Heme Flashcards Preview

Question 1

1

Normoblasts

Answer

Nucleated RBCs

Question 2

2

Reticulocytes

Answer

When nucleated RBCs lose their nucleus (5-7 days)

Question 3

3

What causes left shift of O2 binding

Answer

Increase pH
Decrease DPG/Temp

Question 4

4

What causes right shift of O2

Answer

Decreased pH
Increased DPG/TEMP

Question 5

5

What is the major Hemoglobin structure for adults

Answer

HbA (alpha/beta) 95%

Question 6

6

Why are RBCs binconcave in shape

Answer

Enables max O2 saturation
Allows passage through small capillaries and splenic sinusoids

Question 7

7

Anemia

Answer

Lower than normal total circulating red cell mass

Question 8

8

Mean cell volume

Answer

MCV
Volume of RBC
Femtoliters

Question 9

9

Mean cell hemoglobin

Answer

MCH
Average content of Hb
Picograms

Question 10

10

Mean cell hemoglobin concentration

Answer

MCHC
Concentration of Hb in given packed RBCs

Question 11

11

Red cell distribution

Answer

RDW
Coefficient of variation of RBC volume

Question 12

12

Anemia due to acute hemorrhage, what is the immediate concern

Answer

Hypovolemia

Question 13

13

Are the majority of hemolytic anemias found intravascular or extravascular

Answer

Extravascular

Question 14

14

Intravascular hemolysis Causes

Answer

Complement fixation: BIGGEST! think of blood mismatching
Mechanical injury
Infections/ intracell parasites, toxins

Question 15

15

What happens to RBCs in extravascualr hemolysis

Answer

RBCs rendered less deformable
RBCs thought as foreign

Question 16

16

Lab: PB- normochromic, normocytic anemia, increased reticulocytes
BM- erythroid hyperplasia
Serum: Increased unconjugated bili, increase LDH, low haptoglobin

Answer

Hemolytic anemia

Question 17

17

Urine: hemosiderinuria, +/- hemoglobinuria

Answer

Intravascular hemolysis

Question 18

18

Hereditary intrinsic RBC defects

Answer

Spherocytosis: membrane defect
G6PD: Enzyme defect
Sickle: hemoglobin defect

Question 19

19

Acquired extrinsic RBC defects

Answer

Immune mediated damage
Nonimmune mediated damage
Sequestration- hypersplenism

Question 20

20

Who has highest incidence of spherocytosis

Answer

N. Europeans

Question 21

21

What is the genetic pattern for spherocytosis

AD

Answer

10-20 days

Answer

Ankyrin (75%)
Band (20%)
Ankyrin, spectrin, band 4.1, band 4.2

Answer

Deformed RBC (more spherical) unable to traverse splenic sinusoids, phago by splenic macrophages

Answer

Splenectomy

Answer

hereditary spherocytosis

Answer

Osmotic fragility test
In 65% of patients RBCs lyse prematurely when exposed to hypotonic salt solutions

Answer

Hexose monophosphate shunt (glutathione metabolism)

Answer

A: 10% africans
Mediteranian: mostly middle east

Answer

P. Falciparum malaria

Answer

Denatured hb in RBCs
G6PD

Answer

SH groups on globin chains hb

Answer

G6PD
Splenic macrophages bite out inclusions (extravascular)

Answer

Recessive X linked

Answer

RBC dz mutation in globin genes
Defective hemoglobins

Answer

Lesions in globin genes
Decreased synthesis of globin chains

Answer

Point mutation of position 6 in beta globin gene
Glutamic acid replaced by valine

Answer

Heterozygote sickle cell trait
AS

Answer

Falciparum malaria

Answer

Essentially all non "white" countries

Answer

Initially, but at chronic stage its not

Answer

HbA/HbF - decrease sickle
HbC- Increased sickle

Answer

HbC
Dehydration
Low pH
Low O2 tenison

Answer

HbA/HbF
co existing a-thalassemia

Answer

Hyperslenism kids
Autosplenectomy pts

Sickle pts

Answer

Repeated farction/fibrosis

Answer

Microvascular occlusions
Kids- kidneys
Adults- leg ulcers

Answer

Kids/young adults
Rapid pooling of blood in spleen
Sickle cell

Answer

Acute viral infection
Parvo B19 (infects red cell precursors)
Sickle cell

Answer

PB- sickled cells
Mix blood with metabisulfite (should induce sickling)(reduction test)
Hb electrophoresis
DNA screen

