book- hematopoietic system Flashcards
(92 cards)
1
Q
blood pH and volume
A
slightly alkaline, pH of 7.4
WBC, RBC and platelets
5 litres
2
Q
where is blood formed in utero vs after birth
A
in utero: bone marrow, liver, spleen, lymphoid tissue
after birth: exclusively in bone marrow
kids: long bones (femur, tibia etc.)
adults: pelvis, cranium, vertebrae, sacrum
3
Q
erythrocyte (RBC) structure and function
A
bicaoncave, contain hemoglobin bound to heme, lifespan of 120 days
O2 and CO2 trasnport
4
Q
leukocytes (WBC) 2 main types and subtypes
A
granulocytes
- neutrophils
- eosinophils
- basophils
- mast cells
agranulocytes
- lymphocytes (T and B cells)
- monocytes (macrophages)
5
Q
majority of WBCs ~60% are
A
neutrophils
6
Q
neutrophil function
A
bacterial infection, acute inflammation
7
Q
lymphocyte function
A
adaptive immunity; B cells (antibodies) and T cells (cell mediated)
8
Q
monocyte function
A
become macrophages in tissue for phagocytosis and antigen presentation
9
Q
eosinophils function
A
parasites, allergic rxn, asthma
10
Q
basophil function
A
histamine release and allergic rxn
11
Q
say which leukocytes (WBC) for each of the following categories
bacterial defense
viral defense
parasitic infection
allergic rxn
antibody production
chronic inflammation
A
bacterial defense: neutrophils, monocytes/ macrophages
viral defense: lymphocytes (esp T cells)
parasitic infection: eosinophils
allergic rxn: basophils, eosinophils
antibody production: B cells –> plasma cells
chronic inflammation: macrophages, lymphocytes (B and T cells)
12
Q
what do the granules in basophils contain
A
histamine
13
Q
types of T cells
A
CD4+ helper cells secrete cytokines to modulate immunologic processes
CD8+ suppressors or killers
NK natural killer cells are specialized T helper cell-indecent lymphocytes
14
Q
NK cells
A
type of specialized T helper cell in innate immunity; a rapid and non specific defense against viruses and tumors
15
Q
what do platelets come from a where
A
megarkaryocytes in the bone marrow
lifespan <14 days
plug to block bleeding
16
Q
factors to get pluripotent stem cell into lymphoid vs myeloid progenitors
A
lymphoid (B and T cell): Il7
myeloid: TPO (thrombopoietin)
17
Q
factors to get lymphoid progenitor into T or B cell
A
both: IL7
B cell: IL6
18
Q
how to get myeloid progenitor into megakaryocte/ erythroid progenitor
A
EPO (erythropoietin)
eventually make platelets and RBCs
19
Q
factor to get granulocyte/ macrophage progenitor into granulocyte vs monocyte
A
granulocyte (neutrophil, basophil, eosinophil) via G-CSF
get into eosinophil via IL5
get into basophil via IL3
monocyte via M-CSF
20
Q
hemoglobin
A
iron-containing protein in red blood cells (RBCs) that transports oxygen (O₂) from the lungs to tissues and carbon dioxide (CO₂) back to the lungs.
2 Alpha and 2 beta chains in adult HbA
4 heme groups: 1 Fe2+ bound to O2 each
21
Q
myoglobin
A
oxygen-binding protein found primarily in cardiac and skeletal muscle, where it serves as an oxygen reservoir and transporter within muscle tissue.
store O2 in muscle
22
Q
bohr effect
A
↓ pH or ↑ CO₂ → ↓ O₂ affinity → O₂ release to tissues from hemoglobin
The Bohr effect describes how changes in blood pH and CO₂ levels affect hemoglobin’s oxygen affinity, facilitating oxygen delivery to tissues that need it most.
Active tissues produce more CO₂ and H⁺ → Bohr effect enhances O₂ unloading exactly where it’s needed.
In lungs, lower CO₂ and higher pH increase O₂ affinity → facilitates O₂ loading onto Hb.
23
Q
things that shift the oxygen hemoglobin curve right which decreases its affinity for oxygen and has better offloading
left shift= increase O2 affinity and have it hold onto O2 more tightly
A
“CADET, face Right!”
