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Flashcards in MCM Final Part 2 Deck (200):
1

RBC

non-nucleated, biconcave shape
Lack organelles
Consist only of plasma membrane, cytoskeleton, hemoglobin, and glycolytic enzymes

2

Spectrin

A large dimeric protein consisting of two polypeptides
The two polypeptides associate in antiparallel pairs to form a rod
Two chains joined head to head form tetramer, found at cortical region of RBC

Make RBC more rigid

3

Elliptocytosis

Autosomal dominant
Characterized by presence of oval-shaped RBCs
Caused by defective association of spectrum subunits, defective binding of spectrum to ankyrin, protein 4.1 defects, and abnormal glycophorin
Anemia, jaundice, splenomegaly

4

Spherocytosis

Autosomal dominant
Condition involving a deficiency in spectrin
RBC are spherical, of different diameter and many of them lack the typical central pale area
Anemia, jaundice, splenomegaly

5

G6PD deficiency

G6PD protects membrane and hemoglobin from oxidant damage

Frequent metabolic cause of intravascular hemolysis caused by severe infection, hepatitis or diabetic ketoacidosis

6

Sickle cell anemia

Point mutation in which val converted to glutamic acid in 6th position of beta-globing chain
Causes aggregation, formation of sickle cell RBC
Severe chronic hemolytic anemia and obstruction of post capillary venules

7

Thalassemia syndromes

heritable anemias characterized by defective synthesis of either the alpha or beta chain of the normal hemoglobin tetramer

8

Neutrophils

50-70%
migrate to sites of infection where they recognize and phagocytose bacteria

9

Lymphocyte

20-40%
B cell, T cell, Natural killer cells

10

Monocyte

2-8%
Largest
Travel bloodstream enter peripheral tissues and transforming macrophages

11

Eosinophil

1-5%
Eosinophil peroxide (EP): binds microorganisms and facilitates killing by marcophages

Major basic protein: binds to and disrupts membranes of parasites

Eosinophil cationic protein (ECP): neutralizes heparin, together w/ MBP causes fragmentation parasites

12

Basophil

1%
Contains large cytoplasmic granules w/ sulfated or carboxylated acidic proteins like heparin
Express IgE receptor on surface
Release histamine to mediate allergic reactions

13

Acute Leukemias

consist of massive proliferation of immature cells w/ respect to bone marrow cells and rapid progression of the disease

Acute lymphoblastic leukemia (ALL): when derived from lymphoid cells
-mainly affects children

Acute myeloblastic leukemias (AML): when derived from myeloid, erythroid and megakaryocytic cell progenies
-affects adults

14

Anemia

depletion of red blood cell formation

a reduction of total circulating red cell mass below normal limits

-Iron
1. heme
2. chronic blood loss, dietary, prematurity
3. microcytic anemia, hypochromic anemia

-Folate
1. DNA synthesis
2. Dietary, liver cirrhosis
3. megaloblastic macrocytic anemia

-B12
1. DNA syntehsis
2. dietary or vegetarianism, impaired absorption of intrinsic factor (pernicious anemia)
3. megaloblastic macrocytic anemia or pernicious anemia

15

Infections

determined by a decline in the formation of normal leukocytes

16

Bleeding

a reduction in the number of platelets

17

Chronic leukemias

are classified as lymphocytic myeloid or hairy cell type leukemias

They are characterized by a lesser production of immature cells and slow progression of the disease

18

Chronic lymphocytic leukemia (CLL)

observed main in adults (50 or older)

Predominatn proliferation of B cells and a large number of abnormal lymphocytes in peripheral blood

Lymphoadenopathy and splenomegaly

19

Chronic myeloid leukemia (CML)

Regarded as a myeloproliferative condition (proliferation of abnormal bone marrow stem cells)

Affects adults

Hepatosplenomegaly and leukocytosis (excessive myelocytes, metamyelocytes and neutrophils in peripheral blood)

