Heme Exam 3

Glycoprotein

integral, account for most of the membrane sialic acid and give rbc negative charge to prevent rouleaux

Spectrin

peripheral, strengthens membrane(shape and stability) and preserves performability(pliability)

Integral

extended from outer surface through the lipid bilayer

Peripheral

line inner membrane surface to form the membrane cytoskeleton

Mechanism for producing acanthocytes

hereditary disorder of lipoprotein metabolism (abetalipoproteinemia)

Mechanism for producing bite cells

portion of rbc membrane has been removed and a permanent indentation is left in the remaining membrane

Mechanism for producing spehrocytes

reduced surface-to volume ratio, ATPase pump is too active and lose surface area because plasma membrane is not attached 

Mechanism for producing target cells

accumulation of cholesterol in RBC membrane(liver disease) increase in SA and decrease in HGB

transferrin

protein carrier that delivers iron to the RBC membrane for hemoglobin synthesis

two major tissues in the body where heme synthesis occurs

erythroid marrow(nRBCs) and liver

Chemical makeup of heme

globin(colorless) with 2 alpha and 2 non-alpha chains with 4 heme groups(color)

Why does a patient with lead poisoning present “ringed sideroblasts”

lead poisoning causes an enzyme that blocks incorporation of iron into heme molecule causing a mitochondrial buildup of iron

Why would a freshly voided urine from a patient with a porphyria may not be red

Porphyrinogen is colorless but as time goes on it will oxidize and become porphyrin and show a pinkish-red color

Relaxed form of Hemoglobin

oxyhemoglobin(arterial blood), normal HGB has affinity for oxygen which binds to iron, carriers oxygen

Tense form Hemoglobin

deoxyhemoglobin(venous blood), veins and tissues, oxygen affinity is lower resulting in unloading of oxygen by HGB

main source of ATP production in the mature RBC

glucose

metabolic pathway that generates the most of the red cells ATP

Embden-Meyerhof Pathway(2 ATP)

Embden- Meyerhof Pathway

RBC generate energy almost exclusively through the anaerobic breakdown of glucose, 90% of energy needed via anaerobic glycolysis 

Hexose monophosphate Shunt

protects RBCs from hydrogen peroxide which denatures hemoglobin, 5-10% anaerobic glucose utilization

Methemoglobin Reductase Pathway

maintains iron in the ferrous(2+) state

Leubering- Rapaport Shunt

Synthesis of 2,3 DPG(regulates O2 delivery to the tissues) 

What is the level of haptoglobin in the presence of intravascular hemolysis

decreased

Protein carrier for bilirubin

albumin

Porphyria

disorder of heme synthesis 

porphyrin

oxidized porphyrinogen, stable, fluorescent(pinkish-red) 

Porphyrinogen

precursor to porphyrin, non-fluorescent(colorless), non-stable, and quickly irreversible 

RBC indices (microcytic-hypochromic anemia)

<80 MCV and <31% MCHC

RBC indices (macrocytic anemia)

>100 MCV

RBC indices (normocytic-normochromic anemia)

80-100 MCV nd 31-36% MCHC 

reticulocyte count (aplastic anemia)

low retic count

reticulocyte count (extracorpuscular hemolytic anemia)

high retic count

anemia

a condition in which there is reduced oxygen to the tissues

dyspnea

shortness of breath or difficulty breathing

hemoglobinopathy

abnormal HGB made due to a genetic mutation in the structure od the HGb molecule 

pallor

unusual paleness of the skin, mucous membranes, or nail beds 

Thalassemia

a hereditary disorder caused by gene mutations that reduce or completely prevent the synthesis of one or more of the globin chains 

primary function of iron

oxygen transport

anatomic site for which iron is absorbed most efficiently

intestinal mucosa in the duodenum

organelle that contains iron in the erythrocyte precursor

mitochondria

serum iron

amount of iron(bound to transferrin) in the serum/plasma 

serum ferritin

equilibrium exists between intracellular ferritin and serum ferritin

TIBC

amount of iron that transferrin can bind

BM macrophage iron

iron held by RE cells in the EI that is normally used to supply the developing nRBC precursors in the BM

BM sideroblasts

nRBCs in the BM that contain iron

ZPP

when insufficient iron is available to developing nRBCs, erythrocyte protoporphyrin accumulates in the cell

Relationship between serum ferritin levels and bone marrow iron stores in a healthy individual

Serum ferritin = BM iron stores

Describe the peripheral smear RBC morphology that would prompt the ordering of iron studies

BM macrophage iron and Bm sideroblasts

Reason why long-term iron therapy should not be given to a patient with anemia of chronic inflammation (disease)

Anemia is due to impaired iron utilization caused by hepcidin, not iron deficiency, and excess supplementation risks iron overload without correcting the anemia.

Reason for the presence of "ringed sideroblasts" upon bone marrow iron exam of a patient with lead poisoning

All due to the iron overload and decreased survival of RBCs, ineffective erythropoiesis 

Characteristic RBC histogram appearance one would expect to see in a patient with sideroblastic anemia, especially a hereditary form

Ringed sideroblasts, peppenhimer bodies, basophilic stippling 

bronze diabetes

iron deposits into the organs

ferritin

protein that stores iron

hemochromatosis

disorder of iron overload characterized by increased intestinal iron

Hepcidin

a liver-produced peptide hormone that is the key regulator of iron homeostasis

ringed sideroblast

 erythroid precursor seen in BM with iron-loaded mitochondria arranged in a ring around the nucleus

sideroblast

nRBCs that contain iron

siderocyte

RBCs(non nucleated) that contain iron

Hemoglobin molecule defect found in thalassemia

Rate of synthesis of one or more of the globin chains 

suspected reasoning for the (same) geographic distribution pattern that coincide with the incidence of malaria and the heterozygous state(s) of the thalassemia syndromes.

Gene selection and being a carrier of the altered HGB gene is an advantages. It makes infections with malaria less likely (due to decreased oxygen-carrying ability) 

cooleys anemia

Beta thalassemia major

Cooleys trait

Beta Thalassemia Minor

Erythroid hyperplasia

increased production of RBC in the BM

Discuss the reason(s) why patients with Beta Thalassemia Major have the following findings: "hair-on-end" appearance on skull x-rays and Facial deformities due to skull changes 

both due to severe hemolytic anemia with strong stimulus for erythropoeisis causing an exapansion of the BM