Hematology Flashcards
1
Q
consider a situation after onset of obstruction in the lymph vessel
a. capillary pressure decreases
b. capillary pressure increases
c. capillary pressure remains unchanged
d. this leads to increased interstitial colloid pressure
A
capillary pressure remains unchanged - related to heart function or blood pressure NOT lymph
and colloid pressure is a function of movement across membrane (affected by proteins)
2
Q
how does histamine affect colloid pressure?
A
histamine allows the movement of proteins across membrane, thereby increasing colloid pressure
3
Q
how much of total body weight is water?
A
~70% (~40 L in a 70 kg man)
4
Q
what does body water volume change with?
A
age, sex, body fat (obesity)
5
Q
blood volume of water in women vs men
A
5 L in women and 5.5 L in men
6
Q
under normal conditions, average intake of water is
A
~2.3 L/day
7
Q
prolonged heavy exercise changes output of water by increasing/decreasing water output in
A
increasing lungs (breathing), sweat (~50x)
decreasing urine
higher total output
8
Q
2 main fluid compartments and volume in each
A
intracellular (~28 L) and extracellular (~14 L)
9
Q
what is intracellular fluid?
A
fluid occupying the space within the cells (i.e., cytoplasm)
10
Q
what is extracellular fluid?
A
interstitial fluid (~11L), plasma (~3 L), and small compartments such as cerebrospinal fluid, intraocular fluid and fluids of the GI tract
11
Q
interstitial fluid has the same constituents as plasma except
A
large proteins (present at low concentrations in plasma and even smaller concentrations in interstitial fluid)
12
Q
relative permeability
A
size determines movement and movement determined by osmotic pressure
13
Q
what is the relationship between molecule size and permeability
A
inverse relationship
14
Q
average size of pores
A
~6-7 nM
larger in liver (liver is leaky) and smaller in brain
15
Q
colloid osmotic pressure is also known as
A
oncotic pressure
16
Q
colloid osmotic pressure is caused by
A
the presence of proteins
17
Q
osmotic pressure increases when
A
protein concentration increases
this affects the movement of water and volume (i.e., more water creates higher volume) by drawing water to where there is a higher protein concentration
18
Q
3 major types of proteins in the plasma in order of abundance
A
albumin, globulin, fibrinogen
19
Q
total oncotic pressure under normal conditions
A
28 mmHg
20
Q
albumin’s contribution to oncotic pressure
A
21.8 mmHg (most abundant)
21
Q
fibrinogen’s contribution to oncotic pressure
A
0.2 mmHg (least abundant)
22
Q
globulin’s contribution to oncotic pressure
A
6.0 mmHg (second most abundant)
23
Q
albumin
A
most abundant plasma protein and nonspecific carrier protein - increases half-life when bound
24
Q
globulin
A
proteins with specificity: e.g., specific carrier proteins, enzymes, immunoglobulins
25
fibrinogen
key factor in blood clotting: polymerizes into long fibrin threads during coagulation
26
fluid movement in/out capillary is affected by
starling forces (hydrostatic pressure + oncotic pressure)
27
outward pressure on capillaries is determined by
capillary pressure = PUSH (blood pressure) + interstitial fluid colloid osmotic pressure = PULL (small amounts of proteins in interstitial fluid)
28
inward pressure on capillaries is determined by
plasma colloid osmotic pressure = PULL (high protein concentration in plasma) + interstitial fluid pressure = PUSH
29
net force between capillary and interstitial compartment
outward force = 28.3 mmHg
inward force = 28.0 mmHg
NET OUTWARD FORCE toward interstitial compartment = 0.3 mmHg - sufficient for small movement from plasma to interstitial fluid
30
interstitial compartment contains
collagen fibres, proteoglycan filaments, interstitial fluid (tissue gel), and free flowing water (~1%)
31
proteoglycan filaments are made up of
98% hyaluronic acid (traps water) and 2% protein
99% of interstitial fluid is entrapped among the proteoglycan filaments, resulting in tissue gel
32
movement of solutes in the interstitial compartment is by
molecular diffusion through the gel (95-99% as fast as in fluid)
33
conditions that increase fluid in interstitial compartment result in
edema (increase the small pocket of free fluid) = swelling due to accumulation of excessive fluid that may result from changes in osmotic colloid pressure
34
presence of proteoglycan, gel formation and collagen support ensures
uniform distribution of fluid within body regardless of body position/gravity, maintenance of optical intracellular distance allowing uniform diffusion of dissolve gases and solutes, mechanical support (giving shape to body parts)
35
for the lymphatic system, the 0.3 mmHg difference in outward pressure from the capillaries causes
fluid movement from capillaries into lymph
36
is solute concentration higher in arterial or venous blood system?
arterial
37
what does the lymph system use to prevent back flow?
