Biochemistry Flashcards
1
Q
What is the type of cell that makes all types of blood cells?
A
Pluripotent stem cells
2
Q
What are the 3 dereivatives from the pluripotent stem cells?
A
CFU-GEMM (mixed myeloid progenitor cell)
Lymphoid stem cell
NK-precursor
3
Q
What type of cell does the NK-precursor make?
A
Nk-cells lol
4
Q
What are the 2 types of cells that the lymphoid stem cells make?
A
B- and T-lymphocytes
5
Q
What are the 2 eventual cells make from the BFU-E cells fom the CFU-GEMM?
A
RBC’s (using erythrocyte pathway)
Platelets (using megakaryocyte pathway)
6
Q
What are the 3 eventual cells make from the CFU-GMEo pathway?
A
Neutrophils (using CFU-GM)
Monocytes (–> macrophages, using CFU-GM)
Eosinophils (using CFU-Eo)
7
Q
Since RBCs dont have nuclei or mitrochondria, what energy pathway does it use exclusively?
A
Glycolysis
8
Q
Since RBC’s cant make proteins, is depends on what enzyme that determines its lifespan?
A
G6PD
9
Q
What is the intermediate of the glycolysis pathway that is used in the HMP shunt (PPP)?
A
G6P
10
Q
What is the intermediate of the glycolysis pathway that is used in the Rapoport Luberin shunt?
A
1,3-BPG
11
Q
What is the structure of heme?
A
Porphyrin ring with a Fe at its center
12
Q
What are the 2 components in teh first step of heme synthesis?
A
Succinyl CoA + Glycine
13
Q
What is the first enzyme in the heme synthesis pathway to make δ-ALA?
A
δ-ALA synthase
14
Q
What is the last enzyme in the heme synthesis pathway to put a Fe++ molecule in Protoporphyrin IX?
A
Ferrocheletase
15
Q
What is the condition where there is a defect in any enzyme in the heme synthesis?
A
Porphyria
16
Q
Why do vampire and werewolf stories come from people with porphyrias?
A
Cuz the heme intermediates are toxic to the nervous system –> photosensitivity, hallucinations, and seizures
laso, pt have scarring and increased facial hair
17
Q
When hemoglobin is first degredated, what is the product?
A
Heme
18
Q
What is teh like span of a RBC?
A
120 days
19
Q
What is the produce of degredation of heme, which gibes off Fe++ and CO as biproducts?
A
Bilirubin
20
Q
What does bilirubin bind to in the blood once formed?
A
Albumin
21
Q
What molecule binds to bilirubin on the albumin, thus kicking off the albumin and forming bilirubin diglucononide?
A
UDP-glucuronate
22
Q
Where does Bilirubin diglucuronide then put?
A
Bile
23
Q
What is the term for Hb with Fe in the ferric (3+) state?
A
MetHb
24
Q
For congenital MetHbemia, what enzyme is missing, which normally reduces ferric Fe to the ferrous state?
A
Cytochrome B5 reductase
25
What for of Hb can pts also inherit for congential metHbemia?
Hb M
26
Ingestion of what things can cause acquired metHbemia?
Certian oxidants like nitrite, quinones, aniline,a nd sulfonamides
27
What is the treatment for acquried metHbemia?
Administering reducing agents like ascorbic acid or methylene blue
28
What is oxidices by ROS in the RBC so they dont dmg the cell? What pathway keeps this molecule reduced?
Glutathione
PPP/HMPshunt
29
What are the components of the RBC cytoskeleton?
Specrin, actin, bands 4.1 and 4.2
30
Which races are at risk for G6PD deficiencies?
Africans and Mediterraneans
31
What is the inheritance for G6PD deficiencies?
X-linked
32
What medications can cause problems in G6PD deficiencies?
Anti-malarials
33
What 2 cells might u see on blewd smares for G6PD deficiencies?
Bite cells
| Heinz bodies
34
This is a set of disorders common from defect in cytoskeletal proteins, notably ankyrin, spectrin, and Band 3.
