S
Clinical Pathology
subspecialty of pathology that uses primairly antemortem lab tests for diagnosis + management of disease
- CBC (whole blood)
- clinical chemistry (serum or plasma)
- UA
- coagulation testing
- endocrine testing
- fluid analysis
- cytology
- more
Hematology
study of physiology of blood
Blood = erythrocytes (RBCs) + leukocytes (WBCs) + platelets + plasma
Blood = 55% plasma + 45% cells (mostly erythrocytes)
Erythron + Function
circulating erythrocytes + erythopoietic cells in bone marrow
main function is to transport oxygen by using Hb
Normal Mammal RBC Shape
biconcave disc (discocyte)
- shape allows substantial deformability while travelin vessels
- central pallor where cell is thinnest
pallor most prominent in dogs
smaller RBCs have less prominent pallor
Normal avian/reptile/amphibian RBC shape:
oval/elliptical nucleated erythrocytes
Hemoglobin (Hgb)
tetrameric metalloprotein consisting of 4 heme + 4 globin mol.
- each globin contains heme moiety
- each moeity contains iron atom in 2+ valence state
oxygen binds to Fe2+ allowing 1 Hgb to transport 4 O2 molecules
- each RBC contains millions of Hgb
acts as pH buffer + carries some CO2 back to lungs from tissue
O2 Affinity for Hgb influenced by:
- body temp
- blood pH + CO2
- RBC conc.
Methemoglobin
if Fe2+ (ferrous) is oxidized to Fe3+ (ferric) 🡒
- Hb 🡒 methemoglobin
- O2 carrying capacity severely reduced/negated
Results in:
- cyanosis
- methemoglobinemia
secondary to certain toxicities + rare genetic anomalies
classic case = acetominophen toxicity in cats
Erythrocyte Metabolism
Mature mammalian RBCs lack:
- nuclei
- mitochondria
therefore mature RBC produces ATP + NADH thru aneorobic glycolysis
- glucose major energy source
Blood Cell Production
Hematopoiesis v Extramedullary v Erythropoiesis
Hematopoiesis:
- production of RBCs + WBCs + platelets within bone marrow
Extramedullary Hematopoiesis:
- production of blood cells outside of bone marrow
- spleen, liver, adrenals, lymph nodes, etc
Erythropoiesis:
- production of erythrocytes
Erythropoiesis
erythroid precursors lineage:
- rubriblast 🡒 prorubricyte 🡒 rubricyte 🡒 metarubricyte 🡒 reticulocyte 🡒 mature erythrocite
rubriblast:
- 1st vissually discernable precursor
pluripotential + multipotential stem cells:
- self-renewing or differentiate into progenitor cells
Progenitor Cells:
- maintly differentiate into precursor cells
approx. 5 days from progenitor cell stimulation to release of reticulocytes into peripheral blood
differentiation controlled by many factors such as EPO, etc.
from rubriblasts, 3-5 divisions result in 8-32 differentiated cells
Regulation of Erythropoiesis
Erythropoietin (EPO)
- key regulator
- most produced by kidney + some by liver
- blocks apoptosis of certain precursors
- 🡑 Hgb synthesis
Others:
- cytokines
- hormones
Regenerative Response
- Bone marrow response to correct 🡓 in erythrocyte mass
- potential for shortened time to maturation (~3-5 days)
presence reticulocytes in circulation
- not expected in horses
- mild/absent in ruminants
Rate of Erythropoiesis
- normal = steady to match removal of aged RBCs
- anemic = abnormal 🡓 in RBCs
in response to some types of anemia, systemic mechanisms upregulate erythropoiesis
- primarily, anemoa d/t blood loss or erythrocyte destruction
Clinical implications of RBC lifespan
- often related to presence of polychromasia/reticulocytosis in health
- can contribute to development of anemia in disease
Removal of Senescent RBCs
MAJOR route of removal:
- Extravascular hemolysis = phagocytosis by macrophages within spleen (MPS)
MINOR route of removal:
- Intravascular hemolysis = spontaneous rupture of RBCs while in circulation
- free Hgb released into plasma
MPS = mononuclear phagocytic system
