Hematology Flashcards
(209 cards)
1
Q
What percentage of total body weight is water?
A
Around 57%, approximately 40 L in a 70 kg man
2
Q
What are the two main body fluid compartments?
A
Intracellular (~28 L) and Extracellular (~14 L)
3
Q
How is the extracellular fluid distributed?
A
Interstitial (~11 L), plasma (~3 L), and small compartments such as cerebrospinal fluid, intraocular fluid and fluids of the GI tract
4
Q
Which ions predominate in the intracellular fluid?
A
Potassium (K⁺) and phosphate (HPO₄²⁻)
5
Q
Which ions predominate in the extracellular fluid?
A
Sodium (Na⁺) and chloride (Cl⁻)
6
Q
What factors affect membrane permeability?
A
Osmotic gradient and molecular size
7
Q
What does body water volume change with?
A
Age, sex, obesity
8
Q
Blood volume of water in women vs men
A
5L in women and 5.5 in men
9
Q
How does prolonged heavy exercise affect water output?
A
Increases breathing and sweat; decreases urine
10
Q
What is total water output with exercise vs. normal?
A
Exercise: ~6600 mL/day; Normal: ~2300 mL/day
11
Q
Why is calcium (Ca²⁺) low in cytoplasmic analysis?
A
It’s stored in organelles like the ER and Golgi
12
Q
What are the functions of intracellular fluid?
A
Nutrient transport, waste removal, ion balance, fluid is occupying the space within the cells (i.e., cytoplasm)
13
Q
What is the role of extracellular fluid?
A
Transports nutrients, oxygen, and waste between cells and blood
14
Q
What are the components of ECF?
A
Interstitial fluid, plasma, and small fluid compartments
15
Q
What ions predominate in ECF?
A
Sodium (Na⁺) and chloride (Cl⁻)
16
Q
What is interstitial fluid derived from?
A
Capillary filtration
17
Q
How is ISF different from plasma?
A
Lower concentration of large proteins due to selective permeability
18
Q
What is the function of ISF?
A
Fills spaces between cells; facilitates exchange with blood
19
Q
Relative permeability
A
Size determines movement and movement determined by osmotic pressure
20
Q
What is the relationship between molecule size and permeability?
A
Inverse relationship
21
Q
Average size of pores
A
~6-7 nM, they are larger in liver (liver is leaky) and smaller in brain
22
Q
What determines the movement of fluid across membranes?
A
Osmotic pressure and molecular size
23
Q
What happens when a solution is hyperosmotic?
A
Water moves into the solution
24
Q
What happens when a solution is hypoosmotic?
A
Water moves out of the solution
25
What happens as molecular weight increases?
Endothelial permeability decreases
26
Why is selective permeability important?
It regulates fluid balance and maintains homeostasis
27
What causes colloid osmotic (oncotic) pressure?
Plasma proteins
28
How does protein concentration affect oncotic pressure?
Higher protein = higher oncotic/ osmotic pressure
29
In which direction does water move in response to oncotic pressure?
From low protein (low pressure) to high protein (high pressure)
30
What is the normal total oncotic pressure in plasma?
28 mmHg
31
What are the contributions of plasma proteins to oncotic pressure?
- Albumin: 21.8 mmHg
- Globulin: 6 mmHg
- Fibrinogen: 0.2 mmHg
32
What is the function of albumin?
Provides most of the plasma’s oncotic pressure and acts as a nonspecific carrier protein
33
What is the function of globulins?
Specific functions: carrier proteins, enzymes, immunoglobulins
34
What is the function of fibrinogen?
Key for blood clotting; forms long fibrin threads during coagulation
35
Which one forms stable coagulated blood?
Fibrinogen
36
Which protein is plasma is the most abundant?
Albumin
37
What forces regulate capillary fluid movement?
Hydrostatic pressure and oncotic pressure (Starling forces)
38
What do Starling forces determine?
Inward and outward pressure between capillaries and interstitial fluid
39
What is capillary hydrostatic pressure (Pc)?