Hereditary spherocytosis
35
What happens when RBC's pass through capallaries and the spleen in hereditary sphreocytosis?
they're inflexible (like my time for studying public health) --> change shape to spheres --> hemolysis
36
In blood typing, what Ab's will be present in my blood since I'm type O-?
Ab's to A antigen, B antigen, and Rh antigen
37
What is the universal donor and acceptor?
Donor: O- (like me cuz I'm so giving)
Acceptor: AB+ (like brent cuz hes greedy)
38
What is the suffix to describe the size of RBC's?
-cytic
| micro and macro- are the prefixes
39
What is the suffix to describe the [Hb] in RBC's?
-chromic
40
Iron deficiency, thalassemia mutation, and lead poisoning may lead to impaired synthesis of what molecule?
Hb
41
What is the RBC morphology with impaired hemoglobin synthesis?
Microcytic, hypochromic
42
What 3 things can cause impaired DNA synthesis?
B12 or folic acid deficiency
| Erythroleukemia
43
Impaired DNA synthesis may lead to what RBC morphology?
Macrocytic, normochromic
44
Red cell loss (like from bleeding or hemolysis) may lead to what morphology of RBC's?
NO CHANGE
Normocytic, normochromic
45
Why does B6 deficiency cause the synthesis of heme production to slow?
Hint: molecule
Cuz it requires puridoxal phosphate
46
What is the RBC morphology in B6 deficiency?
Microcytic, hypochromic
pale and small, like a little old lady that isnt getting her B6 vitamins because she was once a student of a geriatrics class and is now showing students the repercussions of elder neglect as she has lost interest in other daily activities over the years and finds that experimental testing keeps her young and happy despite the fact that this experimental testing is deleterious to her health overall.
47
What is the manifestation of pyruvate kinase deficiency?
hemolytic anemia
48
What is the problem if there is inadquate iron intake or excessive loss of iron?
Iron deficiency.
49
What is the problem if there is a squence of codon 6 of the B chain changed from GAG to GTG, which substitutes Val for Glu?
Sicle cell
50
What is the problem if there are mutations in the alpha gene?
alpha thallasemia
51
What is the disorder if there is decreased absorption of B12 or lack of intrinsic factor?
Megalblastic anemia
52
What is the problem if there are deficiencies in the amt or in the structure of alpha or beta spectrin, ankyrin, band 3 or band 4.1?
Hereditary spherocytosis
53
What is the disorder when there are mitations in the PIG-A gene, affecting synthesis of GPI-anchored proteins?
Paroxysmal nocturnal hemoglobinuria
54
How many alpha globin genes are there?
4
55
How many deletions of alpha globin genes do u need to when u start to see microcytic hypochrmic RBC's?
2
56
In addition to severe microcytic hypochromic anemia, what is the other manifestation of 3 alpha globin genes missing?
Splenomegaly
57
Do u die as a hydrops fetalis with 4 missing alpha globin genes?
Um, yes.
58
What is the homotetramer called of excess b chains?
HbH
like HGH. WHERES THE PROTEIN, MA? I TOLD YOU TO GET ME SOME PROTEIN.
59
Which coag pathway requires factors already present in the blood?
Intrinsic pathway
60
What factor does the intrinsic pathway start with?
XII (Hagemann factor)
61
What induces XII to be activated?
A negatively charged surface
62
What must XIIa have the presence of to proteolytically cleave XI?
HMWK
63
What does XI activate?
IX
64
Which factor is activated in the final step of the intrinsic pathway, once VIII is precipitated?
X
65
What disorder is present in a deficiency of factor VIII?
Hemophilia A
66
What factor is deficient in hemophilia B?
IX
67
What activates factor VII to start the extrinsic pathway?
Ca++
68
What helps VII activate factor X?
factor III
69
What are the 4 phases of homeostasis?
1. vasoconstriction of the injured vessel
2. formation of the platelet plug (1o hemostasis)
3. formation of the fibirin mesh (2o hemostasis)
4. dissolution of the clot
70
After endothelial cell injury, what is the molecule that platelets adhere to to start primary hemostasis?
vWF
71
In addition to platelet adhesion, what is vWF's role on factor VIII?
stabilizes it in the circulation
72
After platelets bind to vWF via Gp1b receptors, what happens?
