Basics Flashcards
What are the functions of blood?
- Transport
- O2, nutrients, hormones
- CO2
- metabolic waste - Hemostasis
- Regulation
- body temperature
- signal transmission
- acid/base homeostasis - Protection from pathogens
What is the average blood volume of an adult?
7% of TBW (70ml/kg)
Which equation can be used to calculate blood volume and for which patients?
> 35kg
Nadler equation
Give the Nadler equation for adult women
BV = (0.3669 × H3) + (0.03219 × W) + 0.6041
Give the Nadler equation for adult men
BV = (0.3561 × H3) + (0.03308 × W) + 0.1833
What is the estimated blood volume (ml/kg) for neonates?
80-85
What is the estimated blood volume (ml/kg) for 1m - 1y?
75-80
What is the estimated blood volume (ml/kg) for 13m - 2y?
85
What is the estimated blood volume (ml/kg) for 2 - 3y?
80
What is the estimated blood volume (ml/kg) for 4 - 6y?
76-77
What is the estimated blood volume (ml/kg) for 7 - 14y?
70-75
What are the constituents of blood?
55% plasma
45% blood cells
What does plasma contain?
Water
Plasma proteins
Electrolytes
Hormones
Bioactive substances
Which plasma protein is an important constituent of plasma?
Coagulation factors
What is the function of erythrocytes?
Transport O2 and CO2
Bicarbonate buffer system
Which antiporter mediates the membrane transport of CO2?
Cl-/HCO3- antiporter
What are the characteristics of an erythrocyte?
No nucleus or cell organelles
Biconcave shape
Contains hemoglobin
How does an erythrocyte produce energy?
Glycolysis and HMP shunt
What is an HMP shunt?
Hexose monophosphate shunt found in the pentose phosphate pathway which degrades G6P to provide NADPH and ribose for nucleotide synthesis
How much of the total WBC count consists of neutrophils?
60%
What is the function of neutrophils?
Acute inflammatory response
Phagocytosis
What are the characteristics of neutrophils?
Multilobed nucleus
Granules
- specific
- azurophilic
What do the azurophilic granules in neutrophils contain?
Myeloperoxidase
Proteinases
Acid phosphatase
Beta-glucuronidase
What do the specific granules in neutrophils contain?
LAP (leucocyte alkaline phosphatase)
Collegenase
What are a high versus low LAP score associated with?
High - incr mature WBC (myeloproliferative disorders)
Low - incr immature WBC (CML)
How much of the total WBC count consists of eosinophils?
1-3%
What is the function of eosinophils?
- Defense against parasitic infections
- Production of enzymes and proteins
- Phagocytosis of antigen-antibody complexes
What mediates the defensive function of eosinophils against helminths?
Major basic protein (MBP) production
Which enzymes and proteins do eosinophils produce?
Histaminase
Eosinophilic cationic protein
Eosinophil peroxidase
Eosinophil-derived neurotoxin
How much of the total WBC count consists of basophils?
0-0.75%
What is the function of basophils?
Mediates allergic reactions
Synthesis and release of leukotrienes
What are the characteristics of basophils?
Dense, basophilic granules
- heparin
- histamine
How much of the total WBC count consists of monocytes?
3-7%
What is the function of monocytes?
Differentiates into macrophages
Phagocytosis
What are the characteristics of monocytes?
Mononuclear cells
Kidney-shaped nucleus
Large, non-granulated cytoplasm with ground glass appearance
Which leukocyte type is the largest?
Monocyte
How much of the total WBC count consists of lymphocytes?
25-33%
What are the functions of lymphocytes?
80% T cells (adaptive cellular immune response)
15% B cells (adaptive humoral immune response)
5% NK cells (innate immune response)
What are the characteristics of lymphocytes?
Mononuclear cells
Round, densely staining nucleus
Small, pale cytoplasm
What do T cells differentiate into?
- Cytotoxic
- Helper
- Regulatory
Which receptors do cytotoxic T cells have?
CD8 (interact with MHC I)
Which receptors do helper T cells have?
CD4 (interact with MHC II)
Which receptors do regulatory T cells have?
CD4
CD25
FoxP3
What is the lifespan of a thrombocyte?
8-10d
What are the characteristics of thrombocytes?
Anucleate cytoplasmic discs derived from megakaryocytes
Approx 1/3 stored in spleen
Which granules do thrombocytes contain?
- Dense
- ADP
- Ca2+ - Alpha
- vWF
- fibrinogen
- fibronectin
What are the characteristics of macrophages?
Different in each tissue
Activated by y-interferon
What are macrophages found in the liver called?
Kupffer cells
What are macrophages found in connective tissue called?
Histiocytes
What is the function of macrophages?