1 way valves
38
lymph system
an accessory route for transport of fluid and macromolecules from interstitial space to veins
39
what do lymph nodes contain and what is their function?
contain phagocytic cells and filter lymph to remove foreign blood contaminants before drainage into veins
40
lymph flow is a function of
interstitial fluid pressure
41
elephantiasis is caused by threadlike filarial worms and leads to lymphedema + necrosis by
blockage of lymphatic flow which increases pressure in interstitial compartment, changing starling forces and blood flow
42
necrosis
tissue death - often requires amputation
43
volume of cerebrospinal fluid
150 mL; provides cushioning support for brain
44
pressure of intraocular fluid
15 mmHg; maintains sufficient pressure in eyeball to keep it distended - tightly regulated to prevent glaucoma or blindness
45
volume of fluid compartment of the GI tract
potential space = 15 mL under normal conditions
46
volume of fluid compartment (pleural cavity) of the lung
mucoid fluid = 10 mL - provides lubrication for easy movement of lung
47
some examples of small fluid compartments
pericardial cavity (heart), peritoneal cavity (intestine, stomach, liver), joint spaces, bone and cartilage
48
haemopoiesis
production of blood cells
49
all blood cells originate from the process of
differentiation of pluripotential hemopoietic stem cells
50
pluripotent stem cells first differentiate into either
lymphoid or myeloid stem cells
51
lymphoid stem cells differentiate into
NK cells, B lymphocytes or T lymphocytes
52
myeloid stem cells differentiate into
basophils, eosinophils, neutrophils, monocytes, platelets, erythrocytes (RBC)
53
once cell is committed, is this process reversible or irreversible?
irreversible
54
what factor controls proliferation and differentiation of blood cells?
differentiation factors like cytokines
55
after stimulation by differentiation factors, the cells are now called
committed progenitor cells - destined to become a specific group of blood cells
56
what 2 things increases production of all haemopoietic stem cells?
interleukins and stem cell factors (these are NOT differentiation factors)
57
examples of specific differentiation factors
erythropoietin, thrombopoietin and granulocytes-monocytes colony-stimulating factors
58
erythropoietin
stimulate differentiation to erythrocytes
59
thrombopoietin
stimulate differentiation to megakaryocytes/platelets
60
granulocytes-monocytes colony-stimulating factors
stimulate differentiation to granulocytes and monocytes
61
mature RBC has no
nucleus (anucleated)
62
shape of RBC
biconcave disk - has deformable membrane
~8 microns diameter and ~1-2 microns in thickness (very narrow)
63
why are RBC so narrow?
so they can change shape and pass through small capillaries (soft and squishy to squeeze through narrow cappilaries)
64
RBC constitutes how much of blood volume?
48% in males and 42% in females
65
Hematocrit
Measure of the proportion of volume that is occupied by red blood cells - determined by centrifugation
66
In severe anemia, hematocrit may decrease to
10% (rather than 40-50%) - may result in death
67
Composition of centrifuged blood (parts)
Plasma (water, proteins, nutrients, hormones, etc.), Buffy coat (white blood cells, platelets), hematocrit (red blood cells)
68
Anemia vs polycythemia
Anemia = depressed hematocrit %
Polycythemia = elevated hematocrit %
69
main functions of erythrocytes
- transport of hemoglobin
- hemoglobin also acts as an important acid-base buffer for the blood
- RBC contains carbonic anhydrase which catalyzes production of bicarbonate (important mechanism of CO2 transport)
70
most important oxygen carrier molecule
hemoglobin
71
CO2 and water reaction
which is catalyzed by?
CO2 + H2O > H2CO3 > HCO- + H+
carbonic anhydrase
72
after birth, RBC are produced by
from PHSC in bone marrow but the number of stem cells declines with age
73
relative rates of RBC production in bone marrow in different bones across age
RBC produced in all bone marrow at young age
stop producing from tibia and femur by 20-30 and steady decline in vertebra, sternum, and rib
74
committed cells that become erythrocytes (RBC) are called
colony forming unit erythrocyte (CFU-E)
75
production of erythrocytes (basic steps)
myeloid stem cells (PHSC)
proerythroblast
basophil erythroblast
polychromatophil erythroblast
orthochromatic erythroblast
reticulocyte
mature erythrocyte
76
hemoglobin (Hb)
an iron containing molecule (heme) synthesized in erythroblasts
77
hemoglobin subunit is made up of
a heme group (4 pyrroles + iron) and a globin (peptide)
78
functional Hb consists of how many Hb subunits (heme + globin)?