CO₂, Acid (low pH), DPG (2,3-BPG), Exercise (↑ temp), Temperature
for example anemia, high altitude, smoking, COPD so that more o2 can be delivered to tissue
24
Q
how hemoglobin acts as a pH buffer
A
bind 2 Hydrogen ions to every 4 oxygen molecules
CO2 can also be carried by Hb to the lungs
25
where does heme synthesis occur
bone marrow and liver
26
key regulatory enzyme in heme synthesis and for which step
delta-aminolevulinate synthase (ALA synthase); first step in mitochondria where it combines glycine with succinyl-CoA (and needs B6; pyridoxal phosphate to do so) to get delta-aminolevulinic acid (ALA)
27
inhibitors of heme synthesis
Lead inhibits:
ALA dehydratase
Ferrochelatase
“Lead blocks the First and Last”
(ALA dehydratase = 1st cytosolic enzyme, Ferrochelatase = final mitochondrial enzyme)
28
steps of heme synthesis
🔢 Steps of Heme Synthesis
1. Glycine + Succinyl-CoA → δ-Aminolevulinic Acid (ALA)
* Enzyme: ALA synthase (rate-limiting step)
* Location: Mitochondria
* Requires Vitamin B6 (pyridoxal phosphate)
* Regulated by negative feedback from heme
2. 2 ALA molecules → Porphobilinogen (PBG)
* Enzyme: ALA dehydratase
* Location: Cytosol
* Inhibited by lead
3. 4 PBG molecules → Hydroxymethylbilane
* Enzyme: PBG deaminase (also called HMB synthase)
* Location: Cytosol
* Deficiency causes Acute Intermittent Porphyria
4. Hydroxymethylbilane → Uroporphyrinogen III
* Enzyme: Uroporphyrinogen III synthase
* Location: Cytosol
5. Uroporphyrinogen III → Coproporphyrinogen III
* Enzyme: Uroporphyrinogen decarboxylase
* Location: Cytosol
* Deficiency causes Porphyria Cutanea Tarda
6. Coproporphyrinogen III → Protoporphyrinogen IX
* Enzyme: Coproporphyrinogen oxidase
* Location: Mitochondria
7. Protoporphyrinogen IX → Protoporphyrin IX
* Enzyme: Protoporphyrinogen oxidase
* Location: Mitochondria
8. Protoporphyrin IX + Fe²⁺ → Heme
* Enzyme: Ferrochelatase
* Location: Mitochondria
* Inhibited by lead
29
hemostasis
1st stage of wound healing involving platelet, vessel and coagulation factors to stop bleeding
30
three phases of hemostasis
1. vascular spasm
- blood vessels vasoconstrict
2. platelet plug formation
- endothelial injury exposes collagen in vessel wall
-platelets adhere to collagen via von willebrand factor (vWF)
-adhesion triggers degranulation; release ADP and serotonin to activate platelets
-platelets aggregate via thromboxane A2
3. coagulation
-convert fibrinogen to fibrin
31
what factors cause platelet activation and aggregation for hemostasis
activate: ADP and serotonin
aggregate: thromboxane A2
32
what activates the extrinsic vs intrinsic coagulation cascade
extrinsic: damage to tissue cells cause release of tissue factor
intrinsic: vessel endothelium ruptures and exposes underlying tissues (contact activation)
33
vitamin K is required for the synthesis of which coagulation factors made by the liver
factors II, VII, IX, X
2,7,9,10
34
what do the intrinsic and extrinsic pathway both form and what does it do
prothrombin activator; turn prothrombin into thrombin
thrombin then catalyzes the reaction of fibrinogen into fibrin monomers that form a mesh
35
heparin
what is its structure
where is it stored
function
what it binds
~anticoagulant~
sulfated glycosaminoglycan
stored in mast cells and basophils; released at sites of injury
doesnt lyse existing clots, but prevents new ones from forming
binds antithrombin; inhibiting thrombin and clotting factor Xa
36
heparin
Heparin is a naturally occurring anticoagulant that enhances the activity of antithrombin III to inhibit clotting factors, mainly thrombin (factor IIa) and factor Xa.