After chronic phase for 5 years, disease changes into an acute leukemia requiring stem cell bone marrow transplantation

Philadelphia chromosome
-reciprocal translocation between long arms of chr9 and chr22
-fusion of abl/bcr encodes tyrosine kinase --> neoplastic phenotype

Imatinib inhibits kinase

20

Hairy cell leukemia (HCL)

rare type B cell leukemia
The cells look hairy because of multiple thin cytoplasmic projections

Splenomegaly, lymphadenopathy, and recurrent infections

Relationship between HCL and exposure to herbicide agent Orange

21

Leukocyte adhesion deficiency type I (LAD I)

caused by a defect of the beta2 subunit (aka CD18) present in LFA-1 and MAC1

so Neutrophils are unable to leave blood vessels because of defect in the recruitment mechanism

LFA-1 and MAC1 are required for binding to endothelial ICAM, for trans endothelial migration

In these patients, inflammatory cell infiltrates are devoid of neutrophils

Delay in separate of umbilical cord at birth is an indication of LADI

22

Leukocyte adhesion deficiency Type II (LAD II)

The fucosyl-containing ligands for selection are absent due to a hereditary defect of endogenous glucose metabolism

Have reduced intrauterine and postnatal growth and severe mental retardation

23

Leukocyte adhesion deficiency type III (LAD III)

determined by mutations in kindlin (associated with intracellular domain of beta integrin subunit)

24

Eosinophilic esophagitis

including dysphagia and abdominal pain

correlates with the increase of eosinophils in the esophageal mucosa

dysregulated eosinophilia appears to depend on excess production of IL5 and IL13 by TH2 cells and presence of chemoattractant chemokine ligand 26 in the inflammatory area of esophagus

Fungal and insect allergens appear to trigger eosinophilic esophagitis

Treatment: steroids

25

Platelet formation

Megakaryocytic develop cytoplasmic projections that become proplatelets which fragment into platelets

Platlets bind and degrade thrombopoietin, a mechanism that regulates platelet production



26

Thrombocytopenia

A reduction in number of platelets in blood leads to increased susceptibility to bleeding and increased morbidity and mortality due to bacterial or fungal infections

Defined by a decrease in number of platelets to less than 150,000 uL of blood

1. Caused by decrease in the production of platlets
2. An increase in the destruction of platelets
3. Aggregation of platelets in the microvascualture

27

Thrombocytosis

defines an increase in the number of platelets circulation gin blood

28

Microfilaments

Actin: Least stable
Control cell behavior

Composed of TWO strands of actin

Fxns: cytokinesis, ameoboid movement, changes in cell shape, endo/exo cytosine, cell contractility, mechanical stability

Flexible and relatively strong

Phalloidin: targets actin

29

Microtubules

Tubulin: More stable
Establism polarity
MTOC

30

Intermediate filaments

Most stable
Mechanical strength
Desmosomes

Keratins

31

Microtubule Organzing Center (MTOC)

Two main functions
1) organization of eukaryotic flagella and cilia (motion)

2) organization of the mitotic and meiotic spindle apparatus (mitosis/ meiosis)

32

Keratins

Impart mechanical strength

Anchor intermediate filaments at site of cell-cell contacts:
-cell-cell contacts (desmosomes)
-cell-matrix contacts (hemidesmosomes)

33

Desmosomes (aka macula adheres)

Specialized cellular structures

Mediate cell-to-cell adhesion

Multiple-protein complex
Consisting of Cell adhesion protein/Linking proteins

Attach cell surface adhesion proteins to intracellular keratin cytoskeletal filaments

Link to keratin through specific proteins like desmoplakin

Cell adhesion proteins: desmocollin, plakophillin plakoglobin

Also serve as scaffold for signaling molecules that respond to cells coming together

34

Phalloidin

Toxin from Death Cap mushrooms
Targets Actin
Binds to Actin (tight & specific)
Fluorescently tagged phalloidin used in imaging actin in cells (melanoma)

