Anemia

Question 1

What is the life span of a normal RBC?

The bone marrow is stimulated to make red cells by the hormone ___ which comes from the kidneys

Answer 1

120 days bruh

Erythropoietin

Question 2

___ is a molecule that promotes O2 unloading from the RBCs and stabilizes the deoxy form of hemoglobin

Answer 2

2,3-Diphosphoglycerate

Question 3

What is the difference between hematocrit and MCV?

Answer 3

Hematocrit: Ratio of packed red cell volume to total blood volume

Mean corpuscular volume: Average volume of a red cell (Hematocrit/number of red cells)

Question 4

Define anemia

Answer 4

Low red cell mass/red cell mass below 13.5g/dl in men and 12.5g/dl in women

Question 5

What features of a person’s history might clue you into anemia?

What are the features on the physical exam might suggest anemia?

Answer 5

Weakness/fatigue, dyspnea upon exertion

Pale conjunctiva (in darker skinned pts)

Pallor

Tachycardia

Question 6

When anemia is severe, the patient may begin to experience hypoxia. Besides headaches and dim vision, the patient may also experience ___ (due to ischemic cardiac muscle) and ___ (due to ischemic skeletal muscle)

Answer 6

When anemia is severe, the patient may begin to experience hypoxia. Besides headaches and dim vision, the patient may also experience angina (due to ischemic cardiac muscle) and claudication (due to ischemic skeletal muscle)

Question 7

In the case of anemia, the body compensates for the low RBC state in various ways, including increased __ in the lungs, __ CO, PR and blood flow.

___ goes up to promoteO2 unloading in the tissues.

In the peripheral organs, __ decreases to help with O2 extraction. They also undergo ___, and in the kidney, ___ is released to promote eryhtropoiesis

Answer 7

In the case of anemia, the body compensates for the low RBC state in various ways, including increased RR in the lungs, inreased CO, PR and blood flow from the heart

2,3 DPG goes up to promote O2 unloading in the tissues.

In the peripheral organs, pH decreases to help with O2 extraction. They also undergo vasodilation, and in the kidney, erythropoietin is released to promote erythroopoiesis

Question 8

Based on MCV, how would you classify normal vs microcytic vs macrocytic anemia?

Answer 8

Normocytic anemia – normal MCV

Microcytic anemia –smaller MCV

Macrocytic anemia – higher MCV

Question 9

In microcytic anemia, the cells are smaller because ___, where as in macrocytic anemia, there is a defect in ___, resulting in arrest in mitosis and non-dividing cell growth, leading to larger cells

Answer 9

In microcytic anemia, the cells are smaller because they have less hemoglobin in them, where as in macrocytic anemia, there is a defect in DNA synthesis, resulting in arrest in mitosis and non-dividing cell growth, leading to larger cells

Question 10

Two of the causes of normocytic anemia include ___ and ___ (subtype of anemia)

Answer 10

Two of the causes of normocytic anemia include blood loss and hemolytic anemia (subtype of anemia)

Question 11

Four causes of microcytic anemia include __ deficiency anemia, anemia of chronic disease, sideroblastic anemia and ___

Answer 11

Four causes of microcytic anemia include Fe deficiency anemia, anemia of chronic disease, sideroblastic anemia and thalassemia

Question 12

___ anemia is an issue with the poryphyrin ring in Hb (hint: you don’t value your “ring” i.e. marriage anymore so you go and find a side piece)

Answer 12

Sideroblastic anemia is an issue with the poryphyrin ring in Hb (hint: you don’t value your “ring” i.e. marriage anymore so you go and find a side piece)

Question 13

Macrocytic anemia can be divided into ___ and ___

Answer 13

Macrocytic anemia can be divided into megaloblastic and non-megaloblastic anemia

Question 14

___ and ___ deficiencies can cause megaloblastic anemia

___ and ___ can cause non-megaloblastic anemia

Answer 14

Vitamin B12 and Folate deficiencies can cause megaloblastic anemia

Liver disease and drugs can cause non-megaloblastic anemia

Question 15

The most worrisome issue with acute blood loss is ___, which can lead o cardiac collapse, shock and death so you want to perfuse the patient first.

Treatment of acute blood loss involves perfusion with ___ such as __ and __, +/- RBCs, depending on degree of blood loss

Answer 15

The most worrisome issue with acute blood loss is hypovolemia, which can lead to cardiac collapse, shock and death so you want to perfuse the patient first.

