Pathoma: Chapter Five

Front 1

What is anemia?

Back 1

Reduction in circulating RBC MASS!

Front 2

Sx of Anemia? 6

Back 2

Signs of Hypoxia
1. Weakness
2. Fatigue
3. Dyspnea
4. Pale conjunctiva and skin
5. HA
6. Angina, esp with previous heart problems

Front 3

What are the values of anemia in males and females?

Back 3

Male (13.5 - 17.5 g/dL) Anemia = <13.5

Female (12.5 - 16) Anemia = <12.5

Front 4

How are anemias classified?

Back 4

Mean Corpuscular Volume (MCV) - Size of RBC, correlates to the amount of divisions of the Erythroblast

1. Microcytic <80

2. normocystic 80-100

3. macrocystic >100

Front 5

How is a microcystic anemia produced?

Back 5

-dec production of hemoglobin

RBC progenitor cells in the bone marrow are normally large and divide multiple times, microcystic anemia is due to an "extra" division to try to maintain hemoglobulin concentrations

Front 6

What makes up Hemoglobin? How does it relate to microcytic anemias.

Back 6

Hemoglobin = Heme + globin

Heme = Fe + protoporphyrin

Globin

A dec in any of these could lead to microcytic anemias.

Front 7

Causes of Microcytic Anemias?

Back 7

1. Iron deficiency
2. Anemia of Chronic Disease
3. Sideroblastic anemia
4. Thalassemia

Front 8

What is the most common form of anemia and how does it develop?

Back 8

Iron deficiency

Dec iron => dec heme => dec hemoglobin => microcytic anemia

Front 9

What transports iron in the blood and delivers it to the liver and bone marrow macrophages for storage?

Back 9

Transferrin

Front 10

Enterocytes transports iron across the cell membrane into blood via?

Back 10

ferroportin

Front 11

Stored intracellular iron is bound to ?? why?

Back 11

ferritin - prevents iron from forming free radicals via Fenton reaction

Front 12

What is TIBC?

Back 12

Total iron binding capacity - measure of transferrin molecules in the blood (receptors available to bind)

Front 13

What does % saturation refer to in iron?

Back 13

percentage of transferrin molecules that are bound by iron
normal = 33%

Front 14

What does the serum ferritin tell you?

Back 14

the iron stores in macrophages and the liver

Front 15

What are five common instances in certain age groups which dietary iron can be deficient?

Back 15

1. infants - breast feeding, boobie milk is low iron
2. children w/ poor diets
3. Adults - peptic ulcers, menorrhagia, or pregnancy
4. Elderly - carcinoma in western world or hookworm (Ancylostoma or Necater)
5. Gastrectomy or malnutrition

Front 16

Stages of iron deficiency? 4

Back 16

1. Storage is depleted = dec ferritin and inc TIBC (more receptors available to bind)

2. Serum iron is depleted = dec serum iron and dec % saturation

3. Normocytic anemia - BM makes fewer but normal sized RBCs

4. Microcytic, hypochromic anemia = BM makes smaller and fewer RBCs

Front 17

Clinical sx of microcytic anemia? 3

Back 17

1. Anemia
2. Koilonychia - spoon shaped nails
3. Pica

Front 18

Pt presents with beefy red tongue, anemia, and dysphagia. What do they have?

Back 18

Plummer-Vinson syndrome = iron deficiency anemia with esophageal webs

Front 19

What is the progression of anemia of chronic disease?

Back 19

1. Chronic disease results in production of acute phase reactants in the liver like hepcidin

2. Hepcidin sequesters iron in storage site by limiting iron transfer from macrophages to erythroid precursors and suppressing erythropoietin

Front 20

Lab findings of Chronic disease microcytic anemia? 5

Back 20

1. inc ferritin
2. dec TIBC
3. dec serum iron
4. dec saturation
5. inc free erythrocyte protoporphyrin

Front 21

What happens in sideroblastic anemia?

Back 21

defective protoprophyrin synthesis
dec proto => dec heme => dec HB => microcytic anemia

Front 22

What is used in protoporphyrin production?

Back 22

Vitamin B6

Front 23

What happens if protoporphyrin is deficient?

Back 23

iron remains trapped in the mitochondria and forms a ring around the nuc of erythroid precursors "ringed sideroblasts"

Front 24

Rate limiting enzyme in protoporphyrin production and most common congenital defect in sideroblastic anemia?

Back 24

ALAS = aminolevulinic acid synthesized

Front 25

What are some acquired causes of sideroblastic anemia?

