Flashcards in Buzzwords For Heme/Lymph Final Deck (68):
This Oxidative state of Fe is required both for heme function and Fe absorption in the gut. (Where does it get absorbed?)
Fe2+ - absorbed by DMT-1 in the Duodenum
Fe3+ on Hb is Methemoglobin, which does not carry O2
What is the Committing enzyme of Heme synthesis?
Aminolevulinate Synthase (ALAS)
What is the difference between ALAS 1 and ALAS 2?
ALAS 1 is found in the liver and is subjected to feedback inhibition by heme (transcription, translation, and translocation into the mitochondria)
ALAS 2 is not inhibited by heme and is found in reticulocytes.
Name 3 things cause increased sickling?
1) Increased Deoxygenation
2) Increased HbS
3) Decreased HbF
5) Cold Temperature and infections
How do you treat those who are sickling?
1) Give suppplemental O2, fluids, and antipyretics
2) Hydroxyurea - stimulate increased HbF production
What are the two types of anemias that produce spherocytes?
What test do you use to differentiate the two?
1) Hereditary Spherocytosis
2) Autoimmune Hemolytic Anemia
Use the Coomb's (Direct Antibody Test) -
Hereditary Spherocytosis (-)
Autoimmune Hemolytic Anemia (+)
What is the Direct Coomb's test
It tests to see if there are anti-bodies DIRECTLY on the surface of RBCs.
Where would you see RBC fragments / Schistocytes
Microangiopathic Hemolytic Anemia:
1) TTP - ADAMTS13
2) HUS - E. Coli or Shiga toxin
3) H.EL.LP - High BP during pregnancy
4) Malignant HTN
5) DIC - oozing from injection site
Double Bite Cells
Splenic macrophages removing heinz bodies from RBC.
What is are Heinz Bodies
Precipitated Globins with ROS damage
Most important parameter for assessing O2 carrying capacity of the blood
What measures the "chromicity" of an RBC?
MCHC - Mean Corpuscular Hb Concentration
In acute blood loss, a CBC will often not show anemia. Why is this and when is anemia shown?
Blood loss is whole blood, anemia develops when tissue fluid enters the vascular space to restore blood volume.
Reticulocytes will increase after 2-3 days and peak at 7-10 days
Symptoms of Porphoryias with defect EARLY in the biosynthesis pathway
Neurological defects - Build up of ALA -> producing ROS
Symptoms of porphoryias with defect in the LATE biosynthesis pathway
How long after birth are Sickle Cell Symptoms usually seen? Why?
10-12 Weeks - It's the amount of time for a baby's HbF to go down. HbF is protective against HbS
What is the major cause of death in adults with Sickle Cell Disease?
Acute Chest Syndrome
Acute Chest Syndrome
Lung clots that arrise from Infection or fat emolism from infarcted marrow; the cycle goes: sluggish flow --> sickling --> vasocclusion* --> more slugish flow
In lungs hypoxia causes constriction to shunt blood away, causing more vasocclusion
Most common cause of death in Sickle cell children?
Infection! Children will die because of autoslenectomy, allowing encapsulated bacteria (Strep pneumoniae and Haemophilus influenza).
Alpastic Crisis due to a drop in RBC precursors, is typically due to this?
Where diseases do you see Aplastic Crisis?
Sickle Cell Anemia, Hereditary Spherocytosis
Percentages of Hb types in Sickle Cell TRAIT
HbA 60%, HbS 40% (If you see HbS x > 50% then there will be sickling) unless you look at the kidneys (Renal medulla) which are already hypertonic.
Thalassemia's complication are directly related to what?
Deletions (alpha thalassemias) or Mutations (Beta thalassemias) that cause a decrease or absence of globin units.
Excess normal flobin chains accumulate and cause intracellular RBC cell death (ineffective erythropoiesis) or decreased survival (hemolytic anemia)
What genetic change causes Beta Thalassemia?
Mutation (Splicing error) in the B gene on chromosome 11?
What genetic change causes Alpha Thalassemia?
Deletion of the alpha gene on chromosome 16?
What is the hall mark lab finding for Beta Thalassemia Minor?
HbA2 increases to about 5% (from 2.5%)
What is the chemical marker of hemolysis due to its binding of free hemoglobin
What does Haptoglobin bind to? What is it cleared by
Haptoglobin binds to Hb
Haptoblobin-Hb is cleared by CD 163 - a scavenger receptor on monocytes/macrophages
What happens when CD163 binds its ligand? What is its ligand?
When CD163 binds Haptoglobin-Hb it causes receptor mediated endocytosis via clatherin coated pits;
Haptoglobin is then degraded and CD163 is recycled back to the membrane
Hemolysis causes falsely HIGH or LOW lab values
When our of the RBC, Hb absorbs in the measured wavelengths
Autosplenectomy is seen in almost all adults with this condition
Sickle Cell Disease
Excess Bleeding with circumcision tips you off to what genetic bleeding disorder? What pathologies could be seen?
Hemophilia A or B (VIII or IX)
You can also see excess bleeding from the cutting of the umbilical cord.
What inheritance is Hemophilia A or B
What is the most common anemia overall?
Iron Deficiency Anemia
What is the most common Hospital patients
Anemia of Chronic disease
Heme Synthesis enzymes inhibited in lead poisoning
ALAD and Ferrochetalase.
