Week 3 Flashcards
1
Q
Composition of blood
A
- Plasma
2. Formed elements (WBCs, platelets, RBCs)
2
Q
Functions of blood
A
- Delivery of nutrients and oxygen
- Waste removal
- Homeostasis
- Immune function
3
Q
Function of erythrocytes
A
CARRY OXYGEN
4
Q
Hematocrit
A
Percentage of blood that is cells
5
Q
What stimulates erythropoiesis?
A
Tissue hypoxia, espeically low O2 delivery to kidney
6
Q
HIF
A
Accumulates in kidney during hypoxic conditions; ubiquitinated with normal oxygenation
7
Q
How does erythropoietin act on erythroid lineage?
A
- Increase stem cell differentation to erythroid lineage
2. Increase rate of RBC maturation
8
Q
Role of Iron in RBC production?
Cause of deficiency?
Consequence of deficiency?
A
- formation of heme
- blood loss
- microcytic anemia
9
Q
Role of Vitamin B12 in RBC production?
Cause of deficiency?
Consequence of deficiency?
A
- DNA synthesis
- Loss of intrinsic factor (pernicious anemia)
- macrocytic anemia
10
Q
Role of Folate in RBC production?
Cause of deficiency?
Consequence of deficiency?
A
- DNA synthesis
- High heat cooking, alcohol consumption
- macrocytic anemia
11
Q
Oxygen capacity
A
How much O2 can be carried by heme
Calculation: 1.34 mL O2/g Hb x [Hb]
12
Q
Oxygen content
A
How much O2 is being carried by heme
Calculation: O2 capacity x O2 saturation
13
Q
Oxygen saturation
A
% available spots on heme with O2 bound; given by pulse oximetry
14
Q
How is ATP gained and used by RBCs?
A
Anaerobic glycolysis; membrane flexibility, ion transport, maintenance of ferrous iron, prevention of Hb oxidation
15
Q
Consequence of RBC not getting enough ATP?
A
Hemolysis; RBC lifespan of ~120 days
16
Q
Fate of “old” RBCs
A
filtered out (hemolysis) by spleen
17
Q
Fate of “old” Hb
A
Peptide chains broken down to AAs, Heme broken down by bilirubin, Iron recycled for new heme
18
Q
Anemia
A
Too few RBCs; O2 capacity and content reduced, blood viscosity reduced, heart workload increased
19
Q
Polycythemia
A
Too many RBCs; O2 capacity and content increased, blood viscosity increased, heart workload increased
20
Q
Primary polycythemia
A
Due to abnormally high activity of bone marrow in RBC production; low EPO levels
21
Q
Secondary polycythemia
A
O2 low due to altitude or lung/heart disease; EPO levels high, heart or lungs may be abnormal
22
Q
Physiologic polycythemia
A
Due to altitude change in environment; EPO levels high
23
Q
Porphyrin ring structure of heme
A
four 5-membered rings with Fe2+ present
24
Q
Phase I of Heme biosynthesis
A
In mitochondria; Succinyl CoA + Glycine = ALA
Enzyme: ALA synthase
25
Phase II of Heme biosynthesis
In cytosol; ALA becomes Porphobilinogen, porphobilinogen becomes hydroxymethylbilane
Enzymes: ALA dehydratase, phorphobilinogen deaminase
26
Phase III of Heme biosynthesis
In mitochondria; Protoporphrinogen IX becomes Protoporphyin IX, Protoporphyrin IX becomes heme
Enzymes: Protoporphyrinogen oxidase, Ferrochelatase
27
Acute Intermittent porphyria
Hepatic; defect in porphobilinogen deaminase
28
Congenital erythropoietic porphyria
Erythropoietic; defect in uroporphyrinogen III synthase
| Red color in urine, teeth, skin photosensitivity
29
Porphyria cutanea tarda
Hepatoerythropoietic; defect in Uroporpyinogen decarboxylase
30
Variegate porphyria
Hepatic; defect in protoporphyinogen IX oxidase
31
Heme oxygenase
Removes bridge between pyrrole rings of heme; O2 required; Biliverdin synthesized
32
Biliverdin reductase
Removes double bond from Biliverdin and adds H; NADPH required; Bilirubin synthesized
33
Bilirubin transport to liver
Bound to albumin as it is insoluble/indirect/unconjugated
34
UDP glucuronyl transferase
Conjugates free bilirubin 2x in liver
35
Urobilinogen
Either absorbed in kidney and oxidized to urobilin or moved to colon and metabolized to stercobilin
36
Pre-hepatic jaundice
Due to increased production of unconjugated BR; elevated levels of unconjugated/direct BR in blood; direct BR absent in urine
37
Intra-hepatic jaundice
Impaired hepatic uptake, conjugation, or secretion of conjugated BR; hepatic dysfunction; increased unconjugated and conjugated BR, increase in ALT, AST, conjugated BR in urine