Answer

Hydroxyurea

Answer

Penicillin

Answer

50% survive to age 50

Answer

Acute chest syndrome
Stroke
Adult- organ failure

Answer

Thalassemia

Answer

Chrom 11
Point mutation of beta
B1/ B2

Answer

Chrom 16
Deletion of alpha globin chain
a1/a2/a3/a4

Answer

Old world distribution

Answer

Diminished synthesis of struct normal B globin chain
unpaired a chain production

Answer

Reduced B chains produced
Mutation in promotor region of gene

Answer

No B chains made (homozygote)
Mutation in splicing or chain termination

Answer

Ineffective erythropoiesis
B- thalassemia

Answer

Dietary iron

Answer

Extramedullary hematopoiesis

Answer

B+/B+, B+/ B0, B0/B0

Answer

Severe transfusion dependent anemia

Answer

B+/B or B0/B

Answer

Mild asymptomatic anemia

Answer

Milder versions of 1 thalassemia
Severe variants in 2
1 combined with a thalassemia

Answer

Meiterranean
Parts of Africa
SE asian

Answer

6-9 months since HbF starts to fall

Answer

Hb: 3-6 g/dl
HbF remains high
HbA2 normal, low or high

Answer

B thalassemia major

Answer

B thalassemia minor
Make sure not to tx with iron (iron overload will be exacerbated

Answer

Regular blood transfusions
Iron chelators to prevent overload
Bone marrow transplant

Answer

one a gene deleted

Answer

2 a genes deleted
a/a -/- (SE Asian)
a/- a/- (African)

Answer

SE asian variant
a/a -/-

Answer

a thalassemia... 3 genes deleted

Answer

a thalassemia... 4 genes deleted incompatible with life

Answer

excess B chains with a lack of a chains, has a high affinity for O2, produces severe tissue hypoxia.

HbH prone to oxidation-> inclusions in older RBCs-> extravascular hemolysis (spleen)- > moderate anemia

Answer

Excess of gama chains in utero-> extremely high O2 affinity, O2 doesnt reach tissues

Answer

Intrauterine transfusions

Answer

Mutations of X linked gene of phosphatidyloinositol glycan class A (PIGA)

Rare acquired clonal stem cell disorder- associated with periodic hemolysis

Answer

Defective PIGA-> Needed to synthesize GPI- cell membrane glycolipid anchor for attachment of certain proteins to cell surfaces

Selective advantage hypothetically gained via autoimmune destruction of GPI linked proteins Hemolysis occurs

Answer

CD55, CD59, C8 binding protein
Increases susceptibility to hemolysis

Answer

Paroxysmal nocturnal hemoglobinuria

Answer

Thrombosis (40% DVT)

Answer

Aplastic anemia

Answer

AML
Meylodysplastic syndrome

Answer

immunosuppression/ bone marrow transplantation

Answer

Iron deficiency

Answer

Cooombs test
Direct antiglobulin test (DAT)
Indirect Antiglobulin Test ( IDAT)

Answer

DAT
Detection of antibodies+/- complement on patient RBCs

INcubate w/ cold: IgM
Incubate w/ warm: IgA IgG

Answer

IDAT
Test serum for ability to agglutinate test RBCs that have known antibodies bound to them

Answer

50% idiopathic
50% predisposing diseases( autoimmune disease, lymphoma, drug reactions)

Answer

Infections
Mycoplasma pneumonia
Infectious mono
CMV
Influenza
HIV

Answer

Idiopathic
Associated with low grade lymphoma

Answer

Cardiac valve prosthesis
Microvascular obstruction
DIC
Malignant HTN
SLE
Cancer

Answer

Stem cell defect

Answer

Defective Vitamin B12 or Folate

Answer

DNA synthesis

Answer

Megaloblastic anemia

Answer

Megaloblastic anemia

Answer

Methylmalonyl coA -> succinyl coA

Answer

B12 deficiency megalblastic anemia

Answer

Megaloblastic anemia
Vit B 12

Answer

Animal products

Answer

Pepsin and pancreatic proteases release B12 from food-> B12 binds to IF from parietal cells-> active absorption in ileium