Pb displaces Zn in ALAD, causing a build up of ALA - > Neurological defects
Why would you want to get genetic testing for Alpha Thalassemia Trait (2 deletions)?
Because you want to determine if it Cis or Trans Thalassemia
Which Haptoglobin subtype is associated with autoimmunity and disruption of HDL
Hp2-2 binds ApoA which facilitates the loss of LCAT and decreases antioxidant activity. -> Marker for coronary artery disease
Sx seen in pts. with sickle cell trait
Microhematuria and decreased ability to concentrate urine.
What binds free heme in the blood?
Hemopexin. Used when Haptoglobin is overwhelmed. Hb -> metHb + heme. hemopexin takes the free heme off of albumin. Then hemopexin-heme bind to CD91 and into macrophages.
Location of GI absorption of anemia causing substances. (Iron, Folate, Vit B12)
Iron - Duodenum
Folate - Jejunum
Vit. B12 - Iliuem
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When Fe levels are sufficient, what liver protein inhibits ferroportin? (On enterocytes and macrophages)
Blocks Fe transport into the blood via ferroportin
Suppresses EPO production
What is the most sensitive and cost effective test for iron deficiency anemia?
Low Serum Iron
Low % Saturation
Deletion of 3 alpha globin genes leads to what disease
HbH disease - B tetramers, soluble so it will not precipitate in normoblasts but will in peripheral RBC resulting in hemolysis.
Infant with Sickle Cell presents with Hb x
Why are many patients with Iron defienct or Megaloblastic anemia relatively asymptonmatic despite low Hb?
They are asymptomatic due to a physiologic compensation when deficiecy of Fe, Folate, or B12 is over a long period of time.
Symptoms of Iron Deficiency Anemia
Koilonychia (Spooning of the fingernails)
Pica - Compulsion to eat/chew on non-food (dirt/ice)
Treat Pica with Ferritin Sulfate
How long does it take for Folate stores to be depleated?
Deficiency is caused by:
1) Poor Diet
2) Increase Demand
3) Drugs - Methotrexate -> inhibits dihydrofolate reductase preventing the reuse of folate
4) Jejunal resection
Why is folate supplementation crucial in pregnancy for patients with Folate deficiency?
Without you can get neural tub defects/Anencphaly associated with deficient folate
What helps you differentiate between Folate and VitB12 deifciency
Most common cause of Vitamin B12 deficiency?
Deficient vitamin B12 secondary to decreased intrinsic factor from gastric parietal cells; MUST have an autoAb against intrinsic factor for diagnosis.
How long does it take to develop a VitB12 Deficiency
Years. Due to the massive stores in the liver.
Treatment for Beta Thalassemia Major
Transfusions with Aggressive Iron Chelation
Major = Transfusion dependent (Hb is around 2-3g/dL)
Without Aggressive Iron Chelation you would get endocrine and cardiac disease
Vitamin B12 deficiency is associated with what poor diet and what parasite
Strict vegan* diet and Diphyllobothrium latum (fish tapeworm).
*Eggs and dairy both contain vit B12 so not vegetarians; also associated with ilieal resection (site of resorption)
What three thigs require VitB12 for production
1) Tetrahydrofolate - decrease -> Impaired DNA
What is the characteristic intracellular findings and morphology (respectively) associated with G6PD Deficiency?
Heinz Bodies and Bite Cells
Heinz Bodies are precipitated Hb globins that had ROS damage. These are removed by splenic macrophages resulting in "Bite Cells"
Increased homocysteine in Megaloblastic Anemia increases risk for what complication?
Venous and Arterial Thrombosis
What genes are most commonly mutated in a patient with hereditary spherocytosis?
Anikarin, spectrin, and Band 3
Treatment for Hereditary Spherocytosis will result in the presence of what on blood smear?
You need to get a SPLENECTOMY!
A Splenectomy will result in Howell-Jolly Bodies and acanthocytes.
What two infections are associated with cold agglutinins?
Mycoplasma Pneumoniae - anti I
Infectious Mononucleosis - anti i
A patient presents with fatigue, decreased propioception on their legs, and spastic paresis. What substrate has built up and where?
Methylmalonic acid has build up in the dorsal and lateral tracts of the spinal cord causing demyelination.
A Person with pancreatic insufficiency is subjected to what type of anemia
Vitamin B12 deficient anemia.
Pancreatic enzymes cleave R-binder, which release Vit. B12 from R-binder and allows it to bind to IF in the small intestine.
Why should folate not be used to treat Vitamin B12 deficiency?
Folate will cure the anemia, but will NOT treat the neurologic symptoms
What is the essential test for diagnosis of Autoimmune hemolytic anemia?
Direct Coombs Test
What disease is most commonly associated with Warm Autoimmune Hemolytic Anemia?
What drugs are most commonly associated with Warm Autoimmune Hemolytic Anemia?
Methyldopa & Penicillin/Cephalosporin
Penicillin causes a response while bound to the RBC while methyldopa causes generation of AB against RBCs
A patient presents with acrocyanosis, Raynaud's phenomenon, and anemia, what isotype of AB is elevated in their blood?
Agglutination exasperated with cold exposure. Hemolysis due to COMPLEMENT!