38
Post-hepatic jaundice
Problem with BR excretion; elevated blood levels of conjugated BR; conjugated BR in urine (dark), no stercobilin in feces (pale)
39
Neonatal jaundice
Physiological; due to breakdown of HbF as it is replaced with HbA or immature hepatic metabolic pathway/UDP-GT enzyme deficiency
40
Criggler-Najjar Syndrome
Type I: complete absence of UDP-GT gene; causes kernicturus and brain damage-BR accumulates in brain
Type II: benign, mutation in UDP-GT gene; enzyme has less activity
41
Gilbert Syndrome
Relatively common, benign disorder - reduced activity of UDP-GT
42
Hepatitis
Inflammation of liver leading to dysfunction; caused by viral infections (A, B, C); increased levels of direct and indirect BR in blood; yellow discoloration, dark urine
43
Hereditary Spherocytosis
Autosomal dominant disorder where RBCs are spherical, not biconcave; more fragile - results in hemolytic anemia
44
General structure of Hb
Tetramer with 2 alpha and 2 beta globin chains; 8 helical segments; contains heme with ferrous Fe
45
HbF
Fetal hemoglobin; alpha2, gamma2 chains; 0.5% expression
46
HbA, HbA2
Adult hemoglobin; alpha2,beta2 (97% expressed) or alpha2, delta2 (3% expressed)
47
Sickle Cell Anemia
HbS occurs at AA #6 on beta-globin chain; substitution of valine for glutamic acid; causes Hb polymerization and sickle shaped RBCs - hemolytic anemia
48
B-Thalassemia
Underproduction of B chain; relatively common
49
2,3-BPG effect on ODC
Signal to Hb to let go of O2; reduces O2 affinity so Hb gives up more O2 to tissues; shifts curve RIGHT
50
pH decrease effect on O2 affinity
Decreases as pH decreases; favors release of O2; shifts curve RIGHT
51
HbF vs. HbA ODC
HbF will be shifted to the left due to HbF having higher affinity for O2
52
Pyruvate Kinase Deficiency
Build up of 2,3 BPG - problems with ODC and production of ATP; causes anemia
53
Ferritin
Responsible for storage of iron in liver
54
Transferrin
Carries iron to tissues where needed; 30% transferrin usually bound to iron
55
TIBC
Total Iron Binding Capacity; equivalent to transferrin levels; elevated in iron deficiency
56
Hereditary Hemochromatosis
Iron overload leading to organ dysfunction; shows up in 60s or later
57
Megaloblastic macrocytic anemia
Large erythrocytes; can be caused by B12 and folate deficiency, result of decreased DNA synthesis
58
Folate trap
Vitamin B12 required for demethylation of N-methyl-THF/DNA synthesis to occur
59
B12 Deficiency
Leads to macrocytic anemia; due to prevention of appropriate DNA synthesis
60
Intrinsic factor
Carries B12 to ileum where receptors can bring it into body; deficiency can result in pernicious anemia
61
Hematopoiesis in yolk sac
Weeks 3-8
62
Hematopoiesis in liver
Weeks 6-30
63
Hematopoiesis in spleen
Weeks 9-28
64
Hematopoiesis in bone marrow
Weeks 28-birth and into adulthood
65
Hematopoietic cell compartment
Vascular, contains hematopoietic stem cells
66
Marrow stromal compartment
Contains growth factors and source of energy to support hematopoietic stem cells
67
Hematopoietic stem cell
Capable of self-renewal; pluripotent - differentiate into myeloid or lymphoid lineages
68
Stem cell factor
Weak stimulator of hematopoiesis and makes stem cells responsive to other cytokines
69
Flt3 ligand
Stimilar to SCF, acts with other growth factors to commit to certain lineage
70
IL-3
Give rise to myeloid lineages
71
IL-1 and IL-4
Give rise to lymphoid lineages
72
IL-2
T cell growth factor
73
IL-2 and IL-6
B cell growth factor
74
GM-CSF
Stimulates formation of leukocytes and reticulocytes
75
G-CSF
Stimulates increase in neutrophils
76
M-CSF
Stimulates increase in monocytes
77
EPO
Produced in kidneys; causes formation of RBCs
78
TPO
Produced in liver; causes formation of platelets
79
Myeloid stem cells
Give rise to Monocytes, Neutrophils, Basophils, Eosinophils
80
Lymphoid stem cells
Give rise to lymphocytes
81
Granulopoeisis
Chromatin condenses, granules form, lobulated nucleus, cell size decreases
82
Agranulopoeisis
Heterochromatin increases, no granule formation, no lobulation of nucleus, cell size decreases
83
Neutrophils
