respiratory 1 Flashcards
what is the stimulus for erythropoiesis and what occurs
hypoxia is the main stimulus
erythropoietin is the principle growth factor promoting viability, proliferation and differentiation
what are the sources of erythropoietin and what other growth factors work with it
○ Adults - kidney and to a lesser degree in the liver
○ Foetus - liver
○ e.g. stem cell factor, IL-3, thrombopoietin, androgens, glucocorticoids, growth hormone, thyroid hormone, insulin and IGF-1
what inhibits erythropoiesis
inflammation by reducing erythropoietin and its effect on the stem cells
- Mild anaemia
erythropoiesis what is the mother cell, what cells undergo mitotic divisions and what undergo maturation phase, how long does differentiation take
Rubriblast - mother cell
Rubriblast - Rubricyte
Maturation phase - from Rubricyte - Polychromatophil
mature erythrocyte nucleus is removed by macrophage
takes 3-5days under influence of erythropoietin
what occurs during maturation of red blood cells
1) haemoglobin increases
2) nucleus condenses
3) nucleus is then removed by macrophage
4) less blue more purple
how to tell if an animal is anaemic
↓ Haematocrit/Packed Cell Volume
↓ Erythrocyte/RBC count
↓ Haemoglobin level
- If any of these are low then it is anaemia
what are the 2 main causes of anaemia and what will occur in response
1) red cell loss -
1. haemorrhage
2. haemolysis
regenerative response
2) decreased red cell production - non regenerative response
what are some clinical signs of anaemia and more chronic signs
- Weakness and lethargy
- Pale mucous membranes - anaemic or circulatory disorder causing it
- Tachycardia
- Tachypnoea - faster respiratory rate
In severe cases can see - Cool extremities
- Weak peripheral pulses
- Heart Murmur
- Icterus - jaundice
- Shock
what are the classifications of regenerative and non-regenerative anaemia in terms of blood smear
Regenerative = marrow response evident - Reticulocytosis - Polychromasia - Hypochromic macrocytic anaemia Non-regenerative = no marrow response - Pre-regenerative or non-regenerative - No reticulocytosis, minimal polychromasia - Normocytic normochromic or hypochromic microcytic anaemia
what are the 5 ways in which we can assess for regeneration
1) blood smear
2) reticulocytosis = more acurate - need methylene blue staining
3) macrocytosis and hypochromasia - large erythrocytes with less haemoglobin however normocytic normochromic doesnt mean not regnerative
4) bone marrow evaluation
5) serial monitoring of PCV/CBC to assess improvement
in horses what is generally the only determinant of regenerative anaemia
macrocytosis
list some blood smear morphologic changes seem with regenerative anaemia
1) polychromasia
2) macrocytosis, anisocytosis, hypochromasia
3) increased Howell-Jolly bodies
4) increased nRBCs
5) basophilic stippling
what are the two ways in which reticulocyte counts are performed
1) manual reticulocyte count - use new methylene blue stain, count number reticulocytes per 1000 red cells
2) analyser reticulocyte count - use fluorescence stains - two forms in cats
1. aggregate reticulocytes
2. punctate reticulocytes
what are the two types of reticulocytes found in cats and what do they tell you are they found in health
Aggregate reticulocytes = polychromatophils
- Released in low numbers in normal dogs (1%) and cats (0.4%)
- If count generally just count this type
Punctate reticulocytes
- More mature form with only a few fine reticulin granules.
- Long maturation time in cats ( >2 weeks) so up to 10% punctate reticulocytes are seen in health
- Doesn’t tell you what bone marrow does today
what are the two ways in assessing the degree of regeneration and describe
1) absolute reticulocyte count
- retic% x RBC count - amount of reticulocytes per L of blood, normal within 0-120x10^9/L
- above the reference if regenerative
2) corrected reticulocyte %
- CRP = Retic % x (patient Hct / average species Hct)
- Want higher counts with more severe regenerative anaemia
birds, dog and cat what is normal correct reticulocyte percentage
- healthy birds 4-5% reticulocytes
○ CRP >1% in dog = regenerative
○ CRP >0.4% in cat = regenerative
what are the 3 anaemia erthrocyte indices
1) MCV - mean corpuscular volume
2) MCHC = mean corpuscular hemoglobin concentration
3) RDW - red cell distrubution width
what does MCV measure and what is the word to describe increase or decrease, what if normal
- Average volume of erythrocytes
- Measured value
- Increase = macrocytic - immature cells that haven’t condensed
- Decrease = microcytic
- Can have normal with regenerative
what does MCHC measure and what called if increase or decrease
mean corpuscular haemoglobin concentration
- Hb per average erythocyte
- Increased = Not possible
○ Artefacts: haemolysis, lipaemia, Heinz bodies
- Decreased = hypochromic
what does RDW measure and what does increase or normal mean
- Measures the variation in cell size