Answer

Decreased intake (strict veg)
Impaired absorption (prenicious anemia)
Increased requirement (prego/growing child)

Answer

Immune destruction of gastric mucosa
Failure of IF production
B12 not absorbed

Answer

N. Europeans 40-80 yrs

Answer

Can determine b12 def or prenicious anemia

Answer

serum antibodies to IF

Answer

Green vegs/ fruits.... SHould be raw... cooking destroys folate

Answer

Decreased intake (inadequat diet/ alcholics)
Impaired absorption
Increased requirements (prego/ infancy)

Answer

Megalobalstic Folate def

Answer

Dietary def (dev countries)
Imapaired absorption
Increased requirements
Chronic blood loss

Answer

GI bleeds
Menstraul bleeds

Answer

Animal products

Answer

hepcidin
made in the liver

Answer

Storage of iron

Answer

Partly degraded aggregates of ferrritin

Answer

Iron transport

Answer

100-120 micrograms

Answer

Iron deficiency anemia

Answer

No iron stored in BM

Answer

Anemia of chronic disease

Answer

Chronic bacteria/ immune/ malignant tumors

Answer

Anemia of chronic disorders

Answer

Anemia of chronic dz

Answer

ACD: Transferrin reduced or low, Ferritin normal/inc
IDA: Transferrin increased, ferritin reduced

Answer

Aplastic anemia

Answer

Congenital/ hereditary (fanconi anemia)
Acquired

Answer

65% of cases
Possibly immune related destruction of stem cells (t cells)- Suspected in most cases
Possibly intrinsic stem cell defect

Answer

35% of cases
Chemical agents: (chemo/ idiosyncratic )
Physical agents: whole body radiation
Viral agents: Hepatitis (not ABCG), CMV/ EBV/Herpes zoster

Answer

Aplastic anemia

Answer

Bone marrow biopsy

Answer

Children since it is probably viral etiology

Answer

Allogeneic bone marrow transplant in younger patients
Immuno suppression in older adults

Answer

Aplastic anemia
Myelophthisic anemia
Diffuse liver disease
Chronic renal failure

Answer

BM replaced by abnormal infiltrates (replaced w/ fibrosis)
Metastatic ca, granulomatous inflammation
PB- leukoerythroblastic

Answer

BM hypofunction, affects mainly RBCs

Answer

Multifactorial anemia
Drop in erythropoietin (produced in kidney)

Answer

Abnormally elevated RBC concentration

Answer

Due to reduced plasma volume
Secondary to dehydration

Answer

Primary/ secondary

Answer

Polycythemia vera
Chronic myeloproliferative neoplasm

Answer

Appropriate EPO levels: lung dz, cyanotic heart dz, living in mountains

Innappropriate EPO- EPO secreting tumors (kidney/liver cancers)

Answer

Platelet defect

Answer

Extrinsic and common coagulation pathways

Answer

Test of intrinsic and common pathways

Answer

Fibrinogen

Answer

Reduced number of platelets, prolonged bleeding times

Answer

Normal platelet count, prolonged bleeding times

Answer

Drugs- Nsaids
Uremia- chronic renal failure

Answer

Decreased platelet production
Decreased platelet survival
Sequestration in spleen
Dilutional

Answer

BM dz
Aplastic anemia
Marrow infiltration
Drug induced
Infections
Megaloblastic anemia
Myelodysplastic syndromes

Answer

Immune destruction
Non immune destruction

Answer

Antiplatelet antibodies
Autoimmune: Primary ITP (immune thrombocytopenia), Secondary ITP (SLE/lymphoma)
Isoimmune: Post transfusion (seen in neonates)
Drug associated: Heparin/ antiB
Infection associated: HIB/CMV/ Mono

