Haematopoiesis, haematology, haemostasis (year 2) Flashcards
define haematopoiesis
production of blood cells
what tissue type are leucocytes, erythrocytes and platelets produced in?
haemopoietic tissue
where is the major site of haematopoiesis?
bone marrow
what blood cell has the longest lifespan?
erythrocytes
what is the average lifespan of an RBC?
1-5 months
how long is platelets lifespan?
10 days
how long do leucocytes live for?
hours to years depending on the type
what blood cells have the shortest lifespan?
neutrophils
what is the first thing that is noticed when there is a sudden arrest of haematopoiesis?
reduction in neutrophils (neutropenia)
where is the best site to collect bone marrow in dogs?
head of femur and humerus
what cells do all blood elements arise from?
stem cells
what are the types of stem cells?
totipotent
pluripotent
multipotent
unipotent
define totipotents
stem cells that are present in the embryo and can divide into any cell
define pluripotent
stem cells found in the blastocyst that can differentiate into almost all cells but not into an embryo
define multipotent
stem cell found in most tissues that can differentiate into a limited range of cells such as haematopoitic stem cells
define unipotent
stem cells that can only generate one type of cell
what can a multipoint haematopoietic stem cell differentiate into?
common myeloid progenerator
common lymphoid progenitor
name some cells that the common myeloid progenerator may differentiate into
erythrocytes
mast cells
megakaryocytes
myeloblast - basophil, eosinophil, monocyte, neutrophil
what can common lymphoid progenitor cells differentiate into?
NK cells
lymphocytes
what is lymphogenesis?
lymphocyte production
where does lymphogenesis being?
bone marrow
where do the later stages of lymphocyte maturation, proliferation and migration occur?
lymphoid organs
in a steady state in bone marrow which pool is expected to dominate?
maturation and storage
does granulopoiesis or monocytopoiesis occupy the majority of the haematopoetic tissue?
granulopoiesis
define granulopoiesis
production of granulocytes such as neutrophils, eosinophils and basophils
what is granulopoiesis and monocytopoiesis controlled by?
cytokines - mainly IL3 and growth factors
what are the three colony stimulating factors that control granulopoiesis and monocytopoiesis?
granulocyte-macrophage CSF
macrophage CSF
granulocyte CSF
what control growth factors and cytokines?
presence of inflammation/infection
activated T lymphocytes
neutrophils providing negative feedback on their production
what is the proliferative pool?
early mitotically active with a quarter of all granulocytes
what is the maturation pool in granulocytopoiesis?
later stages of granulopoiesis containing banded neutrophils
what cell dominated the storage pool of granulocytopoiesis?
segmented neutrophils
what is the only stage of neutrophils released from bone marrow?
segmented - presence of banded may be due to problems such as inflammation
what might inflammation cause an increase in in the blood?
neutrophils (neutrophilia) because of increased release from storage pool
what may very acute/severe inflammation cause to the happen to the neutrophils?
consumption of circulating and stored neutrophils causing neutropenia
what drives eosinopoiesis?
mainly IL5
what cell type is rare to see in circulation?
basophil and mast cells
where do basophils mature?
bone marrow
where do mast cells mature?
in the peripheral tissue but are derived from bone marrow
what are aged/damaged RBCs removed by?
macrophages
what is erythropoiesis mainly controlled by?
erythropoietin
what is require for erythropoiesis?
iron, copper, B2, B6, B12
do RBCs have the capability to repair themselves?
no they have no organelles
what stimulates erythropoietin?
hypoxia due to a decrease in RBCs or increased tissue demand or decreased oxygen availability
what organ releases erythropoietin?
kidney
how long does erythropoiesis take?
5 days
describe the process of erythropoiesis
large blasts divide to become smaller
haemoglobin concentration increases then cell division stops when optimal intracellular haemoglobin concentration is reached
nucleus is extruded
organelles and RNA is lost
how long does it take a juvenile erythrocyte to mature in blood?