Phagocytize bacteria, release antimicrobial chemicals
84
Eosinophils
Phagocytize Ag-Ab complexes, allergens, inflammatory chemicals; antiparasidic and bactericidal activity
85
Basophils
Secrete histamine, heparin; inflammatory reactions
86
Monocytes
Differentiate into macrophages, phagocytize pathogens, APCs
87
Self-renewal
Ability to reproduce self
88
Immortal Strand (hypothesis)
One daughter stem cell retains DNA preserved through generation; other daughter stem cell has newly synthesized DNA strand
89
Totipotency
Ability of cell to give rise to all cells of organism (embryonic and extraembryonic tissues); ZYGOTE
90
Pluripotency
Ability of cell to give rise to all cells of embryo and subsequently adult tissues; ES CELLS
91
Multipotency
Ability of cell to give rise to different cell types of a given lineage; ADULT STEM CELLS
92
Founder Stem Cell
Fixed number of cells programmed for a specific lineage with a fixed number of divisions; define size of large final structures; TRUE stem cell
93
Transit Amplifying Cell
Transition from cell with stem cell characteristics to a differentiated cell; programmed to divide a limited number of times
94
Asymmetrical division of stem cells
One cell has stem cell characteristics, another cell has the ability to differentiate
95
Independent choice (stem cell maintenance)
Fate of daughter cells as stem cells or terminally differentiated cells is determined stochastically and/or by environment
96
Derivation of embryonic stem cells
From ICM of blastocyst and cultured; capable of indefinite proliferation with unrestricted developmental potential
97
Teratomas
Tumors resulting from proliferation of embryonic stem cells into many different types of tissues (lack of axial or segmental organization)
98
Effect of retinoic acid on ES cells
Induces differentiation into neurons
99
Somatic cell nuclear transfer (SCNT)
Nucleus taken from somatic cell of patient and injected into oocyte of donor (replaces oocyte nucleus); ES cells can be generated from new blastocyst
100
Gene regulatory proteins for ES cells
Oct3/4, Sox2, Myc, Klf4
101
Transcription factors for maintenance of pluripotency in ES cells
Nanog, Oct4, Sox2, FoxD3
102
Adipose derived MSCs
Have ability to self-renew and can be differentiated into many different lineages when manipulated; but can be problematic in real world
103
Bone marrow derived MSCs
Ability to regenerate neuronal-like cells and many others
104
iPS cells
Somatic cells can be reprogrammed to iPS cells by defined, limited sets of transcription factors; cells are "tricked" into becoming pluripotent from multipotent cells - BEST OPTION FOR SC MANIPULATION
105
Anchoring junctions
Cell-cell and cell-matrix adhesions; connected to cytoskeletal elements inside cell
106
Cadherins
Mediate cell-cell connection; connected to ACTIN filaments; homophilic
107
Desmosome
Mediate cell-cell connection; connected to INTERMEDIATE filaments-mechanical strength; homophilic
108
Integrins
Mediate cell-matrix attachment; connected to ACTIN filaments; heterophilic
109
Occluding junctions
Seal gaps between epithelial cells to make an impermeable barrier
110
Channel-forming junctions
Create passageways for small molecules and ions to pass from cell to cell
111
Signal-relaying junctions
Allow signals to be relayed from cell-cell across plasma membranes at cell-cell contact
112
B-catenin role in adhesion and development
Adhesion: intracellular anchor protein on tail of cadherin
Development: signaling molecule that works with Wnt signaling
113
Cortial actin ring
Contraction affects permeability, gastrulation
114
ARVC relation to desmosomes
Missense mutation in Desmocollin-2 is associated
115
Auto-immune, blistering disorders
Due to defects in Desmocollins/desmogleins
116
Tight junction
Forms seal between cells; claudin and occludin proteins form seal - homotypic adhesions
117
Establishing epithelial cell polarity
Full polarization requires separation of apical and basolateral surfaces via tight junction formation; polarity complex controls (Par, Crumbs, Scribble)
118
Gap junctions