4 subunits
79
production of hemoglobin
succinyl-CoA > pyrrole (repeat for 4 pyrroles)
4 pyrroles > protoporphyrin
protoporphyrin + iron > heme
heme + globin > Hb subunit (4 subunits required for 1 Hb)
80
globin
peptide - either alpha, beta, gamma or delta
81
most common form of Hb in adult human
Hb A (2 alpha + 2 beta)
82
fetal Hb (Hb F)
2 alpha + 2 gamma
has greater affinity for O2 and can carry 20-30% more O2; concentration is 50% greater than adult Hb (outcompetes it)
83
each Hb molecule can carry how many O2 molecules?
each iron atom can bind to 1 O2 so each Hb molecule (4 iron atoms) can carry 4 O2 molecules
84
the Fe2+ and O2 bond in Hb is
easily reversible (loosely bound)
85
what happens when O2 is bound/unbound to Hb?
conformation change when bound/unbound
bound = OXY
when O2 comes off = DEOXY
86
what happens to the conformation of the RBC when O2 comes off in sickle cell anemia?
globin crystallizes and forms rigid structure - no longer squishy + causes bursts + leads to anemia (lack of RBC)
87
molecular basis of sickle-cell anemia - difference in the codon for Hb changes
amino acid in position 6 from glutamine to valine
88
the specific differentiation factor for RBCs
erythropoietin
89
why does kidney removal usually lead to anemia?
erythropoietin (differentiation factor for RBC) is a glycoprotein produced mainly in the kidney
90
how does low O2 level affect RBC production?
hypoxia stimulates production of erythropoietin which stimulates production of proerythroblasts and RBC
body adapts to low O2 levels by increasing RBC production
91
impaired tissue oxygenation can be caused by
low blood volume, anemia, low Hb, impaired blood flow, pulmonary disease, or high altitude
92
what does lack of vitamin B12 or folic acid (B9) lead to?
reduced DNA synthesis and failure of nuclear maturation which impairs the formation of RBCs
cells cannot progress from the G2 growth phase to mitosis and enlarge in size causing megaloblastic/pernicious anemia
93
what causes megaloblastic anemia (cells gain size but don't divide)?
impaired absorption of vitamin B12
94
total body content of iron
~4 g
65% in the form of hemoglobin and 15-30% stored as ferritin (protein) in liver
95
iron binds to a plasma protein known as
transferrin (beta globulin) and forms transferrin-iron complex
96
transferrin-iron complex binds to _____ and does what?
receptors on the erythroblasts in the bone marrow and increases the delivery of iron to mitochondria to synthesize heme molecules for hemoglobin synthesis
97
abnormalities in transferrin result in
anemia
98
transferrin acts as a control factor of iron absorption from intestine because
saturability of transferrin in the blood limits the absorption of iron from GI tract
transferrin > bile > gut > increased iron transport
therefore transferrin increases absorption of iron into circulation
99
average lifetime of RBC
~120 days (4 months)
100
if RBC doesn't have nucleus/organelles, how does RBC form ATP and other compounds?
has cellular enzymes capable of limited metabolism to form ATP and other compounds
101
how do RBCs rupture/deteriorate over time?
metabolic capability progressively worsens with time resulting in membrane weakening and rupture of RBC particularly in tight spots of the spleen
102
how are damaged RBCs removed?
mainly phagocytosed
starts leaking compounds recognized by macrophages (trigger for removal)
103
what happens to iron when damaged RBCs are removed?
released iron binds to transferrin for synthesis of new hemoglobin or binds with ferritin for storage
104
what happens to porphyrin (4 pyrroles) in Hb when damaged RBCs are removed?
porphyrin is converted to bilirubin which is conjugated and released into blood and bile
105
platelets
small fragments of cells shaped like oval discs of 2-4 microns in diameter, derived in the bone marrow from large megakaryocytes
half life = 8-12 days (short)
106
megakaryocytes
giant cells with multiple copies of DNA in the nucleus
edges break off to form cell fragments (platelets)
107
platelets contain
surface glycoprotein (surface receptors) that recognize tissue matrix protein (i.e., collagen) and damaged endothelial cells
108
platelets do not have a
nucleus
109
what causes platelets to contract?
actin, myosin and thrombosthenin
110
how are platelets able to make enzymes and store calcium?