Answer

DIC
TTP/HUS
Giant hemangiomas
Microangiopathic hemolytic anemias

Answer

Uncommon
Children
Post viral
Spontaneous resolution

Answer

Common
Women 20-40
Skin/mucosal bleeding
Does not resolve spontaneously

Answer

immunosupression (steroids)
Splenectomy

Answer

Chronic immune thrombocytopenia

Answer

Syndrome of fever
Thrombocytopenia
Microangiopathic hemolytic anemia
Transient neuro deficits
Renal failure

Answer

No neruologic defecits (vs TTP)

Answer

Formation of platelet thrombi in small bv
Platelet consumption- thrombocytopenia
Platelet thrombi- small vessel occlusion
nonimmune thrombotic

Answer

Factor VIII
Von Willi
Factor IX

Answer

Typically multiple factor abnormalities
Vit K def
Liver dz
DIC

Answer

Factor VIII Hemophil A
Von Willibrand factor

Answer

Cofactor for Factor IX to activate Factor X

Intrinsic pathway

Answer

Promotes adhesion of platelet to the subendothelial layer after damage
Prolongs the half life of Factor VIII

Answer

Type 1/3: reduce quantity of VWF
Type 2 qualitative functional abnormality of VWF

Answer

70% of all cases of vwd
mild mucosal bleeding

Answer

25% of all cases of vwd
Mild to moderate bleeding

Answer

Severe deficiency/lack of VWF
affects F VIII stability

Answer

Type 3 VW dz

Answer

X linked recessive

Answer

Hemophilia A/ Factor VIII deficiency

Answer

Recombinant FVIII infusions

Answer

Systemic activation of coagulation sequence
Formation of microthrombi
Consumption of platelets/ clotting factors, secondary activation of fibrinolysis

Answer

Obstetric
Infections
Neoplasms
Massive tissue injury

Answer

Too few cells

Answer

Too many cells

Answer

Advanced HIV
Chemo/steroids
Autoimmune dz
Acute viral infections

Answer

Reduced production by BM
Accelerated consumption/destruction (peripheral problem)

Answer

Suppression of myeloid stem cells (aplastic anemia)
Suppression of committed myeloid precursors (drug related)
Ineffective granulopoieisis(mega anemia)
Marrow infiltration
Kostmann syndrome

Answer

Immune related (idiopathic dz, drugs)
Splenic sequestration (splenomegaly)
Increased consumption (infection)

Answer

Severe neutropenia
Prone to infections
<500

Answer

Drug induced
Chemo

Answer

BM morphology
Infections secondary to agranulocytosis (candida/ aspergillus)

Answer

Neutropenia

Answer

Infections
Acute inflammation
Acute hemorrhage
Malignancy

Answer

Allergic disorders
SKin dz
Parasites
Drugs
Collagen vascular dz
Drug rx

Answer

Indicates myeloproliferative neoplasm

Answer

Chronic infections
Collagen vascular dz (SLE)
Inflammatory bowel dz

Answer

Chronic immunological stimulation
Mono
VIral infections (EBV/HEP A/ CMV)
B. Pertussis

Answer

Sky blue cytoplasm found on neutrophils

Answer

Viral infections

Answer

Acute lymphadenitis

Answer

Follicular hyperplasia-b cell response
Paracortical hyperplasia- T cell response
Sinus histiocytosis- dilated sinusoids, containing phagocytic histiocytes
Medulla- plasmacytosis

Answer

Chromosomal translocations/oncogenes
Inherited genetic factors
Viruses
Environ agents
Iatrogenic

Answer

EBV, HTLV1, KSHV/HHV-8

Answer

Neoplasia with predominant BM involvement /PB as well

Answer

Neoplasia w. masses in lymph nodes/extranodal at time of presentation

Answer

Has Precursor cells predominates

Answer

Differentiated mature cells predominate

Answer

Extranodal
Will have site related sx

Answer

Plasma cell neoplasms

Answer

Histological examination
PCR/Southern blot to detect antigen receptor gene rearrangment

Answer

Flow cytometry or immunohistochemical stains
Detect light chains Kappa/ lambda chains!