Pressure exerted by blood inside capillaries that pushes fluid out into the interstitial space
40
What is interstitial hydrostatic pressure (Pi)?
Pressure in the interstitial fluid that pushes fluid back into capillaries (usually low due to gel-like matrix)
41
What is capillary oncotic pressure (πc)?
Pulling force by plasma proteins (mainly albumin) that draws fluid into the capillaries
42
What is interstitial oncotic pressure (πi)?
Pulling force by interstitial proteins that draws fluid out of capillaries
43
What is the formula for net filtration pressure?
Net Filtration = +Pc - Pi - πc + πi
44
What does a positive net filtration pressure mean?
Filtration: fluid moves out of capillaries
45
What does a negative net filtration pressure mean?
Reabsorption: fluid moves into capillaries from the interstitial space
46
Why is capillary oncotic pressure (πc) higher than interstitial oncotic pressure (πi)?
Because proteins are large and cannot pass freely through capillary walls, leading to protein accumulation inside capillaries
47
What proteins are found in the interstitial space and do they contribute to oncotic pressure?
Structural proteins like collagen and proteoglycans, but they contribute minimally to oncotic pressure
48
What happens when filtration exceeds reabsorption consistently?
Edema – fluid accumulates in tissues due to imbalance in Starling forces
49
Why is the balance of hydrostatic and oncotic pressures important?
It regulates tissue hydration and prevents fluid buildup (edema) or dehydration
50
What is the main force responsible for pushing fluid out of capillaries?
Capillary hydrostatic pressure (Pc) – it drives fluid from capillaries into tissues
51
What additional force contributes to filtration besides hydrostatic pressure?
Interstitial oncotic pressure (πi) – it pulls fluid out of capillaries
52
Where in the capillary is filtration most dominant?
At the arterial end – where hydrostatic pressure is highest
53
What is the main force pulling fluid back into capillaries?
Capillary oncotic pressure (πc) – mainly due to plasma proteins like albumin
54
How does interstitial hydrostatic pressure (Pi) affect fluid movement?
It pushes fluid into the capillary, aiding reabsorption
55
Where in the capillary is reabsorption most dominant?
At the venous end – hydrostatic pressure drops, allowing oncotic pressure to dominate
56
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)
57
Inward pressure on capillaries is determined by
Plasma colloid osmotic pressure = PULL (high protein concentration in plasma) + interstitial fluid pressure = PUSH
58
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
59
Which compartment is gaining fluid in this scenario?
The interstitial compartment
60
What are the main components of the interstitial compartment?
Collagen fibers, proteoglycan filaments, interstitial fluid (tissue gel), and ~1% free-flowing water
61
What forms the gel-like structure in the interstitial space?
Proteoglycan filaments (~98% hyaluronic acid) trap interstitial fluid, forming tissue gel
62
How much of the interstitial fluid is free-flowing?
~1% is free-flowing; the rest is trapped in the gel
63
How do solutes move in the interstitial compartment?
By molecular diffusion through the tissue gel (95–99% as fast as in free fluid)
64
What condition results from increased fluid in the interstitial compartment?
Edema, which causes tissue swelling due to excess free fluid from changes in osmotic colloid pressure
65
What protein dominates the structure of the interstitial matrix?
Collagen – the main structural protein
66
Proteoglycan filaments are made up of
98% hyaluronic acid (traps water) and 2% protein
67
What role does the interstitial gel play in fluid distribution?
Ensures uniform fluid distribution regardless of body position; resists gravity due to gel consistency
68
How does the gel structure affect intracellular distance?
Maintains consistent spacing between cells to optimize solute and gas diffusion
69
What provides mechanical support in the interstitial compartment?
Collagen fibers and the gel matrix, supporting tissue structure and resisting external forces
70
What causes fluid movement from the interstitial space into the lymphatic system?
A small pressure gradient (~0.3 mmHg) drives one-way flow into lymphatic vessels
71
Why is lymphatic drainage important for fluid balance?