37
factors in extrinsic and intrinsic pathway
intrinsic: 12, 11, 9, 8
extrinsic: 3, 7
common: 10, 5, 2, 1
Intrinsic: "If you’re INside, you need 12, 11, 9, and 8"
Extrinsic: "You get hurt OUTside → use tissue factor (III) + 7"
Common Pathway: "1×2×5 = 10" → I, II, V, X
38
what removes old RBC from circulation
phagocytic action of macrophages
39
hepcidin
Liver hormone that inhibits iron release from enterocytes and macrophages → ↓ iron absorption and recycling
40
hemosiderin
Iron storage in conditions of iron overload
41
ferritin
Major storage protein for iron
42
transferrin
Transports Fe³⁺ in blood
43
Key Molecules in Iron Homeostasis
-transferrin
-ferritin
-hemosiderin
-hepcidin
Transferrin: Transports Fe³⁺ in blood
Ferritin: Major storage protein for iron
Hemosiderin: Iron storage in conditions of iron overload
Hepcidin: Liver hormone that inhibits iron release from enterocytes and macrophages → ↓ iron absorption and recycling
44
heme degradation steps and location
in spleen, liver, bone marrow
split hemoglobin into globin and heme
globin (protein) gets degraded into amino acids
heme is converted into biliverdin and CO2 and then into bilirubin
bilirubin is water soluble, so complexes with albumin in blood stream. once in the liver, bound bilirubin reacts with glucuronic acid to form conjugated bilirubin
most conjugated bilirubin is secreted into small intestine with bile
enterohepatic recirculation of bilirubin: gut flora can deconjugate bilirubin into urobilogens which get reabsorbed in colon and oxidized back into bilirubin by hepatocytes
45
enterohepatic recirculation of bilirubin (after heme degradation)
enterohepatic recirculation of bilirubin: gut flora can deconjugate bilirubin into urobilogens which get reabsorbed in colon and oxidized back into bilirubin by hepatocytes
46
iron degradation
removed from heme molecules by macrophages, transfer ferric (Fe3+) form of iron to transferrin molecules that are exported to the blood as transferrin-iron complexes
47
major storage site for iron
whats it bound to
liver
when stored intracellular its bound to ferritin (iron-free ferritin is called apo-ferritin)
liver also makes transferring, major transport protein for iron in the blood
48
iron excretion
no true mechanism for excretion
49
main site of iron utilization is
bone marrow (for erythropoiesis- RBC production)
50
what increases iron absorption and how
vitamin C via chelation
51
heme iron-containing molecules
hemoglobin, myoglobin, cytochrome p450 enzymes, peroxidases, cytochrome, catalase
52
non-heme iron containing molecules
xanthine oxidase (purine catabolism), ribonucleotide reductase (DNA synthesis), 5' deiodinase (T4 --> T3)
53
lactoferrin role
chelates iron during infections or chronic inflammation to prevent its use by microbes and prevent exacerbation of inflammation
can lead to anemia of chronic disease if chronic
54
co factor for ALA synthase, the rate limiting enzyme in heme synthesis
vitamin B6
1st step where glycine and succinyl coa are combined to make delta aminolevulinic acid (ALA)
55
anemia
any condition that causes total number of RBCs, amount of hemoglobin, or volume of packed RBCs to decrease
56
anemia causes what to oxygen
hypoxia; low O2
57
sx of anemia
dyspnea on exertion, fatigue, lightheaded or dizzy, tinnitus, headache
long term: pallor, tachycardia, systolic ejection murmur, orthostatic hypotension
58
iron deficiency anemia
from chronic blood loss, increased need for O2 and blood, deficient intake, poor absorption
chronic fatigue, pale mucous membranes,
low RBC, low hemoglobin, low hematocrit, small RBCs (low MCV, MCH, MCHC), low serum iron, low serum ferritin
59
macrocytic anemia
examples, why big?? sx, labs
vitamin B12 or folic acid deficiency or malabsorption (pernicious anemia)
leads to inability to complete DNA synthesis --> RNA proliferation continues and results in cellular expansion (enlarged erythrocytes)
sx: fatigue, lethargy, glossitis, weight loss, peripheral neuropathy, depression, paranoia
labs: low RBC, low hemoglobin, low hematocrit, large cells (increased MCV, MCH, MCHC), low serum B12, low serum folate, low serum or urine methylmalonic acid, high serum homocysteine, polysegmented neutrophils
60
microcytic vs macrocytic vs normocytic anemia
microcytic: small RBCs (low MCV), not enough hemoglobin (heme or globin) (i.e. iron deficiency, thalassemia, chronic disease)
normocytic: normal RBC size but fewer RBCs or early destruction (i.e. blood loss, hemolysis, aplastic anemia)
macrocytic: large RBCs; DNA synthesis issue (i.e. vitamin B12 or folate deficiency)
"Small cells = Iron problems (Microcytic)"
"Normal cells = Less RBCs or they die early (Normocytic)"
"Big cells = DNA problems (Macrocytic)"
61
pernicious anemia
autoimmune; reduce absorption of food bound B12 by destroying intrinsic factor
parietal cells in stomach are destroyed by antiparietal antibodies
also damages chief cells, leading to achlorhydria and lack of pepsinogen secretion
sx: chronic dyspepsia, B12 deficiency sx
62
pernicious anemia
An autoimmune disorder causing vitamin B12 deficiency due to loss of intrinsic factor (IF).