- Phagocytosis
- bacteria
- RBCs
- cellular debris - Antigen presentation
- MHC II
What do mast cells originate from?
Basophils
What is the function of mast cells?
Binds Fc portion of IgE to membrane -> mast cell degranulation -> release of histamine, heparin, tryptase and eosinophil chemotactic factors
What are the characteristics of dendritic cells?
Derived from myeloid or lymphoid precursors
Express MHC II and Fc receptor
What is the function of dendritic cells?
- Phagocytosis
- Antigen-presenting cell (APC)
- Links innate and adaptive immune response
What are dendritic cells found in the skin referred to as?
Langerhans cells
What are the characteristics of plasma cells?
Eccentric nucleus
Clock-face appearance chromatin
Abundant rough ER
Well-developed Golgi
Do not circulate in peripheral blood
Which mnemonic can be used to remember the constituents of whole blood count?
Never Let Monkeys Eat Bananas
Neutrophils > leucocytes > monocytes > eosinophils > basophils
What is bone marrow?
Spongy, soft tissue within the hollow spaces of cancellous bone
What does bone marrow contain?
- Haematopoetic stem cells
- Stromal cells
What is the function of bone marrow?
Haematopoesis
Filtration of RBCs
Houses immune cells
What are the 2 types of bone marrow?
Red marrow
Yellow marrow
What is the location of red marrow?
Flat bones (sternum, skull, vertebrae, scapula, pelvic)
Long bones (metaphysis, epiphysis)
What is the location of yellow marrow?
Long bones (shaft and diaphysis)
What is the function of red marrow?
Haematopoesis
Turns into yellow marrow with age
What is the function of yellow marrow?
Not haematopoetic
Can become red marrow
What is the composition of red marrow?
- Haematopoetic compartment
- haematopoetic stem cells
- vascular compartment - Stroma
Which cells can transform red marrow into yellow marrow and how?
Adventitial reticular cells by accumulating fat
What are the stromal cells of bone marrow?
Adventitial reticular cells
Mesenchymal stem cells
Macrophages
Define haematopoesis
The process by which multipotent haematopoetic stem cells differentiate into myeloid/lymphoid precursor cells and eventually into mature blood cells
What do myeloid precursor cells differentiate into?
Erythroblasts
Megakaryoblasts
Monoblasts
Myeloblasts
What do lymphoid precursor cells differentiate into?
NK cells
B cells
T cells
What do myeloblasts differentiate into?
Neutrophil
Eosinophil
Basophil
Which growth factors are required for haematopoesis?
SCF
GM-CSF
G-CSF
M-CSF
EPO
TPO
What produces stem cell factor?
Stromal cells of BM
What produces granulocyte-monocyte colony-stimulating factor?
Endothelial cells
T cells
What produces granulocyte colony-stimulating factor?
Endothelial cells
Macrophages
What produces macrophage colony-stimulating factor?
Endothelial cells
Macrophages
What produces EPO?
Fibroblast-like interstitial cells surrounding peritubular capillaries of kidneys and hepatocytes
What produces TPO?
Liver (parenchymal cells and sinusoidal endothelial cells)
Kidney (PCT cells)
What is the therapeutic use of GM-CSF?
Sargramostim - synthetic recombinant drug
- treatment of neutropenia
- myeloid reconstitution after BMT
- myelodysplasia
- aplastic anemia
What is the therapeutic use of G-CSF?
Filgrastim - synthetic recombinant drug
- treatment of neutropenia
- BM recovery
What is the main site of erythropoiesis from week 3 - 8?
Yolk sac
Where is definitive haematopoiesis derived from?
Stem cells observed on dorsal aorta (aorta-gonads-mesonephros region)
What are the major haematopoetic organs from 6 weeks of fetal life to 6-7 months?
Liver and spleen
Bone marrow from month 6-7
What are the characteristics of a haemopoietic stem cell?
CD34 +ve
CD38 -ve
Lin-
Appearance of small/medium lymphocyte
How does assay of very early progenitors differ to late progenitors?
Very early - culture on bone marrow stroma
Late - semi-solid media
Name stromal cells
Adipocytes
Fibroblasts
Osteoblasts
Endothelial cells
Macrophages
What do stromal cells secrete?
Collagen
Glycoproteins
- fibronectin
- thrombospondin
Glycosaminoglycans
What are mesenchymal stem cells also known as?
- Multipotent mesenchymal stromal cells
- Adherent stromal cells
What enhances stem cell mobilisation?
Growth factors eg G-CSF
What enhances stem cell homing?
Chemokine gradient using stromal derived factor 1 (SDF-1)
What are the receptors on stem cells for jagged proteins on stroma?
KIT
NOTCH