Visualizing loose actin bundles in cancer cells

35

What controls cell behavior

Actin polymerization

36

Actin Polymerization

Controls cell behavior

Filopodia
Lamellipodia
Pseudopodia

37

Filopodia

micro spikes
one dimensional
found in fibroblasts

38

Lamellipodia

Two dimensional
Sheet like structures
Formed by epithelial cells and fibroblasts, some neurons

39

Pseudopodia

Three dimensional projections filled with an actin-filaments, found in neutrophils

40

Actin Filaments

Accumulate at cell periphery
Determine the shape and movement of cells

41

ARP Complex

Actin Related Protein (ARP)

Assists w/ nucleation of Actin filaments

ARP proteins mimic actin and serve as sites of nucleation for different directions of actin polymerization

Forms new actin nucleation core from actin monomers, the ARP2/3 binds existing actin filaments so can grow on old one

Different ARP family members and actin associated proteins that drive deb ranching
1) Coronin: can do debranching and depolymerization
2) GMP: only does deb ranching

Point: a lot of actin binding proteins that go into whole process

42

Listeria Monocytogenes

In the soil/ fresh produce

Invades intestinal cells
Immuncompromised at risk (elderly)

Attaches to receptors on enterocytes
Mimics accessory (ARP) proteins that nucleate actin monomers

Surface protein ActA activates ARP 2/3 complex

Activates ARP2/3 complex to trick you cells into rearranging and becoming leaky
-Actin polymerization the propels the bacterium unidirectionally into the host cell membrane

Listeria --> moves through cells like speed boats
Growing filaments are driving force

43

Myosin Motor

Actin-binding and ATPase domains

Myosin II heads provide the driving force in movement

ATP drives the movement of myosin heads along actin filament

Carries vesicles from ER to golgi to get glycosylation
Move all kinds of things around
Burn a lot of ATP

44

Anchoring junctions

Holds cells together

Actin filament attachment sites
-cell-cell junctions (adherens junctions)
-Cell-matrix junctions (actin-linked cell-matrix adhesions)

Intermediate filament attachment sites
-cell-cell junctions (desmosomes)
-cell-matrix junctions (hemidesmosomes)

Cell-Cell uses cadherin
Cell-matrix uses integrin

45

Occluding junctions

Separates apical and basolateral

Tight junctions

46

Channel forming junctions

Allows cell communication

Gap junctions

47

Signal-relaying junctions

Neuromuscular junction

Chemical synapses

48

Adherens Junctions

Type of Anchoring Junction
-Cell-cell

Cadherins, catenins and actin

alpha-catenin, beta-catenin, plakoglobin (gamma catenin), p120 catenin, vinculin, alpha-actinin

49

Desmosome

Type of Anchoring Junction
-Cell-Cell

Desmosomal catherine and intermediate filaments
Plakoglobin, plakophilin, desmoplakin

50

Cell-Matrix Junction

Actin linked cell matrix adhesion or hemidesmosomes

Talin vinculin, alpha-actinin, filamin, paxillin, focal adhesion kinase (FAK), pectin dystonia

51

Non classical cadherins

desmocollins and desmogliens --> desmosomes

52

Classical cadherins description

Ca2+ dependent adherens junctions
E-cadherin: epithelial cells and brain
N-cadherin: muscle, nerve, Lens cell, fibroblasts
P-cadherin: placenta and epidermis

53

Classical Cadherins chart

E, N, VE, P
Homo
Adherens junctions

54

Desmosomal Cadherins Chart

Desmoglein Desmocollin
Homo
Desmosome

55

Ig fmaily chart

NCAM, I CAM
Both
Neuronal synapses

56

Integrins (chart

Hetero
Focal adhesion
Hemidesmosomes

57

Heart-Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

patients with missence mutations in desmocollin-2

Common cause of sudden death in young males

Desmocollin not properly inserted into membrane

58

Multiple Blistering Disorder
phephigus foliates

Auto immune response
auto antibody mediated blistering disease in which antibodies against desmoglein 1 cause loss of adhesion of keratinocytes in the superficial layers of epidermis