They change shape and degranulate.
73
What are the 2 molecules released from platelts that promote further platelet activation?
ADP and TXA2
74
What is the substance released by platelets that promotes vasoconstriciton?
serotonin
75
What is the substance released by platelets that stimulates repair of damaged tissue?
PDGF
76
For platelet aggregation to occur, what is the molecule that binds inbetween the GpIIa/IIIb receptors of the platelets?
fibrinogen
77
Which factors are vit K dependent for their synthesis?
II, VII, IX, X, C, and S
78
What class of drugs work by inhibiting the regeneration of vitamin K to its active form?
Coumarin anticoagulants
| dicumarol and warfarin
79
The inhibition of COX by ASA cause the inability to synthesize which molecule, which is required for activation and aggregation of platelets?
TXA2
80
What do platelets lack which cause the permanent effects of ASA inhbiting COX?
a nucleus
81
What does ASA also inhibit, which normally opposes platelet aggregation, but typically is regenerated within a few hours?
Prostacyclin
82
What is the molecule that turns plasminogen --> plasmin?
t-PA
83
What does plasmin break apart in blood clots?
fibrin and fibrinogen
84
What is the requirement for t-PA to work on plasminogen?
plasminogen has to be bound to fibrin (trapped in the clot)
85
What is the molecule that binds to free plasmin and inactivates it?
a2-antipalsmin
86
What would be the general problem if you lacked a2-antiplasmin?
Tendency to bleed
| cant inhibit plasmin --> constant breakdown of fibrin and fibirinogen --> no clot formation --> bleeeeeeed
87
What 2 enzymes can bind to free plasminogen and activate it?
Urokinase (54kD enzyme form the kidney)
| Streptokinase (45kD bacterial protein, which activates plasminogen w/o cleavage)
88
What do urokinase and streptokinase not require to activate plasminogen, unlike t-PA?
Fibrin
89
What molecule is on the surface of the endothelail cells that ↓ blood clotting by binding thrombin?
Thrombomodulin
90
What 2 factors do proteins C and S inhibit?
Va and VIIIa
91
What molecule on the endothelial cell surface inhibit ATIII?
heparan sulfate
92
What is the inheritance of hemophilia A?
XR
93
Where does the bleeding occur in hemophilia A?
deep tissues and joints.
94
What is the treatment for hemophilia A?
recombinant FVIII
95
What is the inheritance for hemophilia B?
XR
96
Despite lacking IX (a different factor than hemophilia A), why do hemophilia A and B have basically the same problems?
Cuz both VIII and IX are in the intrinsice pathway and if either arent there then the intrinsic pathway doesnt work
97
So how do u distinguish hemophilia A from B?
protein electrophoresis or DNA analysis
98
What is the inheritance for vW disease?
AD
99
True or False: vW disease is the most common bleeding disorder.
True
100
Where do u bleed in vW disease?
mucous membranes (nose, menorrhegia, eyes)
101
What is the treatment for vW disease?
FFP and platelets
102
This is a disorder of very low platelet levels in the blood (<50,000/ul).
thrombocytopenia
103
What is normal levels of platelets in the blood?
150-300k
104
Where does the bleeding occur in thrombocytopenia?
capillaries and small venules
105
What is the treatment for thrombocytopenia?
whole blood, platelet packs, and splenectomy
106
What are newborns injected with to prevent a deficiency, as their gut flora arent proficient yet?
Vitamin K
107
This is a diffuse, itnravascular activation of the clotting cascade and fibrinolysis, resulting in a consuption of coagulation factors.
DIC
108
What happens to the PTT and PT in DIC?
prolonged
| u use up ur coag factors
109
What are the causes of DIC?