Treatment of acute blood loss involves perfusion with acellular fluids such as electrolyte solutions and colloids (e.g. albimun + dextran), +/- RBCs, depending on degree of blood loss

Question 16

Chronic anemia can result from __ or __ or RBCS

2 things that can help establish chronic anemia are a change in ___ and the presence of ___

Answer 16

Chronic anemia can result from destruction or impaired production of RBCS

2 things that can help establish chronic anemia are a change in MCV and the presence of reticulocytes

Question 17

Draw and describe the chart that explains how to come up with a differential for the anemias

Answer 17

Question 18

There are 2 ways that hemolysis can occur, namely ___ and ___.

___ occurs when the RBCs are destroyed w/in the the reticuloendothelial system, esp the spleen

___ occurs when the rbcs are destoyed w/in blood vessels and can be fatal if it occurs rapidly

Answer 18

There are 2 ways that hemolysis can occur, namely extravascular and intravascular hemolysis.

Extravascular occurs when the RBCs are destroyed w/in the the reticuloendothelial system, esp the spleen

Intravascular occurs when the rbcs are destoyed w/in blood vessels and can be fatal if it occurs rapidly

Question 19

Extravascular hemolysis can lead to some ailments, namely unconjugated bilirubin jaundice, ___ and ___

Draw the chart that shows extravscular hemolysis

Answer 19

Extravascular hemolysis can lead to some ailments, namely unconjugated bilirubin jaundice, bilirubin stones and splenomegaly

Question 20

In intravscular hemolysis, you would expect to see reduced serum ___ (molecule that binds Hb in blood vessels), hemoglobinemia and ___

Answer 20

In intravscular hemolysis, you would expect to see reduced serum haptoglobin (molecule that binds Hb in blood vessels), hemoglobinemia and hemoglobinuria

Question 21

The features of hemolytic anemia include increased ___ levels (compensatory mechanism), lower RBC lifespan and ___

Answer 21

The features of hemolytic anemia include increased erythropoietin levels (compensatory mechanism), lower RBC lifespan and accumulation of RBC

Question 22

For inherited causes of hemolytic anemia, the 3 umbrella categories are membrane defects, __ and ___ defects

Give an example of each defect

Paroxysmal Nocturnal Hemoglobinuria is an example of ___

Answer 22

For inherited causes of hemolytic anemia, the 3 umbrella categories are membrane defects, enzyme defects and globin defects

Membrane defect: hereditary spherocytois & elliptocytosis

Enzyme defect: G6PD deficiency

Globin defect: Sickle cell anemia

Paroxysmal Nocturnal Hemoglobinuria is an example of an acquired genetic defect

Question 23

____ is a disorder caused by mutations leading to inadequate membrane cytockeletal components (membrane to be unstable so its more prone to hemolysis)

In a blood smear, the cells would look like ___instead of biconcave shape

The mutated proteins include mutations in band 3, ___, ___ or spectrin

Answer 23

Hereditary spherocytosis is a disorder caused by mutations leading to inadequate membrane cytoskeletal components (membrane to be unstable so its more prone to hemolysis)

In a blood smear, the cells would look like spheres instead of biconcave shape

The mutated proteins include mutations in band 3, ankyrin, band 4.2 or spectrin

Question 24

Hereditary elliptocystosis is caused by __

Answer 24

Hereditary elliptocystosis is caused by mutations that destabilize the cytoskeleton (cells look like cigars)

Question 25

Herediatry spherocytosis is often ass’d with ___ infection, which suppresses marrow, which then affects all cells and causes increased risk for aplastic anemia

Answer 25

Herediatry spherocytosis is often ass’d with parvovirus infection, which suppresses marrow, which then affects all cells and causes increased risk for aplastic anemia

Question 26

Describe the osmotic fragility test and the results you would expect to see between normal RBCs and those in hereditary spherocytosis

How would you treat this disorder?

Answer 26

(see image below)

Treatment: folate (b/c high red cell turnover) or splenectomy

Question 27

____ is the enzyme involved in preventing oxidative damage and in normal pts, levels of this enzyme drop but in pts with this deficiency, the drop occurs earlier

Answer 27

G6PD is the enzyme involved in preventing oxidative damage and in normal pts, levels of this enzyme drop but in pts with this deficiency, the drop occurs earlier

Question 28

G6PD deficiency can lead to what type(s) of hemolysis?