Answer

B cell lymphomas 90%

T cell 10%

Answer

Diffuse large B cell lymphomas
Follicular
Small
MALT
MCL

Answer

Follicular lymphoma

Answer

Germinal center B cells

Answer

Diffuse pattern
Increased number of large cells

Answer

CD19/20/10+

Answer

Indolent/ incurable

40% transform to aggressive DLBL survival <1 year

Answer

Median 60
Wide age range

Answer

Diffuse large B cell Lymphoma

Answer

Diffuse large B cell lymphoma

Answer

Aggressive
Potentially curable
CXT (chemotherapy)

Answer

Chronic lymphocytic leukemia

Answer

Small lymphocytic lymphoma/ Chronic lymphocytic leukemia (SLL/CLL)

Answer

CD19, 20, 5, 23, 43

Answer

Incurable
Overall survival 4-6 years

Answer

Progressive pancytopenia -> Infections/ bleeding
Transformation into more aggressive neoplasm -> Prolymphocytic leukemia (20%), Diffuse large B cell (10%)

Answer

Marginal zone lymphoma (maltoma)

Answer

Stomach- usually superimposed on helicobacter gastritis

Answer

Antibiotics to remove the helicobacter gastritis that is usually found with MALT

Answer

autoimmune inflammation

Answer

African (endemic)

Answer

Sporadic (non-endemic)

Answer

HIV associated Burkitt

Answer

CD 19/20/10

Answer

(8;14), (2;8), (8;22)

Answer

Chrome 8= c-myc oncogene

Answer

kids/ young adults

Answer

Endemic: mandible, kidneys, ovaries, adrenal glands
Sporadic: Abdominal

Answer

Older adults

Answer

CTX high dose

Answer

middle aged males
4:1 M:F

Answer

Hairy cell leukemia

Answer

CD 20, 11c, 25, 103+

Answer

light chains

Answer

Mid age or older (50-60)
M>F

Answer

Multiple myeloma

Answer

hypercalcemia
Bence jones proteins
Amyloid deposition

Answer

multiple myeloma

Answer

end organ damage

Answer

Alkylating agent ctx
Younger pts can have allogeneinc bone marrow transplant

Answer

HD: tumor cell minority, Orderly spread, very little extranodal involvement, Involvement of single axial node group

NHL: Tumor cells majority, Spread is not predictable, Extranodal presentation normal, multiple peripheral nodes involved

Answer

I single node region
II 2 or more LN on same side of diaphragm
III LN on both sides diaphragm
IV multiple/disseminated involvement of 1 or more extralymphatic organs/ tissues

Answer

CD 15+, 30+, 45-

Answer

CD 20+, 45+, 15- 30-

Answer

Nodular sclerosis 65%
Mixed cellularity 25%
Lymphocyte rich
Lymphocyte depleted

Answer

Lymphocyte predominant 5%

Answer

Classical HD

Answer

Classical HD

Answer

Young adults, then again >55 M>F

Answer

Diffuse nodal replacement
RS cells
EBV+

Answer

Abundant RS cells
EBV +
few lymphocytes/ fibrosis

Answer

Elderly, HIV+, usually present at advanced stage IV

Answer

Varient HD (lymphocyte depleted)

Answer

Certival ax nodes
Can recur
<5% transform to NHL large B cells lymphoma

Answer

Long term survivors get secondary cancers (AML, lung ca)

Answer

b-cell types
Childhood acute leukemias

Answer

precursor T cell neoplasms
Medistinal mass
Usually seen in adolescent males

Answer

Morphology: AML- granules/ auer rods
Histo stain: ALL- MPO, Sudan black. AML- PAS
ALL abnormal cytogenetics

Answer

Thymic enlargement

Answer

Testicular enlargment, CNS involvement (headaches, blurred vision, vomiting)

Answer

2-10 yrs
WBC count low
Immunophyenotype: pre b cell
Cytogentics: hyperdiploidy t(12;21)

Answer

100,000
t(9;22)

Answer

BM, peripheral blood, secondary hematopoietic organs (liver, spleen, nodes)

