Unit 3 - Formative 7 D4

Front 1

Pernicious Anemia

Back 1

Lack of intrinsic factor leads to inadequate B12 absorption which causes DNA synthesis impairment resulting in megaloblastic anemia (ineffective hematopoesis)

Front 2

What cells normally produce intrinsic factor?

Back 2

Gastric Parietal Cells

Front 3

What are the three autoantibodies found in pernicious anemia?

Back 3

1. Autoantibodies to gastric parietal cells (for screening, not specific)
2. Autoantibodies to IF (diagnostic)
3. Autoantibodies against IF-B12 complex receptor

Front 4

In what type of patient will all three pernicious anemia autoantibodies be found in?

Back 4

Chronic Gastritis

Front 5

What cells primarily mediate pernicious anemia?

Back 5

CD4+ T cells = Type IV Hypersensitivity

Front 6

What do RBC look like in megaloblastic anemia

Back 6

large erythrocytes; easily removed by phagocytes; ineffective hematopoiesis

Front 7

Pathogenesis behind megaloblastic anemia

Back 7

Vit B12/folate required for thymidine synthesis, DNA synthesis delated, delayed nuclear maturation compared to cytoplasmic maturation

Front 8

Extravascular hemolysis

Back 8

Antibodies to RBC; opsonized for phagocytosis by macrophages

Front 9

Intravascular hemolysis

Back 9

Antibodies to RBC; complement binds by classical complement pathway; RBC lysed internally by MAC

Front 10

Paroxysmal Noctural Hemoglobinuria

Back 10

ACQUIRED deficiency; GPI linked proteins not synthesized; RBC sensitivity to alternative complement pathway activation

Front 11

Ham's Test

Back 11

Acidification (acid hyperactivates alternative complement pathway) causes visible lysis of RBCs from PNH patients; theses pts also lyse more at night bc sleep decreases blood pH

Front 12

Function of DAF (CD55)

Back 12

Protects RBC from hemolysis

Inhibits formation of C3 convertase; this inactivates (alternative) complement pathway

In pts with normal DAF (GIP linked protein) RBC are not lysed

Front 13

Function of CD59

Back 13

Protects RBC from hemolysis

Inhibits addition of C9 thus inhibiting MAC formation

Front 14

Immunohemolytic Anemia

Back 14

Autoantibodies to RBC

Front 15

Warm Antibody Type Immunohemolytic Anemia

Back 15

IgG anti-RBC act as opsonins; RBC lose membrane, become spherocytes and are removed by the spleen (splenomegaly)

>30 yo

Front 16

Cold Aggulutination Type Immunohemolytic Anemia

Back 16

IgM antibodies agglutinate RBC at low temp

> 60 yo

Front 17

Two mechanisms for drug induced hemolytic anemia

Back 17

1. Drug acts as antigen; binds to RBC = hemolysis

2. Drug causes a break in tolerance (autoantibody against own Rh antigens, production ceases once drug is discontinued)

Front 18

Role of Coomb's Test

Back 18

Diagnosis of immunohemolytic anemia; demonstrates presence of antibodies or complemnt on patient's RBCs

Front 19

Direct Coomb's Test

Back 19

RBCs from patient mixed w/ antihuman antibodies; agglutination = positive result

Front 20

Indirect Coomb's Test

Back 20

Serum from patient is mixed with normal RBCs and antihuman antibodies; agglutination = positive

Front 21

Describe the role of CR1 on erythrocytes

Back 21

Ag-Ab complexes form in circulation w/ C3b; C3b binds to CR1 on erythrocytes; in spleen/liver phagocytic cells remove the immune complexes

Front 22

Solubility of 02 relative to C02

Back 22

C02 is 24x more soluble than 02

Front 23

Dalton's Law

Back 23

Percent concentration of each gas in a system must add up to 100%

Front 24

In alveolar air, oxygen is displaced from 21% (atmospheric conc) to 14%. Why?