63
aplastic anemia
A bone marrow failure syndrome causing pancytopenia (low red cells, white cells, and platelets) due to failure of hematopoietic stem cells.
64
aplastic anemia
bone marrow failure; loss of RBC precursors
from radiation, drugs, viral infection, idiopathic
bone marrow is hypo cellular; all cell lines are decreased (RBCs, WBCs, platelets)
sx: pallor, fatigue, dyspnea, headache, palpitations, bleeding gums, mouth ulcers
65
primary vs secondary polycythemia
and main effects
Primary: intrinsic bone marrow problem (low EPO)
Secondary: high EPO from hypoxia or tumors
symptoms mainly due to increased blood viscosity and volume --> hypertension, headache, pruritic, bleeding (paradoxical), splenomegaly, visual disturbances
66
polycythemia
higher than normal RBCs (asses via hematocrit levels)
primary: polycythemia's veracity, polycythemia's rubra vera, erythremia)
secondary: altitude related etc.
67
polycythemia vera (primary)
myeloproliferative disorder; neoplastic clonal proliferation of myeloid stem cells in marrow --> increased RBCs (also moderate increase in circualting platelets and granulocytes)
sx: vertigo, headache, pruritic, dizziness, tinnitus, angina, intermittent claudication, rarely bleeding complictions
68
secondary polycythemia
secondary to increases in production of erythropoietin or conditions that cause increased RBCs (i.e. high altitude, right to left shunts, shock, abnormal hemoglobin, blockage at blood air barrier)
sx: cyanosis, headache, lethargy, confusion, ruddy complexion
69
which coagulation factors are deficient in hemophilia A, B and C
A = VIII
B= IX
C= XI
70
hemolysis in hemolytic anemia
destroy RBC from mechanical trauma, complement induced damage, extravascular hemolysis
sx: jaundice, hemosiderosis (systemic deposition of iron), anemia sx
71
sickle cell anemia
genetic; abnormal hemoglobin
heterozygous
deformed RBCs in circumstances of low O2 tension --> obstruct capillaries --> removed and destroyed by spleen
sx: hemolytic anemia, chronic leg ulcers, infarcts to lungs and spleen, aplastic crises
72
thalassemias
whats deficient? what type of anemia does it cause?
deficient production of either of the two globin chains of hemoglobin
causes hypochromic and microcytic anemia
73
hereditary spherocytosis
familial hemolytic disorder; intrinsic defects in RBC membrane proteins that results in loss of erythrocyte surface area
round RBCs (microspherocytes) that are rapidly destroyed by spleen
sx: mild pallor, intermittent jaundice, splenomegaly
74
glucose 6 phosphate dehydrogenase deficiency
x linked disorder; causes hemolytic anemia during oxidative stress
-------
Pathophysiology:
G6PD is crucial for the pentose phosphate pathway, generating NADPH.
NADPH keeps glutathione reduced, protecting RBCs from oxidative damage.
Without enough G6PD → RBCs are vulnerable to oxidative stress → hemolysis.
75
hemophilia
blood coagulation disorders from absence or impaired activity of clotting factors --> prolonged bleeding
most males because its X linked recessive
76
von willebrands disease
platelets need vWF to adhere to endothelial basement membrane and begin a clot and it also stabilized factor VIII
without it --> increased bleeding time
77
vitamin K deficiency impacts on blood
impacts blood clotting; needed for synthesis of factor II (prothrombin), VII, IX, X
78
thrombocytopenia
reduction in number of platelets --> abnormal bleeding
decreased production, sequestration or increased destruction of platelets
bone marrow damage, splenomegaly, congenital, DIC
79
which type of leukemia happens in kids
ALL; acute lymphoblastic or lymphocytic leukemia
80
leukemia
A group of malignant disorders involving proliferation of abnormal white blood cells in bone marrow and blood.