residuals of both endoplasmic reticulum and Golgi apparatus
111
platelets have _____ to produce ATP and ADP
mitochondria and enzymes
112
platelets have an enzyme system to produce
eicosanoids (Thromboxane A2)
an activation molecule for platelet recruitment
113
platelet cytoplasm contains _____ for injury-damaged tissue growth
fibrin-stabilizing factor + a number of growth factors
114
haemostasis (prevention of blood loss) involves
vascular spasm/constriction (limits blood flow from small vessels)
formation of platelet plug
blood coagulation
growth of tissue to repair the injury (once blood loss has stopped)
115
haemostasis
stopping blood loss
116
vascular constriction during hemostasis results from a cut or rupture of a blood vessel due to
- local myogenic spasm - partially stimulated by thromboxane A2 (eicosanoid) released by platelets
- nervous reflex - initiated by activation of pain receptors
117
upon contact with damaged vascular endothelium (i.e., collagen), the surface glycoprotein receptors are activated and result in
platelet cell activation
118
what causes other platelet cells to be activated?
once activated, platelets produce ADP and thromboxane A2 which activate other platelet cells
119
release of ADP and thromboxane A2 in platelet activation pathway
1. platelet contact with collagen
2. platelet activation (releases ADP)
3. breaks down phospholipid (part of membrane) to produce arachidonic acid
4. arachidonic acid has two pathways: COX-II or lipoxygease
5. COX-II pathway: produces thromboxane A2
120
platelet activation pathway
1. platelet contact with collagen, activates glycoprotein receptors
2. activates production of ADP and thromboxane A2
3. ADP causes swellling and protruding processes that bind other platelets
4. thromboxane A2 activates other platelets and forms platelet plug + vasoconstriction of blood vessels in area
5. activated platelets produce fibrin-stabilizing factor, which forms fibrin meshwork + clot
121
what role does aspirin/endomethacin play in blood coagulation?
blocks COX-II to prevent production of thromboxane A2
this is why aspirin is used during heart attack to prevent blood thickening/clot formation
122
eicosanoids (thromboxane A2) are derived from
phospholipids and then arachidonic acid
123
arachidonic can go through 2 pathways
cyclooxygenase-II (COX-II) or lipoxygease
124
prostenoids are formed in the COX-II pathway and include
thromboxane, prostaglandins, prostacyclins
125
all of the eicosanoids produced by arachidonic acid (in COX-II and lipoxygease pathways)
COX-II: thromboxane, prostaglandins, prostacyclins
lipoxygease: leukotriene
126
formation of fibrin meshwork and clotting
activated platelets produce fibrin-stabilizing factor = forms fibrin meshwork + clotting
127
how does ADP act as a signalling molecule?
causes swelling and produces protruding processes that bind to other platelet cells (autocrine and paracrine process)
128
thromboxane A2 leads to formation of
a platelet plug - other platelet cells are activated and aggregate to form this
129
why is blood coagulation local?
we have a combination of coagulants and anti-coagulants in blood to prevent blood clots forming in unneeded areas
130
blood vessel trauma results in the activation of
extrinsic and intrinsic factors leading to the activation of thrombin by releasing tissue prothrombin activator
131
thrombin
key enzyme formed by cleavage of prothrombin
thrombin cleaves fibrinogen to form fibrin
132
prothrombin to thrombin
in liver due to vitamin K
1. prothrombin cleaved to fragment 1+2 and prethrombin-2
2. prethrombin-2 forms thrombin
133
2 roles of thrombin
cleaves fibrinogen to form fibrin monomers and activates fibrin-stabilizing factor which polymerizes fibrin threads/meshwork
134
what do platelet cells do to fibrin threads for clot formation
reinforce cross-linking between fibrin threads and release calcium (required for clot formation)
135
what does the fibrin meshwork do at the site of trauma?
holds platelets and blood cells together to form the clot and also adheres to damaged surfaces of blood vessel to prevent further blood loss
136
factors that initiate blood coagulation
factor III (tissue thromboplastin) and factor XII (Hagemen factor)
137
factor III
AKA tissue thromboplastin
initiates extrinsic pathway (lipoprotein + phospholipid); released from tissue following trauma
138
factor XII
AKA Hagemen factor
initiates intrinsic pathway; contact of this factor with platelet, collagen or wettable surface results in configuration change + activation which activates other factors and leads to clotting
139
what ion is blood coagulation dependent on
calcium
140
extrinsic pathway is initiated by
tissue thromboplastin (factor III)
141
intrinsic pathway is initiated by
Hageman factor (factor XII)
142
blood coagulation is highly localized because of
natural anticoagulants
143
examples of anticoagulants
glycocalyx, thrombomodulin, heparin
144
glycocalyx (anticoagulant)
mucopolysaccharide absorbed to inner surface of endothelium - repels the clotting factors and platelets
145
thrombomodulin (anticoagulant)
membrane protein expressed on the surface of endothelial cells - binds with thrombin and prevents coagulation
146
heparin (anticoagulant)
activate other factors that remove/destroy thrombin; also increase activity of antithrombin-III and thrombomodulin by 100-1000 fold (very potent)