- Increased RDW indicates anisocytosis – could reflect macrocytosis and/or microcytosis
- normal - isn’t enough variation in size to effect - could still be regenerative
What occurs in terms of response to acute haemorrhage in the per-acute, acute stage 1 and acute stage 11
Per-acute
- No change Hct or protein
Acute Stage I (within hours)
- Decreased Hct and protein - combination - haemorrhage
○ Fluid shift extravascular to intravascular space
○ Activation of RAAS - PCV drops so can then detect
No evidence regeneration (pre-regenerative - per-acute and acute stage)
Acute Stage II (within 3-5 days)
- EPO produced - marrow stimulation
- Evidence of regeneration in blood
- Hct and protein start to rise if haemorrhage is controlled
what is the response to actue haemolysis in stage 1 and stage 11
Stage I (within hours)
- Decreased Hct with normal protein -
- No evidence regeneration (pre-regenerative)
- +/- haemolysed plasma and haemoglobinuria (as filtered by the kidney)
Stage II (within 3-5 days)
- EPO produced - marrow stimulation - Evidence of regeneration in blood
- +/- haemolysed plasma and haemoglobinuria
- Often see hyperbilirubinaemia/jaundice
- Hct starts to rise if haemolysis controlled
What are the 6 main findings with haemolysis
1) Haemoglobinaemia and haemoglobinuria (intravascular)
2) hyperbilirubinaemia and bilirubinuria
3) Regenerative anaemia (unless peracute)
4) Spherocytosis (if immune mediated haemolysis)
5) Schistocytes and keratocytes (if microvascular fragmentation)
6) Normal protein (no plasma loss)
what are 6 main causes of haemolytic anaemia
1) immune mediated haemolytic anaemia
2) oxidative injury - paracetamol in cats
3) infections - clostridium
4) zinc, copper toxicosis
5) genetic disease - PFK deficiency in dogs
6) neoplasia
what are the 3 types of IMHA and causes and what animals common
1) primary IMHA - idiopathic autoimmune - dogs common
2) secondary IMHA - common cats
- drugs, vaccination, infection - feline leukaemia viral infection, mycoplasma haemofelis, neoplasia, SLE
3) Alloimmune (Ab against foreign erythrocyte antigen)
- neonatal isoerythrolysis (colostrum produced antibodies) or blood transfusion
What are some key features for diagnosis of IMHA
- spherocytosis
- auto-agglutination in saline positive agglutination
- coombs test - looks for agglutination using antibodies
- exclusion of other primary diseases - infection, neoplasia, drug therapy
non-regenerative anaemia (NRA) what have to be careful with
need to differentiate from pre-regenerative anaemia - persistence > 5-7 days
- horses also don’t produce reticulocytosis
what are the two mechanisms of NRA
1) Reduced erythropoiesis = not making enough erythrocytes
2) Defective erythropoiesis = making abnormal erythrocytes
What are 4 causes of reduced erythropoiesis
1) Anaemia of inflammatory or chronic disease - common for mild non-regenerative anaemia
2) Decreased EPO production - most common is kidney disease
3) Immune mediated destruction of precursors (bone marrow cells)
4) Marrow diseases
Infectious diseases
what is the mechanism behind anaemia of inflammatory disease/chronic disease and laboratory findings
non-regenerative anaemia Mechanisms - Inhibition of EPO action - Iron sequestration (Hepcidin mediated) store within macrophage - body response to bacteria - Decreased erythrocyte survival Laboratory findings - Normocytic normochromic - Mild to moderate anaemia (Hct 20-30%) - Decreased serum iron - Evidence of inflammation or chronic disease
what are the two causes of decreased EPO production
1) Chronic renal disease –decreased EPO production, reduced rbc lifespan, GIT bleeding and uraemia suppression of erythropoiesis
2) Endocrine disease – hypoadrenocorticism, hypoandrogenism, hypopituitarism (mechanisms not understood)
immune mediated destruction of precursors what occurs, and why
- Pure red cell aplasia – selective loss of erythroid precursors from bone marrow
- Much less common than regenerative IMHA
- Appears to be immune mediated based on response to corticosteroids and/or lymphocytotoxic drugs
List 5 marrow disease that cause anaemia
1) Myelophthisis – infiltration of marrow by neoplastic cells eg lymphoma
2) Myelofibrosis – fibrosis of the marrow
3) Myeloproliferative disease eg leukaemia, myelodysplastic syndrome
4) Marrow toxicity/damage eg bracken fern, drugs (phenylbutazone), chemotherapy, radiation
5) Aplastic anaemia (concurrent leukopenia and thrombocytopenia) - less white, red blood cells and platelets
What are 3 infectious causes of non-regenerative anaemia
1) FeLV – killing of erythroid stem cells and progenitor cells along with dyserythropoiesis (macrocytic anaemia) - vaccination programmes
2) Anaplasma infection
- Ehrlichia canis infects monocytes, causes pancytopenia - exotic to Australia
3) Parvovirus – killing of rapidly dividing cells (haematopoietic cells, lymphoid cells, intestinal crypt cells), causing pancytopenia
