> bacterial)
-Let –lymphocytes 20-30%. (elevated amounts-> viral)
-Monkeys- monocyte 3-8 %
-Eat –eosinophils 2-4 % (elevated amounts-> parasitic, allergic)
-Bananas- basophils 0.5-1.0 %
-LEUKOCYTOSIS- ELEVATED (MALIGNANCY(LEUKEMIA), INFECTION, INFLAMMATION(AUTOIMMUNE), DRUGS-STEROIDS, NEUPOGEN
-LEUKOPENIA- DECREASED ( CHEMO/RADIATION, SEPSIS, LYMPHOMA, BONE MARROW FAILURE
causes of thrombocytosis
-Acute- bone marrow pumps out cells
-Alcohol cessation- prolonged use and stop- use to thin blood and now cessation keeps the production high.
-Tx: primary when
thrombocytopenia
-PLT <150,000
-Conditions that cause:
-Reduced production-> bone marrow disorders, alcohol
-HIT- heparin induced thrombocytopenia -> usually a few days after
-Inc. Platelet consumption- used up platelets DIC, TTP/HUS, HIT( heparin attaches to platelets causing them to clump
-Splenomegaly- portal HTN,
-Dilutional- massive fluid rescutition
-Inc Destruction- ITP- antibodies attack platlets
-Infection-
thromboelastography
-TEG w/platelet mapping is measuring each phase of the clotting process.
-Clot initiation
-R time- first measurable clot (clotting factors) -> tx: ffp/protamine
-Clot strength- k time, angle, and MA
-K time- dependent on fibrinogen -> tx: cryoparcipitate
-Angle- rate of fibrin buildup (fibrinogen) -> tx cryo
-MA- max clot strength( depends on platelets, fibrin, Factors ->Tx: PLT/DDAVP
-LY30- Clot stability, looks at fibrinolysis tx: TXA, Amicar
-know the R and K time - deficiency
-MA- quality