Back 25

1. Alcoholism => mitochondrial poison
2. Lead poisoning => inhibits ALAD and ferrochelatase
3. Vitamin B6 deficiency => cofactor for ALAS ( side effect for isoniazid tx of TB)

Front 26

LABS
inc ferritin
dec TIBC
inc serum iron
inc saturation

Back 26

SIDEROBLASTIC ANEMIA
- iron-overloaded state b/c mitochondria die and trapped iron leaks out

Front 27

What is thalassemia? What's an inherited perk?

Back 27

anemia due to dec synthesis of the globin chains of hemoglobin

dec globin => dec hemoglobin => microcytic anemia

- carriers are protected against Plasmodium falciparum

Front 28

What are 3 normal types of hemoglobin?

Back 28

HbF = alpha 2 y2

HbA = alpha 2 beta 2

HbA2 = alpha 2 delta 2

Front 29

Alpha Thalassemia is usually do to what? What are the four types?

Back 29

gene deletion; 4 alpha genes are presnt on chromosome 16

1. One gene deleted = asymptomatic

2. Two genes = mild anemia with inc RBC; cis deletion could inc risk in offspring

3. Three genes = severe anemia where Beta chains form tetramers that damage RBCs (HbH)

4. Four genes deleted = lethal in utero (hydrops fetalis); y chains form tetramers (Hb Barts) that damage RBCs

Front 30

What is the difference between cis and trans deletions when two genes are deleted in alpha thalassemia?

Back 30

Cis = deletions occur on the same chromosome; seen in Asians

Trans = one deletion on each chromosome; African Americans usually

Front 31

What is seen on electrophoresis?

Back 31

1. Beta chains form tetramers that damage RBCs = HbH is seen

2. Four genes deleted; y chains form tetramers (Hb Barts) that damge RBCs; Hb Barts are seen on electrophoresis

Front 32

What are Beta Thalassemias usually due to and who do they commonly occur in?

Back 32

Gene mutations

- African and Mediterranean
- Two Beta genes are present on chromosome 11; mutations result in absent or diminished production of the Beta globin chain

Front 33

What is Beta Thalassemia minor?
What is seen on blood smear?

Back 33

- mildest form of the disease and is usually asymptomatic with an inc RBC count

- Microcytic, hypochromic RBCs and target cell are seen on blood smear

Front 34

What is Beta Thalassemia major?

Back 34

- the most severe form presents with severe anemia a few mos after birth

- tetramers aggregate and damage RBCs resulting in ineffective erythropoisis and extravascular hemolysis

- chronic transfusion are often necessary

Front 35

Massive erythroid hyperplasia ensues from Beta Thalassemia major resulting in ... 3

Back 35

1. expansion of hemotopoisis into the skull (reactive bone formation leads to crewcut on xray)

2. extramedullary hematopoisis with hepatosplenomegaly

3. Risk of aplastic crisis with parvovirus B19

Front 36

What does a blood smear for Beta Thalassemia major show?

Back 36

microcytic, hypochromic RBCs with target cells and nucleated RBCs

Front 37

What are the two most common causes of Macrocytic anemia?What are 3 other causes?

Back 37

MCV > 100 due to folate or B12 deficiency (megaloblastic anemia)
1. Alcohol
2. Drugs
3. Liver disease

Front 38

How are folate and Vitamin B 12 necessary for synthesis of DNA?

Back 38

1. Folate circulates as methyltetrahydrofolate (methyl THF) and removing the methyl allows for participation in DNA synthesis

2. Methyl is transferred to Vitamin B12 Cobalamin

3. Vitamin B12 then transfers it to homocysteine, producing methionine

Front 39

Lack of folate or vitamin B12 impairs synthesis of DNA precursors leading to what?

Back 39

impaired division and enlargement of RBC precursors leads to megaloblastic anemia

impaired divison of granulocytic precursors leads to hypersegmented neutrophils >5 lobes

Front 40

Lab findings:
1. Macrocytic RBCs and hypersegemented neutrophils
2. Glossitis from dec turnover
3. dec serum folate
4. inc serum homocysteine
5. normal methylmalonic acid

What is this?

Back 40

Folate deficiency - absorbed in jejunum, within months
- poor nutrition: alcoholics
- inc demand: pregnancy, cancer
- folate antagonists

Front 41

How is Vitamin B12 absorbed? How long until depleted?