59

Functions of Tight junctions

1) seals apical membranes, cell polarity

Recruit cytoskeleton
Recruit signaling molecules
Form barrier between apical and basolateral side of cell
Vectorial transfer: stuff goes high concentration to low concentration

60

Gap Junction

primarily made of two proteins connexions and innexin

Pores: composed of six subunits calle connexions

Will close upon stress and leakage

61

Focal Contacts

Integrin mediated
Active via kinases and actin nucleatinon
Bind ECM proteins (laminin, fibronectin, elastin collagen)

Integrin containing multi-protein complexes transmit mechanical force --> mechanical linkage to ECM

Transmit regulatory signals between ECM and epithelial cell

62

Integrins

Bind stuff the ECM is laced with

63

Inside-Out signaling

Inactive integrin (bent)
Intracellular signals bind talin to beta su tail
relaxes leg restraints further unbending

64

Outside-In Signaling

unbent integrin bound by ligand
FAK

ligand to intern stimulates conformational changes, activate focal adhesion kinase (FAK)
FAK is then autophosphorylated on tyrosine near catalytic domain which binds Src.

FAK contains central kinase
interacts w/ a lot of things
-ARP2/3 which is regulated by WASP, initalies polymerization of new actin filament

FAK also influences actin contraction and polarization through another GTPase Rho

65

Steps in Collagen Biosynthesis

In Lumen of ER

Hydroxylation of proline and serine residues; glycosylation of selected hydroxylsine resides

66

FACIT collagen

holds collagen together
non-fibrillar collagens
attach to surface of fibrillar collagens

67

Collagen assembly enzymes

Prolyl hydroxylase or Lysyl hydroxylase

Cofactor: ascorbate

By product: succinate

68

Scurvy

Loss of cofactor
ascorbate or iron

Problem w/ hydroxylation of collagen

69

Marfan's syndrom

defect in elastin
weakened aorta

70

Ehlers- Danlos syndrome

mutated fibrous proteins or enzymes

Alter structure, production or processing of collagen

71

Cross linking of elastin

Lysyl oxidase

72

Olfactory receptors

One receptor type binds a single class of odorant (ligand)

G proteins activate adenylate cyclase produces cAMP opens specific sodium and calcicumion channels

Influx sodium and calcium
Depolarization
generates action potential

Action potential via axon to brain

73

Rho activation of Actin reorganization

stress fiber formation

Ligand binding (chemoattractant) front of cell stimulates GPCR --> G12/13 which activates Rho --> actin-myosin contraction


=Activation stays in rear

74

Rac activation on actin reorganization

lamellipodia
shattered glass

Ligand binding front of cell stimulates
GPCR --> Gi --> generates PIP3 which activates RAC

Rac activates ARP2/3 complex forms lamellipodia

activation dominates in the front

75

Cdc42 activation

filopodia
circle with little projections around

76

Stem Cell Factor (SCF)

starts things going
also known as c-kit ligand and steel factor
produced by fetal tissues and BM
weak stimulator of hemoatpoiesis
Makes stem cells responsive to other cytokines

77

Fit3 ligand

acts on pluripotent stem cells in synergy w/ TPO, SCF and interleukin

78

Erythropoieses

Proerythroblast
Basophilic erythroblast
Polychromatophilic erythroblast
Orthochromatophilic erythroblast
Reticulocyte
RBC

79

Proerythroblast

Large central nucleus
Bluest cell
Nucleus: and, fine chromatin,
Mitotic

80

Basophilic erythroblast

Smaller nucleus
Patchy chromatin **
Bluish clumps on pale blue
Nucleus: and, chromatin coarse
Mitotic