24 hours
why are juvenile erythrocytes blue?
because they still have retained organelles
what is thrombopoeisis?
formation of platelets from a progenitor that gives rise to a megakaryocyte
how are platelets formed from a megakaryocyte?
fragmentation of megakaryocyte cytoplasm and shedding into blood
what mediates thrombopoeisis?
thrombopoietin
what organ produces thrombopoietin?
liver - constantly produced
what else other than thrombopoietin is able to stimulate thrombopoeisis?
IL6 during inflammation
iron deficiencies
how is thrombopoeisis self-regulated?
platelets lost/destroyed
more thrombopoetin available
increased thrombopoeisis
when might thrombocytosis be seen?
during inflammation or iron deficiency
what should a full haemogram include?
PCV (microhaematocrit tube) and total protein
blood counts
blood smear evaluation
what tube would you ideally collect a sample in for haematology?
EDTA tube
what colour top do EDTA tubes have?
purple
what must be avoided during sampling processing?
inadequate mixing haemolysed specimens lipaemic specimens (take fasted) clotted specimens platelet clumps diluted specimens
what blood counts should a full haemogram include?
total haemoglobin content haematocrit - equivalent to PCV RBC count RBC index reticulocyte count platelet coint total leukocyte count (differential leukocyte counts)
what are the differential leukocyte counts?
neutrophils lymphocytes monocytes eosinophils basophils
what is it called in either haemoglobin, haematocrit of RBC count is below the reference intervals?
anaemia
what is it called in either haemoglobin, haematocrit of RBC count is above the reference intervals?
erythroctosis
what should be taken into account when deciding if an animal is anaemic or has erythrocytosis?
age, hydration, species, , breed
what are the three main causes of anaemia?
inadequate production from bone marrow
increased destruction
increased loss
what are the two types of blood loss anaemia?
acute or chronic
what could cause blood loss anaemia?
haemorrhage - trauma, clotting disorder, bleeding lesion
blood-sucking parasites
blood loss anaemia is a proportional loss of all blood components, what are the two stages?
1 - initial decrease in blood volume
2 - activation of mechanism to maintain volaemia, influx of water so dilution of blood
what compensates during acute blood loss anaemia?
bone marrow is able to compensate loss by increasing erythropoiesis and red cell mass - normalises in 1-2 weeks
what is expected during acute blood loss?
decreased total protein
evidence of regeneration
what may chronic blood loss lead to the depletion of?
iron stores leading to an iron deficiency
how long does it take iron deficiency anaemia during chronic bleeding in adults?
at least 1 month of continuous bleeding
is chronic blood loss anaemia regenerative our non-regenerative?
either - non-regenerative after depletion of ion stores
what are the two classes of haemolysis?
immune mediated
non immune mediated
what may cause non immune mediated haemolytic anaemia?
oxidative damage, intra-erythrocytic parasites, bacteria, viruses, mechanical damage
where can haemolysis occur?
extravascular or intravascular
what mediates extravascular haemolysis?
macrophages on tissue
what occurs if the liver capacity of bilirubin is overwhelmed?
hyperbilirubinaemia
jaundice
what occurs if there is intravascular haemolysis?
haemoglobinuria
red urine
how is anaemia classified based of the haemogram?
degree of severity
regenerative response
erythrocyte index
what are the classes of the degree of severity of anaemia based on haemograms?
mild (30-36%)
moderate
severe (less than 18%)
what its classified by the erythrocyte index of a haemogram?
microcytic, normocytic, macrocytic
hypochromic, normochromic
what is described by microcytic, normocytic and macrocytic?
size of the RBC
what is described by hypochromic and normochromic?
colour of RBC - whether it has the correct haemoglobin concentration
why does anaemia need to be classified?
understand the underlying pathophysiological mechanisms
if regenerative anaemia is present what is functioning normallY?
bone marrow
define regenerative anaemia
decrease oxygen carrying capacity leads to erythropoiesis by bone marrow to release higher number of juvenile RBCs into circulation
define non-regenerative anaemia
bone marrow fails to respond to decreased oxygen carrying capacity
what types of anaemia is generally regenerative?