Answer

adults, peaks after 60

Answer

1. AML w/ recurrent chrom rearrangements
2. AML w/ multilineage dysplasia
3. AML, therapy related
4. AML, not specified

Answer

recurrent chromosomal rearrangements

Answer

maturation of granulocyte

Answer

Blast cells

Answer

15;17, 8;21, 16;16
Seen in younger adults with AML

Answer

Translocations involving chromosome 11

Answer

Older adults with AML
or post chemo

Answer

Translocations disrupts differentiation
Chimeric genes-> block terminal differentiation
Mutated tyrosine kinase-> increased cell proliferation
Accumulation of proliferating neoplastic precusors in BM- suppresses normal hematopoitic progenitors

Answer

1.BM aspirate/ biopsy
FLow cytometry
Cytogenetics

Answer

Chimeric protein- RARa-PML blocks differentiation beyond promyelocytes

Tx with vitamin A deriverative (all trans retinoic acid)

Answer

8;21
inv 16

Answer

Del 5 or 7

Answer

Clonal maturation defects in stem cells causing abnormal differentiation

Answer

>50, gradual onset

Answer

transforms to AML
Survival 9-30 months

Answer

MDS

Severe MDS increased blast cells

Answer

allo-BMT in young
supportive rx in older pt

Answer

Arise from multipotent progenitor cells
Mutated- constitutively activated TK- circumvent normal growth controls

Answer

t(9;22) Phila
BCR-ABL fusion

Result- constitutively ABL kinase activation

Answer

JAK2 point mutation

Result- constitutive JAK2 kinase activation

Answer

JAK2 point mutation
MPL point mutation

Constitutive kinase activation

Answer

BM filled with neoplastic cells. supress normal hematopoiesis
Transforms to CML

Answer

Defect in pluripotent stem cell for myeloid and lymphoid lineages

Mainly granulocytic, uncontrolled proliferation

Answer

9;22
Philadelphia, BCR-ABL

Answer

Imatinib- inhibits BCR-ABL kinase
Allogenic bone marrow transplant good for younger pts

Answer

autoimmune haemolytic anaemia

Answer

Elevated unconjugated bilirubin
GALL STONES
– SPLENOMEGALY
– Howell Jolly bodies (purple blue nuclear remnants) may be present after splenectomy i.e. removal of spleen

Answer

CD 55 (decay accelerating factor)
– CD59(membraneinhibitorofreactivelysis-potentinhibitorofC3 convertase

Answer

Susceptible to complement especially in acidic states (sleep)

Answer

Autoimmune haemolytic anaemias are Coomb’s
test positive
• Direct Coomb’s test
– anti – Ig antibody (antihuman antiglobulin) is
added to patient’s RBCs
– Agglutinate if RBCs are coated with anti-RBC
surface Ig
• Indirect Coomb’s test
– Normal RBCs and anti-Ig antibody are added to
patients serum

Answer

Sickle cell

Answer

Sickle
B-Thalasemia major

Answer

Single dot of nuclear remnant
Postsplenectomy
– Haemolyticanaemia
– Megalobasticanaemia

Answer

Leadpoisoning
– Thalassaemia(esp. βthalassaemia major)
– Megaloblasticanaemia

Answer

Ineffective erythropoiesis

Answer

since synthesis of Hb requires Iron to be inserted into protoporphyrin IX

Iron Def anemia

Answer

Sideroblastic anemia

Answer

Idiopathic
– Inherited (Fanconi’s anaemia)
– Acquired – drugs (most common cause of all), viruses (e.g. Hepatitis C) chemicals, toxins,
irradiation

Answer

EBV
CMV
Toxoplasm

Answer

Proliferation of B cells
Antibodies against IgG IgM

Answer

Ballerina cells MONO

Answer

Hairy cell leukemia

Answer

Hairy cell leukemia

Answer

Lytic lesions
Multiple Myeloma

Answer

hyperviscostiy syndrome

Answer

Multiple myeloma

Answer

megakaryocytes- > Release of growthfactors (TGFβ and PDGF) by megakaryocytes -> extensive fibrosis and angiogenesis