Back 41

1. Liberated by amylase in saliva
2. Then bound by R-binder and carried through stomach
3. Pancreatic proteases in the duodenum detach vitamin B12 from R-binder
4. Vitamin B12 binds to intrinsic factor (made by parietal cells)
5. Absorbed in ileum

Takes yrs to deplete.

Front 42

What is the most common cause of Vitamin B12 ?

Back 42

Pernicious anemia - Autoimmune destruction of parietal cell leading to intrinsic factor deficiency (which absorbed Vitamin B12)

Front 43

Crohns disease
Diphyllobothrium latum - the fish tapeworm
Vegans

These ppl could all be deficient in what?

Back 43

Vitamin B12

Front 44

Lab Findings: what is it?
1. Macrocytic RBCs with hypersegmented neutrophils
2. Glossitis
3. Subacute combined degeneration of the spinal cord
4. Dec Serum Vitamin B12
5. Inc serum homocysteine
6. Inc methylmalonic acid

Back 44

Vitamin B 12 deficiency macrocytic anemia

Front 45

Why does Vitamin B12 deficiency macrocytic anemia result in Subacute combined degeneration of the spinal cord?

Back 45

1. Vitamin B12 is a cofactor for the conversion of methylmalonic acid to succinyl CoA

2. W/o Vitamin B12 levels of methylmalonic acid inc which impairs spinal cord myelinization

3. Poor proprioception and vibratory sensation and spastic paresis

Front 46

What causes Normocytic anemia? How can you tell what's what?

Back 46

Anemia with normal-sized RBCs (80-100)

Due to inc peripheral destruction or underproduction (reticulocytes can help tell which one is which)

Front 47

How are young RBCs identified on blood smears?
What is the normal count?
Lifespan?
How does a properly functioning BM respond to anemia?

Back 47

larger cells with bluish cytoplasm (residual RNA)
- 1-2% reticulocyte count
- 120 days
- inc reticulocyte count to 3%

Front 48

How does the Reticulocyte appear to be falsely evelated? How is it corrected?

Back 48

- Reticulocyte are a measure as percentage of total RBCs, dec in total would falsely inc it

- Corrected by multiplying reticulocyte count by Hct/45
1. correct >3% good response and peripheral destruction
2. correct <3% poor response and underproduction

Front 49

Describe the findings for normocytic peripheral RBC destruction (hemolysis) => Extravascular so by marcophages in the spleen, liver, or lymph nodes.

Back 49

1. Macrophage consume RBCs and break down hemoglobin => globin broken into amino acids and heme into recycled iron
2. Protoporphyrin => unconjugated bilirubin

Clinical findings:
anemia with splenomegaly, jaundice, and inc risk for gall stones
marrow hyperplasia with corrected reticulocyte count >3%

Front 50

Describe Intravascular normocytic peripheral RBC is the destruction of RBCs where? Clinical findings? 3

Back 50

within the vessels
1. Hemoglobinemia
2, Hemoglobinuria
3. Hemosiderinuria => renal tubular cells pick up hemoglobin that is filted through the urine and break it down into iron and accumulates as hemosiderin

Front 51

What are the types of Normocytic anemias with predominant extravascular hemolysis?

Back 51

1. Hereditary spherocytosis -

2.Sickle cell anemia

3. Hemoglobin C

Front 52

What is Hereditary spherocytosis?

Back 52

1. defect in RBC cytoskeleton-membrane tethering proteins (spectrin or ankyrin) this causes the RBCs to become sphere shaped instead of disc shaped so they can't move through blood as well and get eaten by the spleen

Front 53

LABS:
1. Spherocytes with loss of central pallor
2. INC RDW and INc mean corpuscular volume
3. Splenomegal, jaundice with unconjugated bilirubin, and inc risk for gall stones
4. inc risk for aplastic crisis with parvovirus B19

Back 53

Hereditary spherocytosis

Front 54

How is Hereditary spherocytosis dx and tx?

Back 54

dx - osmotic fragility test => spherocytes fragility in hypotonic solution

tx - splenectomy: anemia resolves but spherocytes persist and Howell-Jolly bodies (fragments of nuclear material appear

Front 55

What is the autosomal recessive mutation in sickle cell anemia?

Back 55

Mutation in beta chain of hemoglobin where a single amino acid change replaces normal glutamic acid (hydrophilic) with valine (hydrophobic)

- the disease arises when two abnormal beta genes are present

Front 56

Treatment with what prolongs the protective effect of HbF against sickle cell anemia?