blood loss
haemolysis
what types of anaemia is generally non-regenerative?
iron deficiency chronic disease/inflammation drugs bone marrow disease endocrine disorders pre-regenerative
how is regeneration assessed?
quantification of young erythrocytes in circulation
bone marrow examination
how do young erythrocytes compared to older ones?
darker as they have more organelles
what is MCV in the erythrocyte index?
mean corpuscular volume
average RBC size
what is MCHC in the erythrocyte index?
mean corpuscular Hb concentration
average haemoglobin concentration of RBCs
what is MCH in the erythrocyte index?
mean corpuscular Hb
average amount if haemoglobin per cell
if the MCV is raised what does this mean you have?
macrocytic anaemia
what is macrocytic anaemia usually due to?
presence of larger cells which are usually juvenile erythrocytes
if macrocytic anaemia usually regenerative or non-regenerative?
regenerative
what is reduced MCV known as?
microcytic anaemia
what is microcytic anaemia usually due to?
smaller cells due to less haemoglobin due to an iron deficiency
is normocytic anaemia usually regenerative or non-regenerative?
usually non-regenerative but can be regenerative
is normochromic anaemia usually regenerative or non-regenerative?
non-regenerative but may be regenerative
is hypochromic anaemia usually regenerative or non-regenerative?
regenerative as juvenile RBCs have less haemoglobin but can be due to iron deficiency
what is raised MCHC (hyperchromic) anaemia due to?
almost always artifactual
what are the 5 major leucocytes in circulation?
neutrophil, monocyte, lymphocyte, eosinophil, basophil
what leucocytes are involved in the innate immune system?
neutrophil, monocyte
what leucocytes are involved in the adaptive immune system?
lymphocytes
what leucocytes are involved in defence against parasites and allergy?
eosinophils, basophils
what leucocytes are granulocytes?
neutrophil, eosinophil, basophil
what is a low leucocyte count called?
leucopenia
what is a high leucocyte count called?
leukocytosis
what may make the WBC count by an automated machine less accurate?
if the WBCs are clumped in a blood clot
if there are lot of nucleated RBCs
where is not a good area of a blood smear to do a leucocyte count and why?
feathered edge - most will be destroyed
how is absolute number calculated from the differential leucocyte count?
% x WBC count
what is the term given to a neutrophil count that is above the upper reference limit?
neutrophilia
what are two common situations when neutrophilia is seen?
inflammation stress leucogram (stress or steroid administration)
what is neutrophilia from a stress leucogram usually combined with?
lymphopenia, monocytosis, eosinopenia
what is neutropenia?
neutrophil count below the lower reference limit
what are two common causes of neutropenia?
severe overwhelming inflammation
bone marrow disease
what may cause bone marrow disease?
toxic insult
neoplasia
parvo and other viruses
immune mediated destruction of precursors
what is left shift when describing neutrophil numbers?
increase in the number of juvenile neutrophils
what are common causes of left shift neutrophilia?
severe inflammation - bacterial infection, immune mediated disease
what is monocytosis?
monocyte count about the upper reference limit
what are the common causes of monocytosis?
acute/chronic inflammation, tissue damage, necrosis
stress leucogram
leukaemia (extreme)
what is a lymphocyte count above the upper reference limit known as?
lymphocytosis
what are the common causes of lymphocytosis?
chronic inflammtion
adrenalin release in cats
leukaemia
what is a lymphopenia?
lymphocyte count below the lower reference limit
when is a lymphopenia commonly seen?
chronic inflammation
stress leucogram
viral disease
what is an eosinophil count above the upper reference limit called?
eosinophilia
when may an eosinophilia be seen?
parasitic infection
allergy
hypersensitivity
what are platelets?
cytoplasmic fragments of megakaryocytes
what are some common causes of thrombocytopenia?
increased destruction
increased consumption
decreased production
redistribution
what are two main features haemostasis helps to maintain?
vascular integrity
blood fluidity
define primary haemostasis
this is the formation of a primary platelet plug
what is required for primary haemostasis to occur?
vascular endothelial damage
what does damage to vascular endothelial lead to the exposure of?
subendothelial collagen
what is released that inducing rolling in platelets and leucocytes?