81

Polychromatophilic erythroblast

Smaller nucleus condensed chromatin
Blue clumps polyribosomes
Pink Hgb
cytosol: yellow pink with blue tinge
nucleus: checkerboard
mitotic

82

Orthochromatophilic erythroblast

dense eccentric, pynotic nucleus (dying, dark no light)

Cytoplasm pink w/ slight blue tinge
Nucleus off center

Not mitotic

83

Reticulocyte

nucleus extruded
blue polyribosomes

84

Myeloid cells

monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes

85

Lymphoid cells

t cells, b cell natural killer cells

86

Leukopoiesis

results in formation of cells belonging to the granulocytes and granulocyte series

87

Agranulopoises

Lymphocytes, monocytes

heterochromatin content increases
no specific granules form
no nuclear lobulation
cell size decreases

88

Granulopoiesis

Neutophils, basophils, eosinophils

Chromatin condenses
cytoplasmic granules form
nucleus becomes lobulated
cell size decreases

89

Leukopoises: Granulocytes

Myeloblast
Promyelocyte
Myelocyte
Metamyelocyte
Band or Stab
Segmented neutrophil

90

Myeloblast

Large round euchromatic nucleus
No cytoplasmic granules
Mitotic
cytoplasm: sm blue clumps on it
Nucleus: red-blue, and, fine 2-3 pale nucleoli

91

Promyelocyte

Large flattened nucleus
Azurophillic granules present
Cytoplasm: bluish, many sm azurophil granules
Nuc: red-blue and, chromatin more coarse

92

Myelocyte

Golgi region (light area w/o nucleus)
Slightly indented nucleus
specific granules

93

Metamyelocyte

Golgi actually indents nucleus
no mitosis

94

Band or Stab

Horse-shoe shaped nucleus

95

Segmented neutrophil

mature cell
segmented nucleus

96

Leukopoisesis: agranulocytes


Monoblast
Promonocyte
Monocyte
Marcophage

97

Monoblast

large round nucleus
no granules
identical to myeloblast

98

Monocyte

Mature cell
Nucleus indentation u shape irregular
cytoplasm: foamy

99

Macrophage

monocytes that migrated to tissue

100

totipotency

ability to a cell to give rise to all cells of an organism, including embryonic and extra embryonic tissues

A zygote

101

Pluripotency

ability of a cell to give rise to all cells of the embryo and subsequently adult tissues

embryonic stem cells

102

Multipotency

ability of a cell to give rise to different cell types of a given lineage

Adult stem cells

103

Transit amplifying cells

cells the divid frequently

Transit from a cell with stem cell characteristics to a differentiated cell

Leave basal layer and incorporate into the layers above

Programmed to have limited number of divisions

104

Maintenance of Stem Cells

For a steady pool of stem cells, 50% of daughter cells must remain as stem cells

Divisional asymmetry

Environmental asymmetry

105

Divisional asymmetry

asymmetric division may create 2 cells, one with stem cell characteristics and another with factors that give it ability to differentiate

One with localized determinant stays a stem cell

106

Environmental asymmetry

division makes 2 identical cells but environment may influence/ alter 1 cell

107

embryonic stem cells

pluripotent

sperm + egg does fertilization forms zygote (totipotent) which forms blastocyst with inner cell mass (pluripotent) can go on to fetus

or inner cell mass can be extracted for ES

Proliferating indefinitely in culture
Unrestricted development potential
Different cell types

108

adult stem cells

multipotent
undifferentiated and generate cell types in the tissues in which they reiside

109

Pluripotent transcription factors

Nanog, Oct4, Sox2 and FoxD3

110

Induced Pluripotent stem cells

Adult fibroblasts can be reprogrammed to induce pluripotent stem cells by the introduction of a defined and limited set of transcription factors Oct3/4, Sry, Sox2, c-Myc, Klf4, n-Myc, Lin28 and Nanog