It prevents fluid accumulation in tissues by returning interstitial fluid to circulation
72
What is the primary function of the lymphatic system?
It serves as an accessory route for transporting fluid and macromolecules from interstitial space to veins
73
How is lymph filtered before reaching the bloodstream?
Through lymph nodes containing phagocytic cells that remove contaminants
74
What ensures one-way movement of lymph?
Valves and muscle contractions push lymph forward; there's no significant resistance
75
What causes lymphedema?
Blockage of lymphatic vessels, often from parasitic infections (e.g., Elephantiasis), or damage
76
What is lymphadenopathy?
Swelling of lymph nodes due to immune response from bacterial or viral infection
77
How does Elephantiasis affect lymph flow?
Filarial worms block lymph flow → fluid accumulation → tissue necrosis due to lack of oxygen
78
Is solute concentration higher in arterial or venous blood system?
Arterial
79
What is the volume and function of cerebrospinal fluid (CSF)?
~150 mL; provides cushioning for the brain and spinal cord
80
What does intraocular fluid do?
Maintains intraocular pressure (~15 mmHg) to keep the eyeball distended
81
Pressure of intraocular fluid
15 mmHg; maintains sufficient pressure in eyeball to keep it distended - tightly regulated to prevent glaucoma or blindness
82
Volume of fluid compartment of the GI tract
Potential space = 15 mL under normal conditions
83
Volume of fluid compartment (pleural cavity) of the lung
Mucoid fluid = 10 mL - Provides lubrication for easy movement of lung
84
Some examples of small fluid compartments
Pericardial cavity (heart), peritoneal cavity (intestine, stomach, liver), joint spaces, bone and cartilage
85
What is haemopoiesis?
The production of blood cells from hematopoietic stem cells (HSCs) in the bone marrow
86
What are committed progenitor cells?
Cells derived from HSCs that are committed to a specific lineage and must complete differentiation
87
What role do cytokines play in haemopoiesis?
They regulate the proliferation and differentiation of blood cells
88
All blood cells originate from the process of
Differentiation of pluripotential hemopoietic stem cells
89
Which cytokines promote the survival of all hematopoietic stem cells?
Interleukins and Stem Cell Factor (SCF)
90
What does Erythropoietin (EPO) stimulate?
Differentiation into erythrocytes (red blood cells)
91
What does Thrombopoietin (TPO) stimulate?
Differentiation into megakaryocytes, which form platelets
92
What do Granulocyte-Monocyte Colony-Stimulating Factors promote?
Differentiation into granulocytes and monocytes
93
What are the two major lineages of blood cells?
Myeloid and Lymphoid stem cell-derived lineages
94
What is the origin of all blood cells?
Hematopoietic stem cells (HSCs) in the bone marrow
95
What are the myeloid-derived blood cells?
Erythrocytes, platelets, and most leukocytes (granulocytes and monocytes)
96
What is the function of erythrocytes (RBCs)?
Transport oxygen
97
What is the function of platelets (thrombocytes)?
Clot formation and prevention of bleeding
98
What is the function of neutrophils?
Phagocytosis, first responders in infection
99
What is the role of eosinophils?
Defense against parasites and involvement in allergic reactions
100
What do basophils do?
Release histamine, important in inflammatory and allergic responses
101
What do monocytes become when they migrate to tissues?
Macrophages and dendritic cells
102
What do B lymphocytes do?
Differentiate into plasma cells that produce antibodies
103
What do T lymphocytes do?
Mediate adaptive immunity (e.g., helper and cytotoxic T cells)
104
What is the function of Natural Killer (NK) cells?
Destroy virus-infected and cancerous cells (innate immunity)
105
What types of cells come from the myeloid lineage?
Erythrocytes, Platelets, Neutrophils, Eosinophils, Basophils, Monocytes
106
Which myeloid cells are involved in blood clotting?
Platelets (Thrombocytes)
107
Which myeloid cells are granulocytes?
Neutrophils, Eosinophils, Basophils
108
Which myeloid cells are agranulocytes?
