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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
4) Acidosis
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:
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

G6PD Deficiency

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

Hemoglobin Concentration


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?

Parvovirus B19


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

Falsely High

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

I'D /Fight Justin /Beiber Instantly


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?

Serum Ferritin

Low Ferritin
High RDW
High FEP
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

Splenic Sequestration


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

Methymalonic Acid


Most common cause of Vitamin B12 deficiency?

Pernicious Anemia.
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
2) Methionine
3) Succinyl-CoA


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!


In G6PDH Deficiency, protection from oxidative stress is lacking because no _____ is produced so __________ is not made

In G6PDH Deficiency, protection from oxidative stress is lacking because no NADPH is produced so Glutathione is not made