Lecture 27 - Microcytic Anemias, Porphyrias, and Hemochromatosis

Question 1

Response to acute blood loss occurs in minutes to hours and involves increased ____ rate, _______ rate, and _____ output. It also involves increase blood flow to vital organs and away from the _____ (results in pallor).

Answer 1

Heart rate

Respiratory rate

Cardiac output

Skin

Question 2

Response to slowly developing anemia occurs in days to weeks and involves an increase in the production of ,-___ (results in right shift of Oxyhemoglobin dissociation curve) and an increase in RBC production (and an increase in the appearance of ______ in the peripheral blood).

What does the Kidney produce to elicit increased RBC production?

Answer 2

2,3-BPG

Reticulocytes

Kidney produces EPO

Question 3

_______ anemias result from a decrease in the production of RBCs, while _______ anemias result from the loss of RBCs. What do you expect to happen with respect to Reticulocyte production in each case?

Answer 3

Hypoproliferative Anemias

Hemolytic Anemias

Reticulocyte production would DECREASE in hypoproliferative anemias and would INCREASE in Hemolytic Anemias.

Question 4

Microcytic anemias are classified by MCV < ____ fL. If this is found, the next thing that should be measured is serum _____. If this value is _____, then it is considered an Iron deficiency anemia. If this value is normal or high, it can be one of three disease states: 1. Anemia of chronic disease. 2. Sideroblastic anemia. 3. Thalassemias or Hb E disease/trait.

Answer 4

MCV < 80 fL

Serum Ferritin

Low –> Iron deficiency

High

Question 5

Anemia of chronic disease is characterized by what?

Answer 5

Sequestration of iron, so decreased iron availability.

Question 6

Sideroblastic anemia is characterized by deficiency or inhibition of enzymes needed to synthesize the _______ ring in the heme structure.

Answer 6

Protoporphyrin ring (protoporphyrin IX)

Question 7

Thalassemias and Hb E trait/disease are characterized by the absence or inhibition of synthesis of a _______ chain in the hemoglobin structure.

Answer 7

Polypeptide chain.

Question 8

It should make sense that Iron Deficienc Anemia (IDA) can be caused by excessive bleeding. For otherwise healthy males and post-menopausal women, where are bleeds typically suspected and what test should be performed on the stool?

Answer 8

GI bleeds are common in otherwise healthy meales and post-menopausal women. Occult blood test should be performed on the stool.

Question 9

_____ is a symptom characteristic of IDA and is defined as a craving for and consumption of unusual substances (e.g. clay, glass, dirt).

Answer 9

Pica

Question 10

_____-____ syndrome is characterized by a triad including IDA, esophageal webs, and glossitis. Because of the latter two, these patients often have _______ (Greek meaning issues with eating).

Answer 10

Plummer-Vinson

Dysphagia

Question 11

Serum _____ values are the most important in identifying IDA. Remember that it is an acute phase reactant, so its concentration will increase during inflammation. Serum Iron will decrease ONLY after storage iron is depleted. This can occur bc of infection, inflammation, and ______. Keep in mind recent ingestion of iron supps would falsely increase serum levels.

Answer 11

Ferritin

Cancer (neoplasms)

Question 12

Total Iron Binding Capacity is a measure of ______ levels. Levels will increase in IDA in response to decreased ______ (the iron storage protein). It should make sense that % ______ saturation will decrease from the normal 33% to below 16-20% in IDA, because there’s less iron available to bind (hence Iron Deficiency Anemia).

Answer 12

Transferrin (iron transport protein)

Ferritin

% Transferrin Saturation

Question 13

____cytic _____chromic RBCs are characteristic of IDA.

Answer 13

Microcytic

Hypochromic

Question 14

Anemia of Chronic Disease (ACD - it is the most common anemia in hospitalized patients) is characterized by iron maldistribution. Chronic infections, Malignancies, and Autoimmune dysregulation can lead to the production of inflammatory cytokines, particularly ____ which acts on hepatocytes to increase production of _____ (which blocks Ferroportin). Keep in mind _____ levels will be NORMAL.

Answer 14

IL-6

Hepcidin

Ferritin

Question 15

Serum Ferritin and TIBC are the two most important measures to distinguish between IDA and ACD. How do these levels compare in each case?

Answer 15

In IDA: Serum Ferritin is DECREASED and TIBC is INCREASED.

In ACD: Serum Ferritin is normal or INCREASED and TIBC is Normal or DECREASED.

Question 16

Sideroblastic Anemia arises from a defect in heme biosynthesis. Hereditary X-linked sideroblastic anemia results from a mutation in _____-2 (the first enzyme in protoporphyrin ring synth). Treatment is _____ (which vitamin?) supplementation.

Sideroblastic anemia can also be acquired from idiopathic reasons (myelodysplastic syndrome - MDS) or from drugs/toxins. _____ poisoning/toxicity leading to acquired Sideroblastic anemia is common among children because of exposure/consumption of paint chips.

Answer 16

ALAS-2

Pyridoxine (Vit B6)

Lead

Question 17

Lead poisoning inhibits _____ dehyrase and ferrochelatase in protoporphyrin synthesis. It also inhibits _____ degradation, resulting in Course ______ Stippling of RBCs. Lab results would reveal an increase in ____ (the molecule that would normally be acted on by the enzyme inhibited by Lead.) Chelation therapy includes administration of EDTA and ______.

Answer 17

ALA dehydrase

rRNA

Basophilic

ALA

Dimercaprol

Question 18

Sideroblastic anemia is characterized by an increase in Serum _____, Ring Sideroblasts (non-heme iron granules in RBC precursors), and _____ stippling (abnormal rRNA aggregates in RBCs). Non-heme aggregates in RBCs (not precursors) are termed ________ bodies. Sideroblastic Anemia can also result in iron deposition in organs.

Answer 18

Serum Ferritin

Basophilic Stippling

Pappenheimer Bodies

Look out for Basophilic Stippling and Pappenheimer bodies to distinguish between Sideroblastic Anemia and Anemia of Chronic Disease.

Question 19

Porphyria Cutanea tarda (PCT) is characterized by blistering ______ and red/brown “tea-colored” _____. This is different from Erythropoietic Protoporphyria (EPP) in that EPP is acute and manifests as Non-blistering ______. Acute Intermittent Porphyria (AIP) is characterized by polyneuropathy, abdominal pain, ______ symptoms, and ___ (color) urine.

Answer 19

Blistering Photosensitivity

Urine

Non-blistering Photosensitivity

Psychological symptoms

Red urine

Question 20

________ is defined as an Iron Overload. This typically manifests as a darkening/browning of the _____ from iron deposits. Iron deposits are mainly seen in the ____ and heart as well. This disease is usually genetic, but can be acquired –> What medical treatment might result in this? (remember chelation therapy is used in conjunction with this therapy for severe anemias and thalassemias.)

Answer 20

Hemochromatosis

Skin

Liver and Heart

Frequent transfusions might lead to acquired Hemochromatosis

Question 21

Hereditary Hemochromoatosis arises from mutations in proteins that lead to a decrease in ______ production (remember this is the protein that inhibits Ferroportin –> should make sense that this leads to an increase in Iron absorption in the intestines and movement into the blood.) Treatment is therapeutic _______ to periodically remove RBCs –> effectively decreases serum iron.

Answer 21

Hepcidin

Therapeutic Phlebotomy