A characteristic type of RBC you’ll see in a peripheral smear of G6PD deficiency is a ___ cell, which forms due to what process?

Answer 28

Both intravascular and extravascular hemolysis

A characteristic type of RBC you’ll see in a peripheral smear of G6PD deficiency is a bite cell, which forms because Hb precipitates into Heinz bodies which are bitten off by circulating macrophages

Question 29

Why does testing for G6PD deficiency following an acute hemolytic episode reflect normal enzyme levels?

Answer 29

When you test right after an acute hemolytic episode, it’ll look normal coz only young rbcs are left behind so the recommendation is 6 weeks following crisis

Question 30

Paroxysmla nocturnal hemoglobinuria is the only acquired genetic defect resulting in hemolytic anemia. It arises due to___

Answer 30

Paroxysmal nocturnal hemoglobinuria is the only acquired genetic defect resulting in hemolytic anemia. It arises due to a mutation in membrane anchor protein (phosphatidylinositol glycan complementation group A gene (PIGA)) leading to increased hemolysis

Question 31

Why do patients with PNH also present with leukopenia and thrombocytopenia in addition to anemia?

Answer 31

The causative mutation occurs in a hematopoietic stem cell, all the blood cells are deficient in GPI-linked membrane proteins

Question 32

The most common cause of death for PNH patients is ___ due to ___

Diagnosis of PNH is based on flow cytometry and pts are deficient in which 3 GPI linked proteins that regulate complement?

Answer 32

The most common cause of death for PNH patients is thrombosis due to platelet dysfunction

CD55

CD59 (inhbits C3 convertase >> prevents activation of alternative complement pathway >> pts have increased susceptibility to complement-mediated hemolysis b/c of the deficiency)

C8 binding protein

Question 33

24 year old woman is pregnant for the first time. She is found to be O+ (blood group O, rhesus D+). Her spouse if O- (blood group O, rhesus D-). What is the risk to current and future pregnancies with no interventions?

A.No risk to current or future fetuses.

B.No risk to current fetus. Mom may form anti-D antibodies now that will cause fetal hemolytic anemia during subsequent pregnancies

C.No risk to current fetus. Mom may form anti-D antibodies now that will cause maternal hemolytic anemia during subsequent pregnancies

Answer 33

A.No risk to current or future fetuses.

Question 34

Describe a case of Rh hemolytic disease of the newborn

Answer 34

An Rh(-) mother is exposed to D antigen when she has her first baby (who’s Rh+). By the time she has the 2nd one, she’s made anti-D antibodies that can cross over to baby # 2 and cause severe hemolysis

(baby # 2 can be born w/ jaundice and hydrops fetalis; treatment = anti-D IgG)

Question 35

Describe a case of ABO hemolytic disease of the newborn

Answer 35

A type O mom has a baby that’s A or B and her anti A or anti B antibodies cross over to the baby and cause MILD hemolysis which manifests as jaundice

Mild jaundice can be treated w/ phototherapy, severe jaundice w/ exchange transfusion

Question 36

Two examples of antibody mediated hemolytic anemia are ___ and ___

Answer 36

Two examples of antibody mediated hemolytic anemia are Rh hemolytic disease of the newborn and ABO hemolytic disease of the newborn

Question 37

Examples of scenarios that can cause mechanically induced hemolytic anemia include running marathons, heart valve problems, ___, ___ and ___

Answer 37

Examples of scenarios that can cause mechanically induced hemolytic anemia include running marathons (marathon hemoglobinuria, (mechanical/infected) heart valves, burns, hemodialysis and microangiopathic hemolytic anemia (shearing of cells by platelet thrombi)

Question 38

Examples of infections that can lead to hemolytic anemia include ___ (this was your job 4 2 years), (something about a babe), Bartonellosis and ___

Answer 38

Examples of infections that can lead to hemolytic anemia include malaria, babesiosis, bartonellosis and clostridium perfringens

Question 39

What are the patterns of fever for the 4 most common malaria parasites?

Answer 39

Plasmodium vivax/ovale – Tertian fever (q48 hr)

Plasmodium malariae – quartan fever (q72 hr)

Plasmodium falciparum – Severe, irregular fever patterns

Question 40

How can you tell a case of babesiosis from malaria on a peripheral blood smear?