```
Obstetric complication
Sepsis
Adenocarcinoma
Acute promyelocytic leukenia
Rattlesnake bite
```
110
What do u add to a blood sample in a PTT to activate the intrinsic pathway?
koalin clay
111
What do u treat the blood with in a PT to activate the extrinsic pathway?
thromboplastin (tissue factor, which activates VII)
112
This is the test where u mix 50:50 of the pts blood and a standard sample, where lengthened showes a circulating anticoagulant and a normal may correct a deficiency.
Mixing test
113
This is the test where u stab the pt and see how good platelets are at forming the primary plug.
Bleeding time
114
What is the function of the following plamsa proteins?
antichymotrypsin, a1-antitrypsin, a2-macroglobulin, and antithrombin
Antiproteases
115
What is the function of the following plasma proteins?
Various coagulation factors, fibrinogen
blood clotting
116
What is the function of the following plasma proteins?
immunoglobulins, complement proteins, and B2-microglobulin
Immunne defense
117
What is the function of the following plasma proteins?
CRP, a1-acid glycoprotein
Inflammation
118
What is the function of the following plasma proteins?
AFP
oncofetal
119
What is the function of the following plasma proteins?
Albumin, ceruloplasmin (Cu), cotricosteroid-binding globulin (cortisol), Haptoglobin lipoproteins, hemopexin, retinol-binding protein, sex-hormon-binding globulin, thyroid-binding globulin, transferrin and transthyretin
Transport or binding proteins
120
What is the major protein of the human plasma (60%)?
Albumin
121
What is the condition when serum albumin levels fall?
Edema (Kwashiorkor)
122
This is the molecule that binds to free Hb in a tight noncovalent bond and prevents loss of free Hb, and therefore iron, through the kidneys.
Haptoglobulin (Hp)
123
What is the main component of Hp?
a2-globulin fraction
124
In what condition do Hp levels drop?
hemolytic anemia
125
This molecule inhibits serum proteases (esp elastase) and protects against degeneration of alveolar tissue.
a1-antitrypsin
126
What are the clinical manifestations of A1AT deficiency?
go back to respiratory..
Emphysema and cirrhosis (the ZZ form)
127
What is the plasma protein that binds to copper and decreased in Wilson's disease?
Ceruloplasmin
128
Which vitamin promotes iron absorption in the GI?
Vitamin C
129
If Fe isnt stored in Hb and Mb, how is it stored?
Ferritin and Hemosiderin
130
This is the condition where there is an iron overload in the tissues.
hemosiderosis
131
Is there usually a high or low amount of fettirin in the tissues?
low
132
This is a B1-globulin synthsized in the liver that transports Fe through the blood.
Transferrin
133
How many ferric ions can tranferrin carry?
2
134
What is the test to see the transferrin concentration?
TIBC
135
What are pre-menopausal women prone to because of menses?
Iron deficiency anemia
136
What are the RBC characteristics of iron deficiency anemia?
hypochromatic microcytic anemia
137
What are the pt Sx of iron deficiency anemia?
fatigue, pallor, and reduced exercise capacity
138
What cells are increased in iron deficiency anemia, which reflexts the imapired ferrochelatase-catalyzed incorportation of iron into the protoporphyrin IX ring?
Red-cell protoporphyrin
139
What is the most common inherited metabolic disorder in the white population, which is characterized by excessive storage of iron in tissues?
Hemochromatosis
140
In primary hemochromatosis, what gene is mutated, which the normal product is a glycoprotein that binds transferrin receptor?
HFE gene
141
What is the typical etiology for secondary hemochromatosis?
multiple blood transfusions
142
This is an X-linked diorders that is fatal in infance, where there is a decrease in activity of copper-dependent enzymes?
Menkes disease
143
What is the mutation in Menkes disease?
extra-hepatic Cu++-binding ATPase
144
This is an AR condition where there is defective excretion of Cu2+ into bile and consequent accumulation of Cu in liver, brain, and other organs.
Wilsons disease
145
Levels of what protein is decreased on labs in Wilsons?
Ceruloplasmin
146
What is the treatment for Wilsons disease?
Penicillamine
147
CRP, A1AT, Hp, alpha1-acid hlycoprotein, and fibrinogen are all markers of what?
Acute phase proteins for inflammatory states.