Answer

12, 11, 9, 8

Question 22

22

What is the lifespan of RBCs in spherocytosis

Question 23

23

What are the proteins affected in spherocytosis

Question 24

24

Why is there splenomegaly in spherocytosis

Question 25

25

Tx of spherocytosis

Question 26

26

mild to chronic hemolytic anemia
Induced aplastic/ hemolytic crisis

Question 27

27

What is the one test for spherocytosis

Question 28

28

G6PD is in which cycle

Question 29

29

What are the G6PD variants which cause disease

Question 30

30

G6PD is protective against

Question 31

31

What is the most common G6PD varient in people

G6PD B

Question 32

32

Heinz bodies

Question 33

33

Oxidation where causes hb to denature/ precipitate

Question 34

34

Bite cells

Question 35

35

Genetic of G6PD

Question 36

36

Acute hemolysis after oxidant stress, infection, fava beans

G6PD

Question 37

37

Hemoglobinopathies

Question 38

38

Thalassemia syndromes

Question 39

39

Genetic issue in sickle cell

Question 40

40

40% HbS

Question 41

41

Sickle is protective against

Question 42

42

Malaria endemic where

Question 43

43

Is sickling in Sickle cell reversible

Question 44

44

Which hb's predispose to sickling

Question 45

45

What predisposes you to increased sickling in sickle cell

Question 46

46

What predisposed you to decreased sickling

Question 47

47

Pt presidposed to encapsulated bacteria
H influ
Pneumococcus

Question 48

48

Why hypersplenism in kids during sickle cell

Question 49

49

Where does sickle crisis take palce (vaso-occlusive)

Question 50

50

Sequestration cirsis

Question 51

51

Aplastic crisis

Question 52

52

Diagnosis of sickle

Question 53

53

What is one way to increase HbF to tx sickle cell

Question 54

54

Give prophilactic what for sickle cell

Question 55

55

Outcome of HbSS

Question 56

56

What is the major cause of death in sickle for child <5

infection

Question 57

57

What is most likely going to kill someone with sickle

Question 58

58

Is thalasemia intrinsic or extrinsic hemolytic anemia

Intrinsic

Question 59

59

Lab- Hypochromic, microcytic, low levels of normal Hb
Insoluble inclusions

Question 60

60

Beta globin gene is found where

Question 61

61

Alpha globin gene found where

Question 62

62

Distribution of thalassemia

Question 63

63

B thalassemia

Question 64

64

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Normoblasts

Nucleated RBCs

Reticulocytes

When nucleated RBCs lose their nucleus (5-7 days)

What causes left shift of O2 binding

Increase pHDecrease DPG/Temp

What causes right shift of O2

Decreased pHIncreased DPG/TEMP

What is the major Hemoglobin structure for adults

HbA (alpha/beta) 95%

Why are RBCs binconcave in shape

Enables max O2 saturationAllows passage through small capillaries and splenic sinusoids

Anemia

Lower than normal total circulating red cell mass

Mean cell volume

MCVVolume of RBC Femtoliters

Mean cell hemoglobin

MCHAverage content of Hb Picograms

Mean cell hemoglobin concentration

MCHC Concentration of Hb in given packed RBCs

Red cell distribution

RDW Coefficient of variation of RBC volume

Anemia due to acute hemorrhage, what is the immediate concern

Hypovolemia

Are the majority of hemolytic anemias found intravascular or extravascular

Extravascular

Intravascular hemolysis Causes

Complement fixation: BIGGEST! think of blood mismatching Mechanical injury Infections/ intracell parasites, toxins

What happens to RBCs in extravascualr hemolysis

RBCs rendered less deformable RBCs thought as foreign

Lab: PB- normochromic, normocytic anemia, increased reticulocytes BM- erythroid hyperplasia Serum: Increased unconjugated bili, increase LDH, low haptoglobin

Hemolytic anemia

Urine: hemosiderinuria, +/- hemoglobinuria

Intravascular hemolysis

Hereditary intrinsic RBC defects

Spherocytosis: membrane defect G6PD: Enzyme defect Sickle: hemoglobin defect

Acquired extrinsic RBC defects

Immune mediated damage Nonimmune mediated damage Sequestration- hypersplenism

Who has highest incidence of spherocytosis

N. Europeans

What is the genetic pattern for spherocytosis

AD

What is the lifespan of RBCs in spherocytosis

10-20 days

What are the proteins affected in spherocytosis

Ankyrin (75%)Band (20%)Ankyrin, spectrin, band 4.1, band 4.2

Why is there splenomegaly in spherocytosis

Deformed RBC (more spherical) unable to traverse splenic sinusoids, phago by splenic macrophages