Monocytes
109
What types of cells come from the lymphoid lineage?
B lymphocytes, T lymphocytes, Natural Killer (NK) cells
110
What is the function of B cells?
Differentiate into plasma cells that produce antibodies
111
What is the function of T cells?
Mediate adaptive immunity (e.g., helper T and cytotoxic T cells)
112
What is the function of NK cells?
Innate immunity; kill virus-infected and tumor cells
113
Once the cell is committed, is tis process reversible or irreversible?
Irreversible
114
Do mature red blood cells have a nucleus?
No, mature RBCs are anucleate
115
What is the shape and size of a red blood cell?
Biconcave disc, ~8 μm diameter, 1–2 μm thick
116
Why is the biconcave shape important?
It increases surface area and allows flexibility to pass through capillaries
117
What is hematocrit?
The percentage of blood volume occupied by RBCs
118
What happens to hematocrit in severe anemia?
It can drop to ~10%, potentially fatal
119
What molecule do RBCs transport?
Hemoglobin (Hb)
120
What are the main functions of RBCs?
1. Transport of hemoglobin
2. Hemoglobin also acts as an important acid-base buffer for the blood
3. RBC contains carbonic anhydrase which catalyzes production of bicarbonate
121
What reaction does carbonic anhydrase catalyze?
CO₂ + H₂O → H₂CO₃ → HCO₃⁻ + H⁺
122
Where are red blood cells produced after birth?
In the bone marrow from pluripotent hematopoietic stem cells (PHSC)
123
What are the committed cells that become erythrocytes called?
Colony-forming unit erythrocyte (CFU-E)
124
What is the first committed erythroid precursor in bone marrow?
Proerythroblast – It is mitotic
125
What happens during the basophilic erythroblast stage?
The cell is still mitotic and hemoglobin starts to appeaR
126
What is characteristic of the polychromatophilic erythroblast?
It is mitotic and contains lots of hemoglobin
127
What occurs during the orthochromatic erythroblast stage?
The cell is not mitotic, hemoglobin increases, and the nucleus condenses and is about to be expelled
128
What is the reticulocyte stage?
Reticulocytes are immature RBCs, they are nucleated and enter circulation
129
What happens in the final stage of RBC maturation?
The mature erythrocyte has no nucleus or organelles and is fully functional for oxygen transport
130
Phases of a production of erythrocytes
1. Proerythroblast
2. Basophil erythroblast
3. Polychromatophil erythroblast
4. Reticulocyte
5. Erythrocytes
131
When does th erbc enter the circulation?
When they are a reticulocyte
132
After birth, where are RBCs produced?
After birth, RBCs are produced exclusively in the bone marrow from pluripotent hematopoietic stem cells (PHSC). This process declines with age
133
What are the two main components of hemoglobin?
Heme and globin
134
What is the most common form of hemoglobin in adults?
Hb A (2α + 2β)
135
How does fetal hemoglobin differ from adult hemoglobin?
Fetal hemoglobin is HbF (2α + 2γ), which has a greater affinity for O2 and can carry 20-30% more O2
136
Why does fetal hemoglobin have a higher affinity for oxygen?
It allows the fetus to compete with maternal blood to get enough oxygen
137
How many O₂ molecules can one hemoglobin molecule carry?
One hemoglobin molecule can carry four O₂ molecules because it has four Fe²⁺ ions, and each Fe²⁺ binds one O₂
138
What happens if carbon monoxide binds to hemoglobin?
Carbon monoxide binds irreversibly to the Fe²⁺ in hemoglobin, preventing it from carrying oxygen
139
What is the molecular basis of sickle cell anemia?
A mutation in the hemoglobin gene changes the glutamate to valine, altering the hemoglobin structure
140
What is one advantage of sickle cell anemia?
People with sickle cell anemia have some resistance to malaria
141
How many O₂ molecules can each hemoglobin (Hb) molecule carry?