111

IPS combinations

Oct3/4, Sox2, c-Myc, Klf4

Oct 3/4, Sox2, Klf4

Oct3/4, Sox2, N-Myc, Klf4

Oct3/4, Sox2, Lin28, Nanog

112

Somatic Cell Nuclear Transfer

Egg cell w/o nucleus + somatic cell (any cell in body other than egg or germ cell) --> fusion

Stimulate cell division process
Get a bunch of fusion cells

Forms blastocyst

Extract inner cells mass --> culture pluripotent embryonic stem cells

113

SCNT challenges

Inefficient (may need hundreds of oocytes)

Technically demanding

114

Growth factors found in pluripotent cells

Cripto & GDF-3

115

Embryonic hemoglobin

delta epsilon
alpha epsilon
delta gamma

116

Fetal hemoglobin

alpha gamma

117

Adult

alpha beta

118

Hemoglobin (Hb)

four globular subunits
each bound to an iron contains heme
heme has a heterocyclic porphyrin ring with iron present at center

Rings: four 5-membered rings containing nitrogen connected by single carbon bridges

119

Biosyntheis of Heme
Phase I

Mitochondrial

Generation of aminolevulinic acid (ALA)

ALA from glycine and succinyl coA
ALA synthase
Needs pyridoxal phosphate (Vitamin B6)

Inhibited by heme and heparin

mRNA contains iron response elements, responds by inhibiting transcription

PXR activation induces expression of ALAS mRNA

120

Biosynthesis of Heme
Phase 2

Cytosol
condensation of two delta ALA leading to porphobilinogen and then the use of four porphobilinogens to assemble the terapyrrole ring system

121

Biosynthesis of Heme
Phase 3

Mitochondria
Two oxidation reactions of coproporhyringoen III to instal the side chain vinyl groups in ptotoporphyringen IX

Installation of Fe2+ by ferrochelatase gives heme

122

Important rate limiting set and what does it need

ALA synthase
Vit B6 (pyridoxal phosphate)

123

What installs Fe2+ in ring

Ferrochelatase

124

What inhibits phase I

Heme
Hemin

125

Acute intermittent porphyria

Hepatic
Porphobilinogen deaminase step

accumulation of ALA and PBG

126

Congenital erythropoietic porphyria

Erythocyte derived
Uroporphyrinogen III synthase deficiency

Autosomal recessive

accumulation of uroporphyringoen I --> red colored air oxidation product uroporphyrin I

Photosensitivity: red color in urine and teeth

127

Porphyria cutanea tarda

Hepatic & erythrocyte derived
Most common

Uroporphyrinogen decarboxylase

Cant form coproporphyringen III

accumulation of uroporphyrinogen III --> uroporphyringoen I

red wine urine
photosensitivity

128

Variegate prophyria

Hepatic
Protoporphyrinogen IX oxidase

129

What inhibits ferrochelatase

Lead

130

Heme to biliverdin

heme oxygenase

131

Heme oxygenase

liberates one of the carbon bridges as carbon monoxide (CO), converts ferrous iron (Fe2+) into ferric ion (Fe3+) to get green biliverdin

132

Heme breakdown steps

1) Heme --> biliverdin (heme oxygenase) green

2) biliverdin --> bilirubin (bilirubin reductase) red-orange chews up NADPH

3) Bilirubin in liver (UDP-glucuronosyl transferase)
-unconjugated indirect
-conjugated direct

4) Conjugated Bilirubin --> small intestine

5) BR to urobilinogen (microbial reduction) colorless

6) urobilinogen --> stercobilin ( red-brown)
or urobilinogen--> urobillin (yellow of urine)


133

Bilirubin is direct once

its conjugated with glucuronic acid
making it soluble

134

Jaunice

Jaundice: Hyperbilirubinemia

Pre-hepatic
-Increased unconjugated BR
-Normal ALT & AST
-No conjugated BR in urine