Back 56

Hydroxyurea

Front 57

What can sickle cell anemia be protective against?

Back 57

falciparum malaria

Front 58

What does the massive erythroid hyperplasia with sickle cell anemia result in? 3

Back 58

1. Expansion of the hematopoiesis => crewcut on xray and chipmunk facies

2. hepatomegaly

3. aplastic crisis with parvovirus B19

Front 59

Irresversible sickling leads to complications of vaso-occlusion such as... 5

Back 59

1. Dactylitis - swollen hands and feet due to infarcts in bones, like with infants

2. Autosplenectomy - shrunken, fibrotic

3. Acute Chest syndrome - chest pain, SOB, most common cause of death

4. Pain crisis

5. Renal Papillary necrosis

Front 60

What are some of the consequences with autosplenectomy in sickle cell anemia causing a shrunken and fibrotic spleen?

Back 60

1. inc infections with encapsulated organisms such as strep pneumonia and H. influenza => most common cause of death in kids

2. inc risk of Salmonella paratyphi osteomyelitis

3. Howell-Jolly bodies on blood smear

Front 61

What are some lab findings in sickle cell anemia? 4

Back 61

1. Sickle cells - disease

2. Target cells - disease

3. Metabisulfite screen causing cells with any amount of HbS - disease and trait

4. Hb electrophoresis confirms the presence and amount of HbS

Front 62

What occurs in Hemoglobin C?
Presentation?
Blood smear?

Back 62

- it's an autosomal recessive mutation of beta chain hemoglobin where normal glutamic acid is replaced by lysine

- mild anemia due to extravascular hemolysis

- HbC crystals are seen in RBCs on blood smear

Front 63

What are the different types of Normocytic anemias with predominant intravascular hemolysis?

Back 63

1. Paroxysmal nocturnal hemoglobinuria
2. Glucose-6-Phosphate dehydrogenase deficiency
3. Immune hemolytic anemia
4. Microangiopathic hemolytic anemia
5. Malaria

Front 64

What is Paroxysmal Nocturnal Hemoglobinuria?

Back 64

- Acquired defect in myeloid stem cells resulting in absent glycosylphosphatidylinositol which renders cells susceptible to destruction by complement

- the absence of GPI anchoring protein leads to Decay accelerating factor (DAF) that usually inhibits C3 convertase and protects the cell not being attached

Front 65

When do pt with Paroxysmal nocturnal hemoglobinuria have the most problems and why?

Back 65

mild acidosis develops during sleep with shallow breathing and activates complement => intravascular hemolysis =>

Front 66

What screens for Paroxysmal nocturnal hemoglobinuria?

What confirms?

Back 66

- sucrose test screens

- flow cytometry confirms by testing for lack of CD55 (DAF) on blood cells

Front 67

What is the main cause of death with Paroxysmal nocturnal hemoglobinuria?

Back 67

thrombosis (from the destroyed platelets )of the hepatic, portal, or cerebral veins

Front 68

What is glucose-6-Phosphate dehydrogenase deficiency?
Presentation?

Back 68

1. X linked resulting in reduced half life of G6PD leaving the cell open to oxidative stress

dec G6PD => dec NADPH => dec reduced glutathione causes oxidative injury => intravascular hemolysis

2. Hemoglobinuria and back pain with Heinz bodies being removed from RBCs = bite cells.

Front 69

Variants of G6PD?

Back 69

1. African - mild

2. Mediterranean - even less G6PD, worse

Front 70

What are the two types of immune hemolytic anemia that results in normocytic anemia?

Back 70

1. IgG = extravascular in warm temp of central body, destroyed by spleen
- associated with SLE, drugs, and CLL

2. IgM = binds in colder regions of the body, extremities assoc. with Mycoplasma pneumoniae and intravascular

Front 71

How are the different immune hemolytic anemias dx?

Back 71

Coombs

1. Direct - are they attached

2. Indirect - are they in the blood

Front 72

How does the intravascular normocytic microangiopathic hemolytic anemia develop?

Back 72

1. Microthrombi - TTP-HUS, DIC, HELLP
2. prosthetic heart valve
3. aortic stenosis

Front 73

How can parvovirus B19 result in anemia?

Back 73

infects RBC progenitor cells and temp halts erythropoisis

- tx is supportive

Front 74

What is damage to hematopoietic stem cells resulting in pancytopenia => anemia, thrombocytopenia, and leukopenia result with low reticulocyst count result in?

Back 74

Aplastic anemia with empty, fatty marrow