Each hemoglobin (Hb) molecule can carry four O₂ molecules, as it contains four heme groups, each binding one O₂ molecule
142
What type of bond is formed between Fe²⁺ and O₂ in hemoglobin (Hb)?
The Fe²⁺ and O₂ bond in hemoglobin (Hb) is a loose, reversible bond
143
What happens to the conformation of the RBC when O2 comes off in sickle cell anemia?
In sickle cell anemia, when O₂ is released, mutated hemoglobin causes RBCs to sickle, becoming rigid and crescent-shaped, which disrupts blood flow
144
Why does kidney removal usually lead to anemia?
Kidney removal reduces erythropoietin (EPO) production, which lowers red blood cell production, causing anemia
145
Where is erythropoietin produced?
Erythropoietin is mainly produced in the kidney (80-90%)
146
What stimulates the production of erythropoietin?
Low oxygen levels (hypoxia) stimulate the production of erythropoietin
147
How long does it take for erythropoietin to stimulate RBC production?
It takes about 5 days for erythropoietin to stimulate the production of proerythroblasts and RBCs
148
What happens if there is a deficiency of Vitamin B12 or folic acid?
A deficiency leads to impaired DNA synthesis and nuclear maturation, causing megaloblastic anemia
149
What is the effect of a lack of Vitamin B12 on RBCs?
The lack of Vitamin B12 causes cells to fail to progress from the G2 phase to mitosis, leading to enlarged RBCs
150
What is the total body content of iron?
The total body content of iron is 4g
151
Where is iron stored in the body?
Iron is stored as ferritin, mainly in the liver, making up 15-30% of total body iron
152
How does transferrin contribute to RBC production?
Transferrin binds to iron, transports it to erythroblasts in the bone marrow, and helps deliver iron to mitochondria for heme synthesis
153
What limits the absorption of iron from the intestine?
The saturability of transferrin in the blood limits iron absorption from the intestine
154
What causes megaloblastic anemia (cells gain size but don't divide)?
Impaired absorption of vitamin B12
155
Abnormalities in transferrin result in
anemia
156
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
157
Average lifetime of RBC
~120 days (4 months)
158
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
159
What happens to RBCs as they age?
Their metabolic capability deteriorates, leading to membrane weakening and rupture
160
What happens to damaged RBCs?
They are phagocytosed by macrophages. Iron binds to transferrin for hemoglobin synthesis, and the porphyrin portion is converted to bilirubin, which is released into the blood and bile
161
How is bilirubin related to RBC destruction?
Bilirubin is a breakdown product of hemoglobin from destroyed RBCs and can be used to assess anemia or RBC destruction problems
162
What are platelets derived from?
Platelets are derived from megakaryocytes in the bone marrow
163
Do platelets have a nucleus?
No
164
Function of platelets
Blood clotting and wound healing
165
What do platelets contain?
Actin, myosin, thrombosthenin, enzymes, mitochondrias, and storage for Ca2+ and growth factors
166
What is the role of thromboxane A2 in platelets?
Thromboxane A2 is produced by platelets and plays a role in vasoconstriction and platelet aggregation
167
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
168
How are platelets able to make enzymes and store calcium?
Residuals of both endoplasmic reticulum and Golgi apparatus
169
Platelets have _ to produce ATP and ADP
Mitochondria and enzymes
170
Platelet cytoplasm contains _ for injury-damaged tissue growth
Fibrin-stabilizing factor + a number of growth factors
171
Haemostasis
Stopping blood loss
172
What are the four steps of haemostasis?
1) Vascular spasm, 2) Platelet plug formation, 3) Blood coagulation, 4) Tissue repair
173
What causes vascular spasm during haemostasis?
Local myogenic spasm (stimulated by thromboxane A2) and nervous reflex from pain receptors
174
When are platelets activated?
Upon contact with damaged vascular endothelium
175
What substances are released by activated platelets?
ADP and thromboxane A2
176
What does ADP do in platelet activation?
Causes platelet swelling and formation of sticky projections to bind other platelets
177
What is the role of thromboxane A2 in platelet activation?