Intra-hepatic
-Increased unconjugated & conjugated BR
-Increased ALT & AST
-Conjugated BR in urine

Post-hepatic
-Increased conjugated BR
-Normal AST & ALT
-Conjugated BR in urine (dark urine)

135

Neonatal jaundice

due to elevated levels of un-conjugated bilirubin

physiological jaundice

Deficiency in UDP-GT enzyme

136

Crigler-Najjar syndrom

deficiency of UDP-GT

Severe hyperbilirubinemia

BR accumulates in brain of babies

137

Gilbert Syndrom

common, benign disorder
Reduced activity of UDP-GT

138

Hepatitis

inflammation of the liver
leads to liver dysfunction
increased levels of unconjugated and conjugated BR in blood

BR accumulates in skin and sclera of eyes, yellow discoloration,
Dark tea colored urine

139

2,3 BG affect on dissociation curve

shifts right
decrease affinity

140

pH affect on dissociation curve

shifts right
decrease affinity

141

HbF affect on dissociation curve

shifts left
increase in affinity over mother Hb

142

Iron transport to blood

ferroportin

143

Carries iron to BM

trasferrin

144

Hereditary Hemochromatosis

organ dysfunction due to iron overload

mutations in HFE gene

145

Regulator of iron homeostasis

Hepcidin
peptide made by liver

binds to ferroportin and causes internalization of ferroportin is destroyed by proteolysis

Iron high -> hepcidin expression up

146

Vitamin B12

removes methyl group from N-methy THF to release THF

147

Megaloblastic anemia

Vitamin B12 deficiency or folate def
-result of diminished synthesis of DNA in developing RBC

large RBCs
normal hemoglobin content relative to size

148

Pernicious anemia

vitamin B 12 deficiency occur due to lack of intrinsic factor
fatal outcome in 1900
This is a megaloblastic microcytic anemia

149

Schilling test

part 1:
oral dose B12
urine collected look for B12
if absent --> cobalamin not absorbed pernicious anemia
if present --> normal

part 2:
oral dose B12 plus intrinsic factor
urine collect
if radioactive B12 present: pernicious anemia due to lack of intrinsic factor

150

Function erythrocytes

carrying O2 from lungs
carrying co2 from body
acid/base buffering

151

Last cell type to mature upon entering circulation

reticulocyte

152

Kicks starts erythropoietin

Hypoxia inducible factor

153

Iron in tissues

transferred between ferritin and hemosiderin

154

Iron in plasma (carry to bone marrow)

transferrin

Fe3+ form

155

Iron in RBC

hemoglobin

156

Non heme iron

goes from 3+ charge to 2+ charge

157

Hypochromic anemia

deficiency in transferrin

158

Each gram of hemoglobin combines with

1.34 mL oxygen

159

Average male 15g hemoglobin per 1 dL blood

How many mL of O2 can be carried

20.1 mL O2/dL blood

160

Oxygen saturation left shift

greater affinity of blood for oxygen
pulmonary capillaries normal

Polycythanemia and methemoglobina

161

Oxygen saturation right shift

Anemia

162

Oxygen capacity

maximum amount of oxygen that can be carried by hemoglobin in blood

20.1 mL O2/dL blood

163

Oxygen content

how much oxygen is actually being carried by the blood (how many honeybees present)

19.5 mL O2/dL blood

164

Oxygen saturation

spots occupied by O2 as a percentage of total available spots

ratio of how many honeybees are carrying spore to total honey bees present

165

ATP

maintains iron in Fe2+ rather than Fe3+

166

Polycythemia primary

Primary

Genetic low EPO
extra RBC
increase total blood volume
increase viscosity
normal cardiac output

167

Polycythemia secondary

hypoxia (high EPO)
extra RBC cardiac out may be abnormal

168

Polycythemia physiological

high altitude adaption
extra RBC
normal cardiac output

169

Methemoglobinemia

Increase met-hemoglobin
Iron is in ferric form
decreased oxygen availableilty to tissues