Common Symptoms
Fatigue, pallor (anemia)
Frequent infections (neutropenia or dysfunctional WBCs)
Easy bruising or bleeding (thrombocytopenia)
Lymphadenopathy, splenomegaly (especially in CLL and CML)
Bone pain (especially in acute leukemias)
81
Chronic Myeloid Leukemia (CML) findings
Philadelphia chromosome (BCR-ABL fusion); splenomegaly; fatigue
82
Acute Myeloid Leukemia (AML) findings
Fatigue, infections, bleeding; Auer rods in blasts on smear
83
Chronic Lymphocytic Leukemia (CLL) findings
Often asymptomatic; lymphadenopathy; smudge cells on smear
84
disseminated intravascular coagulation (DIC)
A serious condition characterized by widespread activation of the coagulation cascade, leading to formation of microthrombi throughout the bloodstream, followed by consumption of clotting factors and platelets causing bleeding.
Triggered by massive tissue injury, infection, or other severe insults →
Excessive thrombin generation → widespread fibrin clots in small vessels →
Consumption of platelets and clotting factors (“consumption coagulopathy”) → bleeding risk
Activation of fibrinolysis → breakdown of clots → bleeding worsens
85
disseminated intravascular coagulation (DIC)
hemorrhagic syndrome; following the uncontrolled activation of clotting factors and fibrinolytic enzymes
usually triggered by massive tissue damage, sepsis, or pregnancy
acute DIC: clotting then fibrin deposition and consumption of clotting factors. fibrinolytic and anticoagulation systems try to break down clots but are overwhelmed. fibrin degradation products (d-dimers) inhibit fibrin polymerization and block platelet function
86
leukemias
AML
ALL
CML
CLL
which is most common
WBC disorder; either myeloid or lymphoid precursors
AML: from prior chemo
--> fatigue, anemia, SOB, bruise, frequent infections
ALL: idiopathic, chemicals, ionization, in kids 2-5yrs. chromosomal translocations
--> fatigue, anemia, bruise, lymphadenopathy, frequent infections
CML: Philadelphia chromosomal translocation on chromosomes 9 and 22
--> lasymptomatic or frequent infections, anemia, bruising, splenomegaly
CLL: most common leukemia; affects B lymphocytes
--> lymphocytosis, anemia, splenomegaly
87
multiple myeloma
neoplasm of plasma cell (B cells that are activated to make antibodies)
sx: bone pain, fractures, hypercalcemia, bacterial infections, renal failure
88
lymphomas
neoplasms of lymphoid cells;
Hodgkins vs non-hodgkins
89
key features of Hodgkins vs non-hodgkins lymphomas
Hodgkins: B cells; reed-stern berg cells, pink nucleolus cant make antibodies, loss of IkB inhibitor on NFKB inflammatory mediator. associated with EBV infection
--> painless lymphadenopathy, spleen or liver enlarged, pel-ebstein fever
Non-Hodgkins: B cell or T cell lymphoma. associated with EBV and HTLV-1 infection. especially in elders, ionizing radiation, autoimmune, chemicals, h.pylori.
--> lymphadenopathy, anemia, fatigue, weight loss, CNS or GI lymphomas possible
90
babesiosis
organism, vector, sx
babes micro from ixodid ticks; infects RBCs
sx: hemolytic anemia, mild fever/flu
91
malaria
organism, life cycle , risks, sx, dx
plasmodium falciparum, p. malariae, p. ovale, p. vivas
vector: anopheles mosquito
mosquito injects sporozoites which asymptomatically infect hepatocytes --> they asexually divide to form merozoites in hepatocytes (liver cycle)
then after 1 wk invade RBCs and destroy them and consume hemoglobin (erythrocytic cycle)
sexual cycle: some merozoites mature into male and female gametocytes
risks: endemic area, poverty
sx: jaundice, splenomegaly, hepatomegaly, anemia, fever, polyuria, rapid pulse, headache, nausea
malarial paroxysms occur every few days (Periodic episodes of fever, chills, and sweating caused by synchronized rupture of infected red blood cells releasing merozoites and toxins.)
dx: IgM antibodies in initial infection then later IgG response
92
schistosomiasis
schistosoma spp.
impacts the GI or GU tracts; have snail as intermediate host
urinary bladder, bowel and liver dysfunction
worms go into mesenteric veins or UB veins. eggs induce granuloma formation and fibrosis
------------
A parasitic infection caused by blood flukes (Schistosoma species).
Cercariae released by freshwater snails penetrate human skin → migrate to blood vessels → mature into adult worms → lay eggs → eggs cause inflammation and fibrosis.