Back 24

Oxygen is displaced by water vapor (which increases from .5% to 6.2%)

Front 25

Relationship between temperature and water vapor pressure

Back 25

Increased temperature = increased vapor pressure

Front 26

Equation to calculate partial pressure in body fluids

Back 26

(Atmospheric Pressure mmHg)(% Gas) = Partial Pressure mmHg

Front 27

What does the rate of oxygen loading into blood in alveolar tissue tell us?

Back 27

Since Blood P02 reaches almost 100% only 1/3 of the way down the pulmonary capillary, we could increase the blood flow (heart rate) significantly and still get 100% saturation

Front 28

where does oxygen bind on the hemoglobin molecule?

Back 28

Loosely binds to iron moiety; (remember carbon monoxide bonds 250x tighter than 02 to this site)

Front 29

What is the blood's capacity to carry dissolved oxygen?

Back 29

Very low

Front 30

What is the P02 level in oxygenated blood leaving the lungs relative to reduced blood returning from tissues

Back 30

Oxygenated P02: 80-120

Reduced P02: 20-40

Front 31

Compare the P02 in venous blood during exercise relative to normal

Back 31

P02 in blood during exercise is much lower (0-18) relative to normal venous blood (20-40)

Front 32

Relationship of P02 (mmHg) to percent 02 saturation of hemoglobin

Back 32

Positive logarithmic relationship; increased P02 increases percent 02 saturation of hemoglobin

Front 33

What is the P02 and Hb saturation of venous blood returning to lungs

Back 33

40 mmHg and a saturation of approximately 75%

Front 34

What is the P02 and Hb saturation of oxygenated blood leaving the lungs

Back 34

P02 = 100%
Saturation = 100%

Front 35

Relationship of PC02 to the hemoglobin dissociation curve

Back 35

Increasing PC02 shifts the curve to the right, meaning for an increase in PC02 there will be a decreased 02 saturation of hemoglobin and the blood will carry less oxygen

Front 36

Bohr Effect

Back 36

Lower pH causes a right shift in oxygen-hemoglobin saturation curve

Front 37

Is pH lower in the tissue or lungs? Why?

Back 37

Tissue; allows oxygen to be removed from blood as C02 is picked up by hemoglobin

In lungs pH increases which allows more 02 to bind to Hb

Front 38

Effects of temperature on Oxygen - Hb dissociation curve

Back 38

Increasing temp shifts curve to right, decreasing temp shifts curve to left

Front 39

Effects of 2,3-BPG on oxygen - hb dissociation curve

Back 39

Increasing 2,3 BPG shifts curve to right, decreasing 2,3 BPG shifts curve to left

Front 40

Difference between fetal hemoglobin and maternal hemoglobin 02 -Hb curve

Back 40

Fetal hemoglobin is shifted to the right and is more saturated at lower P02s then maternal hemoglobin

Front 41

Why is systemic arterial blood slightly below 100% P02

Back 41

Freshly oxygenated blood is mixed with pulmonary shunt blood that has not been oxygenated

Front 42

Relationship between blood flow and interstitial fluid P02 assumping normal 02 consumption

Back 42

Increased blood flow increases interstitial fluid P02

Front 43

Relationship between oxygen consumption and intestitial fluid P02

Back 43

Increasing oxygen consumption decreases intestitial fluid P02

Front 44

Relationship between C0 and Hb stauration

Back 44

Very low PC0 will produce 100% Hb saturation

Front 45

Relationship between blood flow and intestitial fluid PC02 in normal metabolism

Back 45

Decreasing blood flow increases interstitial fluid PC02, increasing blood flow decreases interstitial fluid PC02 (but minimally)

Front 46

How is C02 transported in the body

Back 46

1. C02 in plasma = 7%
2. Hg-C02 = 23%
3. HC03- = 70%

Front 47

What ion replaces bicarboante to maintain electrostatic imbalance/electroneutrality of cell

Back 47

Cl- (chloride shift)
Some water can also move into the cell, which indicates that in th venous blood rich in C02 the RBC may be slightly swollen due to increased movement of H20 into cell along w/ chloride - thus a slightly greater hematocrit taken from venous side relative to arterial side

Front 48

Haldane effect

Back 48

Deoxygenation of the blood increases its ability to carry C02; conversely oxygenated blood has a decreased capacity for C02 (which allows C02 to be dumped into the alveoli for excretion)

Front 49

How is iron excreted

Back 49

Menstruation, skin shedding, GI mucosa shedding

Front 50

Transferrin (TF)

Back 50

Binds to iron for transport

Front 51

Where is msot iron found?

