Block 4: Anemia Med Chem Flashcards
What is hematopoiesis?
Continual replacement of mature blood cells
What nutrients are required for hematopoiesis?
Iron, Vitamin B12, folic acid
What growth factor increases hematopoiesis?
Erythropoeitin
What gives rise to all types of blood cells?
Pluripotent stem cells
What is anemia?
A deficiency of RBC or Hg
What factors does a CBC test measure?
- Number of RBC
- Number of WBC
- Total amount to Hg
- Hematocrit
What is hematocrit?
Total fraction of blood that is made up of RBC and its size
T/F Anemia is a disease.
An indication of a disease process/alteration in body function
What are the outcomes of prolonged anemia?
- Tissue hypoxia
- Physical fatigue
- Angina
- Cramps
- DZ
How does CV system compensate for anemia?
- Increased CO
- Tachycardia
- Vasoconstriction and dilation
- Complications in patients with CV disease
What are the causes of anemia?
- RBC loss w/o destruction
- Deficient RBC porduction
- Increased RBC destruction over production
In what ways can RBC loss w/o RBC destruction?
- Hemorrhage
- Menstrual flow
- Gynecological disorders
- Pregnancy
- Parasites (hook worm)
In what ways can there be a deficiency in RBC production?
- Neoplasia
- Myelofibris
- Pernicious anemia
- Iron deficiency anemia
- Aplastic anemia
- Renal disease (Increased RBC destruction over erythropoiesis)
What is are some of the causes of hemorrhages?
- Trauma
- Surgery
- Disorders: cancer, ulcers, TB, DVD, IBS
What is neoplasia?
- Leukemia
- Metastasis to bone marrow
- Osteogenic sarcoma
What is pernicious anemia?
Caused by a lack of intrinsic factor, a substance needed to absorb Vit B12 from the GIT
What is aplastic anemia?
Bone marrow doesn’t produce enough or any new cells to replenish the blood cells
In what ways can there be increased RBC destruction over production?
Intrinsic and extrinsic abnormalities
What are intrinsic abnormalities?
- Thalassemia
- G6PD- glucose-6-phosphate dehydrogenase defficiency
- Sickle cell anemia
- Hereditary sperocytosis
What are extrinsic abnormalities?
- Infections (malaria, mycoplasma)
- Lead poisoning
- Disseminated intravascular coagulation
What is thalassemia?
Genetic defect results in reduced rate of synthesis of normal global chains
What is sickle cell anemia?
RBC that contain mostly hemoglobin S, difficulty passing through small capillaries and die faster
What is hereditary sperocytosis?
Defective RBC membrane (smaller, spherical, fragile)
How do you treat myelosupression?
EPO
How do you treat microcytic, macro, pernicious anemia?
- Iron
- Vitamin B12
- Folic Acid
How do you treat hemolytic anemia?
Steroids (methylprednisolone)
Rituximab
How do you treat sickle cell?
- Hydroxyurea, Oxbryta
- Crizanlibumab, L-Glutamine
What is this?
Normal RBC: 1/3 central pallor
What is the common cause for Hypochromic Microcytic Anemia?
Iron deficiency (lack of nutrition)
What is this?
Hypochromic Microcytic Anemia: RBC are smaller with increased central pallor
What are the functions of iron?
- O2 transport (Hg)
- Heme enzymes
- Metalloflavoprotein enzymes
- The mitochondrial enzyme alpha-glycerophosphate oxidase and other mitochondrial enzymes
- Immune function
- Brain function
Identify the components?
What is the the difference between ferrous and ferric?
Ferrous: Better oral absorbtion
Ferric: Better IV
What are the salts of ferrous?
Sulphate (Slow Fe and Slow Fe + Folic acid)
Gluconate (Fergon)
Fumarate (Iron)
What are the ADRs of PO iron?
- Nausea
- Gastric discomfort
- Contipation
- Diarrhea
How do you avoid side effects when using PO Iron?
Start patients on small doses and increase gradually
What is INFeD?
Liquid complex of ferric hydroxide and dextran for IV or IM use
What are are the components of INFeD?
- Iron dextran
- Sodium ferric gluconate
- Iron Sucrose
- Ferumoxytol
- Ferric carboxymaltose
ADRs of using INFeD?
Anaphylactic shock
What are the uses of parenteral iron? Down sides?
- Renal failure
- Short bowel
- Celiac disease
Doesn’t necessarily provide a faster response than PO
What is this?