P-selectin
what does con Willebrand factor bind to?
collagen and platelets
what are the functions of platelets?
adhesion aggregation secretion procoagulant surface clot retraction
what receptors allow platelets to adhere to endothelium?
GPI
what do GPI receptors bind to?
collagen or von Willebrand factor
what allows platelet to platelet aggregation?
fibrinogen or von Willebrand factor
what substances can platelets release after activation?
thromboxan serotonin factorV ADP ATP plasminogen
what produces von Willebrand factor?
endothelial cells
what is von Willebrand factor?
large multimeric plasma protein
what does von Willebrand factor serve as a carrier of?
factor VIII
what needs to happen once the primary platelet plug has formed in small defects?
nothing only primary haemostasis is required
what needs to happen to the primary platelet plug has formed in large defects?
the plug requires fibrin stabilisation - secondary haemostasis
what is secondary haemostasis?
formation of a definitive clot - coagulation
what is soluble fibrinogen converted to?
insoluble fibrin
what is the conversion of fibrinogen to fibrin mediated by?
thrombin
what substances makes the platelet plug more stable?
fibrin crosslinkage
what is thrombin generation initiated and sustained by?
initiated - exposure to subendothelium
sustained - coagulation cascade
what is the coagulation cascade?
series of enzyme activating steps resulting in thrombin and insoluble fibrin formation
what is the aim of the coagulation cascade?
form insoluble fibrin
what is factor I in the coagulation cascade?
fibrinogen
what is factor II in the coagulation cascade?
prothrombin
what is factor III in the coagulation cascade?
tissue factor
what is factor IV in the coagulation cascade?
free calcium
what are the three things that most steps of the coagulation cascade involve?
enzyme
substrate
cofactor
what letter can the coagulation cascade be simplified into?
Y
what is the long arm of the Y in the coagulation cascade?
intrinsic pathway
what is the short arm of the Y in the coagulation cascade?
extrinsic pathway
what is the base of the Y in the coagulation cascade?
common pathway
what is the extrinsic pathway of the coagulation cascade activated by?
extravascular causes (tissue factor) - things that shouldn’t be in circulation but are due to damage of endothelium
what factor does tissue factor stimulate?
factor VII
what is the intrinsic pathway of the coagulation cascade activated by?
intravascular causes - exposure of damaged endothelium
what factor does the intrinsic pathway start with?
XII
what are the factors in the intrinsic pathway? (in order of activation)
XII
XI
IX
VIII
what is the most important pathway to start coagulation?
extrinsic
what is the most important pathway to amplify coagulation?
intrinsic
what factor does the common pathway begin with?
factor X
what are the factors of the common pathway of the coagulation cascade? (in order)
X
V
II
I
what laboratory tests are used to test the intrinsic and common pathway?
PTT
what tests are used to test the extrinsic and common pathway?
PT (prothrombin time)
what test tests the the fibronogen to fibrin step in the coagulation cascade is functional?
TT (thrombin time)
where are most coagulation factors produced?
liver - not von Hillebrand factor
what are the non-enzymatic coagulation factors?
III
I
V
VIII
what are the vitamin K dependant coagulation factors?
II
VII
IX
X
what do vitamin K dependent coagulation factors require for activity?
carboxylation - this enzyme if vitamin K dependent
what are the two functions that stop indefinite clotting?
dissolution of clot (fibrinolysis)
natural anticoagulants
what is tertiary haemostasis?
fibrinolysis
when does the fibrinolytic pathway begin?
when coagulation starts
what is the fibrinolytic pathway mediated by?
plasmin
what is activated to form plasmin?
plasminogen
what are some examples of natural anticoagulants?
intact enodthelium
antithrombin III
protein C
tissue factor pathway inhibitor
what does antithrombin III bind to and inactivate?
thrombin (some other factors as well)
where is antithrombin III produced?
liver
what is the action of antithrombin III enhanced by?
heparin (from mast cells)