Back 51

Bone marrow, mature erythrocytes (hemoglobin)

Front 52

Where does iron absorption take place?

Back 52

Duodenum (Heme = dietary, nonheme iron = cereals)

Front 53

Ascorbic Acid (Vitamin C)

Back 53

Reduces ferric acid to the more soluble and absorbable ferrous form

Front 54

Ferric Reductase

Back 54

Reduces ferric iron to the absorbable form ferrous

Front 55

Ceruoplasmin & hephaestin

Back 55

Ferrous converted to ferric state by ceruoplasmin in blood stream

Front 56

Ferritin

Back 56

Iron storage protein; binds ferric iron

Front 57

Hemosiderin

Back 57

Denatured aggregate of ferritin; poor source of iron in low iron conditions

Front 58

Elevated serum ferritin diseases

Back 58

Hemochromatosis

Front 59

Why does the body convert dietary ferrous iron to ferric iron and then back to ferrous iron for incorporation into heme?

Back 59

If they body didn't convert iron to ferrric form for transport, it would produce superoxides and damage blood cells/vascular endothelium

Front 60

Ceruoplasmin

Back 60

Converts iron from ferous to ferric state

Front 61

Low ceruoplasmin levels

Back 61

Wilson's disease; also associated with increased iron levels due to defective iron metabolism (ferrous -> ferric)

Front 62

Aceruoplasminemia

Back 62

Normal body copper metabolism but dramatic iron overload

Ceruoplasmins role is critical for iron metabolism and copper transport is secondary

Front 63

What determines how the cell responses to fluctuating intracellular iron concentrations?

Back 63

Location of Iron Rsponse Elements and Iron mediated affinity of binding protein to these elements

Front 64

Low soluble intracellular iron concentration; so cell wants iron uptake from plasma and restrict irion storage in ferritin; what does it do molecularly/

Back 64

Translation of transferrin receptor mRNA is stimulated
Translation of ferritin mRNA is inhibited to reduce storage

Front 65

Heme

Back 65

Fe + Protoporphyrin IX

Front 66

How does the final product of heme synthesis regulate itself?

Back 66

Heme inhibits the first commited step of heme synthesis (ALA synthase)

Front 67

ALA Synthase deficiency

Back 67

X linked Sideroblastic anemia

Front 68

Lead Poisoning

Back 68

Lead inhibits heme biosynthesis at the ferrochelatase step and porphobilinogen synthase step; hence synthesis of mature heme are deficient (symptoms = siderblastic anemia and porphyria)

Front 69

Precipitation Reaction

Back 69

Equimolar ratios of SOLUBLE antigen and antibody are mixed together, they form an insoluble latticework that precipitates naturally

Front 70

Prozone

Back 70

Antibody or antigen is in vast excess during a precipitation reaction and there is no precipitate

Front 71

Zone of Equivalence

Back 71

Max precipitate formed when ab=ag conc.

Front 72

Where do antibodies of the ABO system come from?

Back 72

These serum antibodies (usually IgM) occur naturally in respones to similar carbohydrate structures on normal GI flora

Front 73

What kind of serum antibody will you find a patient with 00 blood?

Back 73

Anti-A, Anti-B

Front 74

What kind of serum antibody will you find a patient with AA, AO blood?

Back 74

Anti-B

Front 75

What kind of serum antibody will you find a patient with BB, BO blood?

Back 75

Anti-A

Front 76

What kind of serum antibody will you find a patient with AB blood?

Front 77

When are anti-Rh antibodies produced?

Back 77

only when an Rh- individual is exposed to Rh+ RBC

IgG

Front 78

What type of hypersensitivity reaction is a transfusion reaction?