Tx of spherocytosis

Splenectomy

mild to chronic hemolytic anemia Induced aplastic/ hemolytic crisis

hereditary spherocytosis

What is the one test for spherocytosis

Osmotic fragility test In 65% of patients RBCs lyse prematurely when exposed to hypotonic salt solutions

G6PD is in which cycle

Hexose monophosphate shunt (glutathione metabolism)

What are the G6PD variants which cause disease

A: 10% africans Mediteranian: mostly middle east

G6PD is protective against

P. Falciparum malaria

What is the most common G6PD varient in people

G6PD B

Heinz bodies

Denatured hb in RBCs G6PD

Oxidation where causes hb to denature/ precipitate

SH groups on globin chains hb

Bite cells

G6PD Splenic macrophages bite out inclusions (extravascular)

Genetic of G6PD

Recessive X linked

Acute hemolysis after oxidant stress, infection, fava beans

G6PD

Hemoglobinopathies

RBC dz mutation in globin genes Defective hemoglobins

Thalassemia syndromes

Lesions in globin genes Decreased synthesis of globin chains

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Increase pH
Decrease DPG/Temp

Decreased pH
Increased DPG/TEMP

Enables max O2 saturation
Allows passage through small capillaries and splenic sinusoids

MCV
Volume of RBC
Femtoliters

MCH
Average content of Hb
Picograms

MCHC
Concentration of Hb in given packed RBCs

RDW
Coefficient of variation of RBC volume

Complement fixation: BIGGEST! think of blood mismatching
Mechanical injury
Infections/ intracell parasites, toxins

RBCs rendered less deformable
RBCs thought as foreign

Lab: PB- normochromic, normocytic anemia, increased reticulocytes
BM- erythroid hyperplasia
Serum: Increased unconjugated bili, increase LDH, low haptoglobin

Spherocytosis: membrane defect
G6PD: Enzyme defect
Sickle: hemoglobin defect

Immune mediated damage
Nonimmune mediated damage
Sequestration- hypersplenism

Ankyrin (75%)
Band (20%)
Ankyrin, spectrin, band 4.1, band 4.2

mild to chronic hemolytic anemia
Induced aplastic/ hemolytic crisis

Osmotic fragility test
In 65% of patients RBCs lyse prematurely when exposed to hypotonic salt solutions

A: 10% africans
Mediteranian: mostly middle east

Denatured hb in RBCs
G6PD

G6PD
Splenic macrophages bite out inclusions (extravascular)

RBC dz mutation in globin genes
Defective hemoglobins

Lesions in globin genes
Decreased synthesis of globin chains

Point mutation of position 6 in beta globin gene
Glutamic acid replaced by valine

Heterozygote sickle cell trait
AS

HbA/HbF - decrease sickle
HbC- Increased sickle

HbC
Dehydration
Low pH
Low O2 tenison

HbA/HbF
co existing a-thalassemia

Pt presidposed to encapsulated bacteria
H influ
Pneumococcus

Hyperslenism kids
Autosplenectomy pts

Sickle pts

Microvascular occlusions
Kids- kidneys
Adults- leg ulcers

Kids/young adults
Rapid pooling of blood in spleen
Sickle cell

Acute viral infection
Parvo B19 (infects red cell precursors)
Sickle cell

PB- sickled cells
Mix blood with metabisulfite (should induce sickling)(reduction test)
Hb electrophoresis
DNA screen

Acute chest syndrome
Stroke
Adult- organ failure

Lab- Hypochromic, microcytic, low levels of normal Hb
Insoluble inclusions

Chrom 11
Point mutation of beta
B1/ B2

Chrom 16
Deletion of alpha globin chain
a1/a2/a3/a4

Diminished synthesis of struct normal B globin chain
unpaired a chain production

Reduced B chains produced
Mutation in promotor region of gene

No B chains made (homozygote)
Mutation in splicing or chain termination

Ineffective erythropoiesis
B- thalassemia

Milder versions of 1 thalassemia
Severe variants in 2
1 combined with a thalassemia