Megaloblastic (Macrocytic) Anemia: RBC are large as WBC, fewer RBCs
What causes Megaloblastic anemia?
Lack of Vit B12 (cyanocobalamin) or folic acid
Why is Megaloblastic anemia problematic?
- Lack of B12 and folic → prevents DNA and RBC production
- Macrolytic cells may have enough Hb but are not concave
- Can’t transport O2
- Cells damage more easily
Why is B12 and folic acid important?
- Helps with DNA synthesis
What are symptoms of B12 and folic acid deficiency?
- Megaloblastic anemia, abnormal macrocytic RBCs, severe anemia
- B12 def → neurological symptoms
How is B12 synthesized?
Basic structure is from bacteria, fungi, and algae, but conversion takes place in the body
Is cyanocobalmin a nature product?
Used as a supplement and additive due to its stability → converted by biochem reactions
What is another name for B12?
Extrinsic factor
What is the function of extrinsic factor?
Combined with intrinsic factor produced but the parietal glands of the stomach
Combo enables binding to receptor and phagocytosis of the complex by the distal ileum cells
What is an example of vitamin B12 def caused by autoimmunity?
Inability to absorb due to destruction of parietal cells of the stomach
What are the causes of pernicious anemia?
- Defective secretion of intrinsic factors
2.Gastrectomy - Damaged distal ileum (IBD/IBS)
- Chronic pancreatitis, thyroid disease, bacterial overgrowth in SI
What are the symptoms of B12 def?
- Diarrhea
- Loss of appetite
- Weight loss
- Weakness
- Sore tongue
- HA
- Heart palp
- Irritability
- Behavioral disorders
How does B12 def present differently in adults and children?
Adults: anemia
Infants: slow growth rate
What can replace B12?
Folic acid
What is the function of folic acid?
- Serve as an acceptor and donor of single carbon units in reactions requiring one-carbon transfer
- Responsible for all oxidation levels of carbon except CO2 where biotin is the carrier
- Important for the synthesis of thyamine
What is the active coenzyme for of folic acid?
tetrahydrofolate (THF): 2 successive reductions of folate by dihydrofolate reductase
Describe the R groups of folate molecules?
1-7 glutamate units bound in g-carboxyl amide linkages
Describe the conversion of folate to THF?
Describe methyl transfer with folate?
When would the synthesis of DNA bases be rapid and fast?
- Developmental stages of pregnancy (NTDs)
- Formation of new blood cells
What is dUMP? How is it synthesized?
B12 substrate necessary for DNA synthesis and cell division
DTMP → dUMP
What are the presentations of autoimmune hemolytic anemia?
- Mixed thermal range of autoantibodies
Autoantibodies that target self RBC
What is the treatment for AIHA?
- CCS
- Rituximab +/- splenectomy (2nd line when steroid fails or relapse occurs)
What is Rituximab?
Chimeric monoclonal antibody against CD20 protein of B cells surface → Binds to CD20 → triggers cell death
What is hemoglobin S?
RBC substitution of glutamic acid with valine at the 6th residue of the beta chain subunit of Hg
What happens to HbS during low O2?
HbS aggregates and distorts into a sickle shape → cells become rigid, fragile, lose O2 carrying capacity
What occurs during Vaso-occulusive crisis?
Endothelium activated recruits leukocytes → E-selectin/P-selectin on endothelium generate signals activating MAC1→ Crawling macrophage captures normal and sickle cell RBCs
What are the ScA treatments?
- Hydroxyurea
- Voxelotor (Oxybryta)
- Crizanilzumab (Adakveo)
- L-glutamine
What is the MOA of hydroxyurea?
- In ScA, HU induces an upregulation in the concentration of fetal hemoglobin through an imprecise mechanism.
- Fetal hemoglobin does not polymerize or deform like HbS
What is the MOA of Voxelotor?
Binds to deoxygenated HbS to lessen polymerization and increase oxygen affinity
What is the MOA of crizanliumab?
Targets P-selectin blocking it’s interaction with RBC, platelets, WBCs, and endothelial cells
What is L-glutmaine?
SS RBCs have ↑ levels of ROS → PO L-glutamine ↑ NAD redox potential and NADH level in sickle RBCs → Less damage, deformation, adhesion, decreased VOC
What is the dose of L-glutamine?
0.3g/kg
10-30g/day