Answer 40

Babesiosis wil have a tetrad form of ring parasites (aka the maltese cross)

Question 41

Which of the following is likely NOT a cause of hemolytic anemia?

A.Transfusion of type O+Rh- blood to type A Rh+ patient

B.Transfusion of type A+Rh- blood to type B Rh+ patient

C.Patient with mechanical heart valve

D.Plasmodium falciparum infection

E.Bongo drummer at a 7 day music festival

Answer 41

Transfusion of type O+ Rh- blood to type A Rh+ patient

Question 42

How is iron deficiency anemia different from anemia of chronic disease?

Describe sideroblastic anemia

Answer 42

Iron deficiency anemia is a lack of iron whereas anemia of chronic disease involves iron being unavailable to developing cells (coz the person’s been sick for so long)

Sideroblastic anemia involves iron being trapped in mtoc of developing cells

Question 43

What are some of the clinical manifestations of iron deficiency?

Answer 43

Pica**

Angular stomatitis

Koilonychia

Anemia symptoms

Stunted growth + impaired cognitive development in kids; increased risk of preterm birth/low birth weight in expecting moms

Question 44

In the iron cycle, what are the roles of transferrin, hepcidin and ferritin?

In which blood cells is iron stored?

Answer 44

Transferrin - circulating in the blood; picks up Fe and transports it to the liver

Ferritin - sequesters iron and stores it

hepcidin - inhibits iron absorption and transferrin activity

Marrow erythroid precursors and mononuclear phagocytic cells

Question 45

What do you expect to happen with the following lab values in iron deficiency anemia?

serum iron

TIBC (total iron binding capacity aka transferrin)

% transferrin saturation

ferritin

free erythrocyte protoporphyrin

Answer 45

serum iron - decreases

TIBC (total iron binding capacity aka transferrin) - increases

% transferrin saturation - decreases

ferritin - decreases** (except in an inflammatory state, in which case the levels will go up b/c its an acute phase reactant)

free erythrocyte protoporphyrin - increases

Question 46

What induces anemia of chronic disease and what are the downstream effects?

Answer 46

CD4+ T cell release of IL6, which induces hepcidin >> blocked iron release from macrophages + gut iron absorption

Also, cytokine mediated inhibition of erythropoiesis

Question 47

What would be the levels of the following in anemia of chronic disease vs iron deficiency anemia?

IL6

Transferrin

Ferritin

Answer 47

Anemia of chronic disease: transferrin = low to normal; IL6 = high; ferritin = normal to high

Iron deficiency anemia: transferrin = high; IL6 = normal; ferritin = low

Question 48

The x-linked form of Sideroblastic anemia results from a deficiency in the ___ enzyme, resulting in iron entrapment in the mitochondria

Answer 48

The x-linked form of Sideroblastic anemia results from a deficiency in the ALA synthase enzyme, resulting in iron entrapment in the mitochondria

Question 49

What are the morphologica features of sideroblastic anemia on a peripheral blood smear?

Answer 49

Dimorphic RBCs (some big some small)

Pappenheimer bodies in the red cells

Question 50

___ will be increased in folate deficiency, whereas both ___ and ___ will be increased in B12 deficiency

Answer 50

Homocysteine will be increased in folate deficiency, whereas both homocysteine and methyl malonate will be increased in B12 deficiency

Question 51

Draw and explain the absorption of B12 in the body. What are the roles of the following:

R binders

Intrinsic factor

Transcobalamins I-III

Answer 51

R binders: bind B12 in stomach (but they exist in the saliva)

IF: complexes w/ B12 in the terminal ileum

Transcobalamins: carry absored B12 to the blood stream (esp II, required for transfer to tissues)

(see image below for drawing)

Question 52

Pernicious anemia results from a deficiency in ___, which is necessary for B12 absorption. How does this deficiency arise?

Answer 52

Pernicious anemia results from a deficiency in intrinsic factor, which is necessary for B12 absorption

Parietal cells are destroyed by auto immune antibodies so they won’t make intrinsic factor

Question 53

Describe the Schilling test for B12 deficiency

Answer 53

Patient is given excess, oral radioactive B12. If absorbed, some of it will leave in the urine, and if not, it’ll be found in the feces

Question 54

What particular symptom in a patient’s history will clue you into B12 deficiency and not anemia?

Answer 54

Neurological deficits: loss of sensation