Back 78

Type II Hypersensitivity

Pentameric IgM ab agglutinates RBCs; IgM also is good activator of the classical pathway of complement

Front 79

When is Rh+ compatibility a major concern?

Back 79

Pregnancy; A pregnant RhD- woman w/ RhD+ baby can have a reaction during delivery and form anti-RhD IgG antibodies, which can cross the placenta and cause hemolytic diseaes of the newborn in subsequant RhD+ babies

Front 80

What would a lack of transferrin result in?

Back 80

Atransferrinemia; severe anemia w/ iron overload in non-hematopoietic tissues

Front 81

What two molecules make up Heme?

Back 81

Fe-protoporphyrin IX

Front 82

Reticulocytes

Back 82

Immature RBCs

Front 83

How is protein biosynthesis in reticulocytes regulated?

Back 83

Heme levels activate heme kinase

Front 84

How will high levels of heme affect protein biosynthesis in reticulocytes

Back 84

Increase protein biosynthesis (alpha, beta globins)

Front 85

How will low levels of heme affect protein biosynthesis in reticulocytes?

Back 85

Decreased protein biosyntheis (alpha, beta globins)

Front 86

What is porphyria?

Back 86

Disease caused by metabolites of the heme synthesis pathway, which accumulate and cause toxic effects w/ incomplete heme synthesis

Front 87

Porphyria Pathway

Back 87

Glycine + Succ-CoA -> delta-ALA -> porphobilinogen -> (lots of porphyrins) -> porpphyrins -> protophyrin IX -> heme

Front 88

What does the chrome in cytochrome indicate?

Back 88

Heme; it's a part of CYP450; so things that induce CYP450 deplete heme stores, so the heme synthesis ramps up

Front 89

Acute Intermittent Porphyria

Back 89

AD enzyme activity which is usually enough to get by; but in things which induce CYP450 or other cytochromes (which depletes heme), most common porphyria

Front 90

Myoglobin

Back 90

Intracellular 02 storage protein

Front 91

When does myoglobin release 02?

Back 91

Low P02, indicating 02 deprivation

Front 92

How does oxygen binding change the stereochemical configuration o fheme?

Back 92

Oxygen binding pulls electrons from the iron and reduces its ionic radius, allowing it to move into the plane of the porphyrin ring. This pulls the proximal histidine (and the helix it belongs to), triggering a conformational rearrangement in the protein

Front 93

What is the source of 2,3-BPG in RBCs?

Back 93

2,3-BPG shunt

Front 94

What is the function of 2,3-BPG

Back 94

Allosteric effector of deoxygenated hemoglobin (in tissue); promotes the release of remaining oxygen molecules to tissues that need it most (increases in individuals living at high altitudes or chronic hypoxia) - increases the net delivery of oxygen per hemoglobin molecule

Front 95

Which hemoglobin configuration is the low oxygen affinity state?

Back 95

T State; Deoxyhemoglobin

Front 96

Which hemoglobin configuration is the high oxygen affinity state?

Back 96

R State; Oxyhemoglobin

Front 97

Oxygen Binding Regulators; they're all negative regulates of 02 binding to heme

Back 97

2,3 BPG
C02
Hydrogen Ion
Chloride Ion

Front 98

What is the molecular basis of the Bohr effect?

Back 98

Protonation of Hb stabilizes the T-state (deoxyhemoglobin), promoting oxygen release in the tissue beds

Front 99

What is the molecular basis for the left shift of the oxygen dissociation curve for fetal and embryonic hemoglobin?

Back 99

Gamma subunits of HbF/E has a lower affinity for 2,3 BPG (and thus stronger oxygen binding)

Front 100

A 35-year-old man is brought to the ER after severing his right femoral artery in a woodshop accident. The patient requires a blood transfusion. Due to a blood shortage, however, the physician has no other recourse but to use outdated blood for the transfusion. Immediately following the transfusion the patient begins to show signs of hypoxia, slips into a coma, and dies. What happened?

Back 100

the half life of 2,3-BPG in RBCs is about 6 hours