Leftward shift of oxygen hemoglobin disassociation curve
-increase in affinity of blood for oxygen

blood chocolate colored
caucasian skin appears blue

170

Chemotaxis

GTPase family

Rho family

171

Qiescent cells

actin is actively maintaining a resting state (not static)

172

Hematopoietic growth factors

CSF
Erythropoietin and thrombopoietin
Cytokines

173

Erythropoietin

produced primarily in the kidneys
stimulates formation of RBC
Chronic renal disease--> anemia decrease EPO
Main trigger hypoxia
When treating look for reticulosite

174

Thrombopoietin

produced in liver
stimulates an increase in megakaryocytic and platelets

175

ES + retinoic acid, insulin, thyroid hormone

adiopocyte

176

ES + retinoid acid

neuron

177

ES+ macrophage colony stimulation factor, IL3, IL1

macrophage

178

ES + dibutyryl cAMP and retinoic acid

smooth muscle cell

179

ES + fibroblast growth factor, epidermal growth factor, platelet derived growth factor

astrocytes and oligodendrocytes

180

Neuron

retinoic acid

181

Smooth muscle cell

dibutyryl cAMP, retinoic acid

182

Adipocyte

retinoic acid and insulin, thyroid hormone

183

Astrocytes and oligodendrocytes

Fibroblast growth factor, epidermal growth factor, platelet growth factor

184

Macrophage

macrophage colony stimulating factor, IL3, IL1

185

Neural stem cells

can adjust behavior and function to match their location

186

Heme iron

Fe2+ most easily absorbable form of iron
Once heme enters enterocyte, it is converted to ferric iron (Fe3+)
Ferritin bonds to and stores iron in the ferric form
When ferritin degraded, turns into hemosiderin

187

Non Heme iron

enters at Fe3+, converted to ferrous Fe2+ by ferric reductase (need Vit C)
Fe2+ enters enterocyte and converted to ferric iron for storage or exported out of enterocyte by ferroportin

188

Hfe

regulates hepcidin expression

normally Hfe binds Tfr2 in hepatocytes and stabilizes it, iron normally transferred to TfR2 which drives expression of hepcidin

if mutated cannot bind to TfR2
cannot turn on hepcidin

189

Folate Metabolism

1) main carbon transfer occurs when the carbon side chain of serine is transferred to THF to form N-methylene-THF

2) The carbon of N-methylene-THF is then transferred to deoxyuridylate (dUMP) to form deoxythymidylate (dTMP) during which dihydrofolate (DHF) is made

3) DHF is reduced by dihydrofolate reductase to form THF start cycle again

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Need for B12

N-methylene-THF will not give up single methylene group to dUMP to make dTMP for DNA synthesis

An N-methylene-THF needs to be de-methylated to enter folic acid cycle as THF

Vit B12 removes methyl group from N-methylene-THF to make methyl-cobalamin (B12-CH3) and release THF

Then cobalamin transfer methyl group to homocysteine to create methionine using methionine synthase

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B12 deficiency

Rare

If occurs due to loss of intrinsic factor

Pernicious anemia

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Intrinsic factor

made by parietal cells of stomach

intrinsic factor carries B12 to ileum where receptors bring into body

193

Stimulates EPO production

Anemia
Decrease in renal blood flow
Central hypoxia

194

Deficiency in iron

microcytic anemia

195

Ferritin

stored in cell Fe3+

196

Ferroportin

receptor move ferritin (w/ Fe3+) into plasma

197

Transferrin

Once in plasma circulates as transferrin

198

Hypochromic anemia

deficient transport of transferrin

199

Absorption of iron enhanced by

Ascorbate 2 (Vit C)

200

Absorption of iron impaired by

hepcidin, phytates (grains), tannins (wine) and antacids