Spanned by channel forming proteins including CONNEXINS; pore formed so that SMALL molecules can pass through (up to 1000 MW/glucose)
119
Basal lamina
Separates cells from underlying/surrounding tissue; selective filter, determines cell polarity; usually consists of laminin, collagen, fibronectin
120
Src/FAK complex
Signals downstream of integrins; activates ERK/JNK to regulate cell survival/proliferation/differentiation
121
Glysaminoglycans (GAGs)
Covalently linked to protein in the form of proteoglycans
122
Fibrous proteins
Collagen, fibronectin; structural and adhesive functions
123
Proteoglycans
Hydrated, "ground substance" embeds fibrous proteins; contains repeated GAGs
124
Hyaluronic acid
Repeated disaccharides-glucaronic acid and acetylglucosamine, highly hydrated; ability to withstand compressive forces
125
Collagen
Triple-stranded helical structure rich in proline and glycine; allows stability of helical formation and tight packing
126
Enzymes affecting hydroxylation of collagen
Prolyl and Lysyl hydroxylases
127
Where collagen synthesis occurs
Lumen of ER (of fibroblast)
128
Scurvy
Inability to make collagen - can't hydroxylate proline (defect in prolyl or lysyl hydroxylase)
129
Ehlers Danlos
Defects in prolyl/lysyl hydroxylase causes super flexible skin
130
Elastin
Cross-linked protein via lysyl oxidase; "elastic" - lines up hydrophobic units and decrease of entropy of H2O
131
Marfan's syndrome
Defect in elastin, fibrillin
132
Keratin filaments in epidermis
Attached to DESMOSOMES
133
Olfaction
Olfactory receptor (GPCR) binds to odorant and activates AC, cAMP; action potential relayed to glomeruli in olfactory bulb
134
Actin filaments
Least stable, small, control cell behavior such as shape, locomotion; requires ARP for nucleation
135
ARP
Causes local nucleation of actin filaments; growing filaments drive "push" through cytoplasm; creates polarity
136
Microtubules
Stable; polar (+/- ends); made of tubulin subunits; contain microtubule-organizing center/centrosome
137
Gamma-TuRC
Responsible for nucleation of microtubule growth; nucleated from MTOC
138
Intermediate filaments
Rope-like, large fibers; provide mechanical strength; no nucleotide binding/polarity
139
Endocrine signaling
Long distance signaling; transport to target molecule via blood stream, such as hormones
140
Paracrine signaling
Local signaling affecting nearby cells, such as neurotransmitters
141
Autocrine signaling
Cells respond to their own signals; bind to own receptors, such as growth factor
142
Juxtacrine signaling
Membrane bound signal attaches to target cell, such as immune cells
143
Lipophilic molecules
Lipid soluble molecules that diffuse across plasma membrane and bind to intracellular receptors; ex: steroid hormones
144
Hydrophilic molecules
Require cell-surface receptors to trigger signaling events (water soluble); ex: growth factors
145
GPCR
Seven pass transmembrane protein
146
Heterotrimeric G-proteins
Contain alpha, beta, and gamma subunits; change conformation when bound by a ligand (no catalytic activity)
147
GAP
Inactivates G-protein; accelerates hydrolysis of GTP to GDP (G protein complex comes together)
148
GEF
Changes conformation to release GDP and activate G protein (release alpha subunit with GTP bound)
149
B-arrestin role in GPCR
Shuts off signal relay
150
Adenylate Cyclase
Activated by G-alpha/GTP; activates cAMP; cAMP activates PKA which phoshphorylates other proteins
151
PLC
Activated by G-alpha/GTP; activates DAG and IP3
152
GRK
Phosphorylates GPCR; arrestin binds and prevents conversion of G-alpha/GDP to G-alpha/GTP
153
Gi/o-alpha G proteins
Inhibit AC
154
Gq-alpha G proteins
Activate PLC instead of AC
155
IP3
Release Ca2+ from ER
156
DAG
Activates PKC which phorhphoylates proteins
157
Ras-dependent signaling
Binds Grb2 in signaling process; leads to (slow) alterations in gene transcription
158
Ras-independent singaling
Binds PI3K in signaling process; leads to (fast) alterations in protein/enzymatic activity
159
JAK-STAT Receptors
Most direct rout for impacting transcription; STAT translocates to nucleus
160
Ser/Thr Receptors (Smads)
More direct signaling route; R-Smad/Co-Smad migrate to nucleus