It activates additional platelets, promoting aggregation
178
What stabilizes the platelet plug into a clot?
Fibrin-stabilizing factor produced by activated platelets
179
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
180
Upon contact with damaged vascular endothelium (i.e., collagen), the surface glycoprotein receptors are activated and result in
Platelet cell activation
181
what causes other platelet cells to be activated?
Once activated, platelets produce ADP and thromboxane A2 which activate other platelet cells
182
Release of ADP and thromboxane A2 in platelet activation pathway
Platelet contact with collagen
platelet activation (releases ADP)
breaks down phospholipid (part of membrane) to produce arachidonic acid.
Arachidonic acid has two pathways: - COX-II or lipoxygease
- COX-II pathway: produces thromboxane A2
183
Platelet activation pathway
Platelet contact with collagen, activates glycoprotein receptors
activates production of ADP and thromboxane A2
ADP causes swellling and protruding processes that bind other platelets thromboxane A2 activates other platelets and forms platelet plug + vasoconstriction of blood vessels in area, activated platelets produce fibrin-stabilizing factor, which forms fibrin meshwork + clot
184
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
185
Eicosanoids (thromboxane A2) are derived from
Phospholipids and then arachidonic acid
186
Arachidonic can go through 2 pathways
Cyclooxygenase-II (COX-II) or lipoxygease
187
Prostenoids are formed in the COX-II pathway and include
Thromboxane, prostaglandins, prostacyclins
188
All of the eicosanoids produced by arachidonic acid (in COX-II and lipoxygease pathways)
COX-II: thromboxane, prostaglandins, prostacyclins
lipoxygease: leukotriene
189
Formation of fibrin meshwork and clotting
Activated platelets produce fibrin-stabilizing factor = forms fibrin meshwork + clotting
190
How does ADP act as a signalling molecule?
Causes swelling and produces protruding processes that bind to other platelet cells (autocrine and paracrine process
191
Thromboxane A2 leads to formation of
A platelet plug - other platelet cells are activated and aggregate to form this
192
Why is blood coagulation local?
We have a combination of coagulants and anti-coagulants in blood to prevent blood clots forming in unneeded areas
193
Blood vessel trauma results in the activation of
Extrinsic and intrinsic factors leading to the activation of thrombin by releasing tissue prothrombin activator
194
Thrombin
Key enzyme formed by cleavage of prothrombin
Thrombin cleaves fibrinogen to form fibrin
195
Prothrombin to thrombin
In liver due to vitamin K
- Prothrombin cleaved to fragment 1+2 and prethrombin-2
prethrombin-2 forms thrombin
196
2 roles of thrombin
Cleaves fibrinogen to form fibrin monomers and activates fibrin-stabilizing factor which polymerizes fibrin threads/meshwork
197
What do platelet cells do to fibrin threads for clot formation
Reinforce cross-linking between fibrin threads and release calcium (required for clot formation)
198
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
199
Factors that initiate blood coagulation
Factor III (tissue thromboplastin) and factor XII (Hagemen factor)
200
Factor III
- AKA tissue thromboplastin
- Initiates extrinsic pathway (lipoprotein + phospholipid); released from tissue following trauma
201
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
202
What ion is blood coagulation dependent on
Calcium
203
Extrinsic pathway is initiated by
Tissue thromboplastin (factor III)
204
Intrinsic pathway is initiated by
Hageman factor (factor XII)
205
Blood coagulation is highly localized because of
Natural anticoagulants
206
Examples of anticoagulants
glycocalyx, thrombomodulin, heparin
207
Glycocalyx (anticoagulant)
Mucopolysaccharide absorbed to inner surface of endothelium - repels the clotting factors and platelets
208
Thrombomodulin (anticoagulant)
Membrane protein expressed on the surface of endothelial cells - binds with thrombin and prevents coagulation
209
Heparin (anticoagulant)
Activate other factors that remove/destroy thrombin; also increase activity of antithrombin-III and thrombomodulin by 100-1000 fold (very potent)
