Exam 1 Flashcards
Define hematology
The study of the structure and function of blood, blood forming organs, and their diseases
Microscopically identify elements of blood and blood forming tissues
Aqueous fraction - plasma
Acellular, water based
Plasma- uses anticoagulant
Serum- clotted plasma
Proteins in the plasma- albumin and globulins (ie. immunoglobulins, acute phase proteins, coagulation proteins, etc)
Electrolytes, nutrients, metabolic by-products, and signaling molecules are also found in plasma
Cellular fraction- RBC, leukocytes, and platelets
What is erythrocyte structure and function? What are species differences?
Fxn: oxygen delivery
In the millions per microliter
Structure- donut like with center divot (thinner in center); enucleated
Easiest to see in dig RBC
Goats have small RBC
Deer- sickle shaped RBC, artifact from blood reacting with oxygen
Alpaca and other camelids- elliptical
Non mammalians- nucleated RBC
What are leukocyte functions and kinetics
Fxn: protection from exogenous (eg. infectious organisms) and endogenous (eg. cancer) harmful agents
In the thousands per microliter
Kinetics of neutrophils
Large number of neutrophils often needed in a short time
Storage pool necessary
Small animals- large pool
Large animals- small pool
Multiple factors stimulate production (IL-3, GM-CSF, G-CSF)
Most factors are produced by the cells of immune system
Glucocorticoids induce release of storage pool neutrophils → higher neutrophilia is seen in small animals as opposed to large animals
Leukocyte morphology- granulocytes vs mononuclear
Granulocytes or PMNs (polymorphonuclears)- cytoplasm has granules, nuclei are segmented and produce lots of different shapes; terminology reflects color when stained
Neutrophils- granules stain neutral
Eosinophils- granules stain orange
Basophils- granules stain blue-purple
Mononuclear- nuclei are not polymorphic, they are round
Lymphocytes
Monocytes
What is platelet function and hemostasis
Fxn: blood coagulation
In the hundreds of thousands per microliter
What are the appropriate technique of evaluation of blood and the blood forming tissues
Technique- blood must be maintain a liquid → use of an anticoagulant
Two components of coagulation- calcium ions (cofactors of many coagulation enzymes) and thrombin (a key protease)
EDTA (ethylene diamine tetra acetic acid)- used as an anticoagulant most often for a CBC, hematological purposes. Binds calcium to make it unavailable for clotting
Citrate- used as an anticoagulant most often for coagulation studies. It is also used to collect blood for transfusion purposes. Binds calcium to make it unavailable for clotting
Heparin- inhibits coagulation ny activating antithrombin, which inhibits the action of thrombin
Occasionally used for both hematology and blood chemistry analyses. Useful in small animals because unlike EDTA, plasma could be analyzed biochemically after hematological analysis
Hematologic evaluation
Hemogram or CBC
Consists of erythrogram, leukogram, thrombogram, and miscellaneous (plasma) sections
Bone marrow examination
Immune evaluation- Coomb’s test
Blood typing and cross match
Clotting studies
Flow cytometry
Relies on light (laser) interacting with cell
Generates shape and size of cell
Scattering of laser reflects internal complexity
After, stain the cells to determine type of cell
Or Blood smear and manually count (hemocytometer)
Define Hematopoiesis
production of all blood elements (ie. RBCs, platelets, and all leukocytes
Define myelopoiesis. What falls under this category
Myelopoiesis- production of non lymphoid bone marrow or bone marrow derived cells
Erythropoiesis- erythrocyte production
Granulopoiesis- neutrophil, eosinophil, and basophil production
Thrombopoiesis or megakaryocytopoiesis- platelet production
Define lymphopoiesis
lymphocyte production
What is the lifespan of different blood cells
Neutrophils- 10 hour life span
Platelets- 10 day life span
RBCs- 100 day life span
In mammals, RBC life span is correlated with size
Lymphocytes- May live for many years
Where are blood cells made in mammals? How does this change with age? How does this change when stressed?
Embryo- yolk sac (mesenchymal blood islands), liver and spleen
Fetus- liver, spleen, bone marrow (kidney, lymph nodes)
After birth- bone marrow
Young age- long and flat bones
Adults- flat bones and ends of long bones
Growing animals expand blood cell population. Adult maintain blood cell population
During stress, sites of fetal hematopoiesis can reactivate → extramedullary hematopoiesis
Where are blood cells made comparatively?
mammals - bone marrow
Occurs extravascular
Once matured, go into sinus → blood vessel → go into circulation
Have megakaryocyte- big nucleated cells make platelets
Types of cells are intermixed together
Birds- bone marrow
Occurs extravascular but erythropoiesis and thrombopoiesis occurs inside of the sinuses
No megakaryocyte- have other cells but not morphologically different than their other cells → can’t see on slide
Types of cells are clustered together (ie. granulopoiesis in extravascular space, erythropoiesis within the sinusoid lumen)
Reptiles- bone marrow and spleen
Amphibians- spleen, kidney, and liver
Fish- kidney, spleen, and liver
What factors stimulate blood cell production?
Humoral growth factors
Regulate proliferation and differentiation of bone marrow cells
Factors often act together in order to regulate production of a particular cell line
Some factors, may stimulate the production of a specific cell type, but inhibit the production of a different cell type
Liver- constitutive and inducible thrombopoietin
Kidney- inducible erythropoietin –> If there is renal failure, decreased erythropoietin and anemia is seen
What is a hematopoietic microenvironment “niche”?
Hematopoiesis is regulated by a unique combination of structural, biochemical, nutritional, and cellular influences that develop or exist in bone marrow
Stromal cells, macrophages, endothelial cells, neurons, and the developing cells produce growth factors that influence that proliferation, commitment, differentiation, and maturation of developing cells
In addition, the matrix traps humoral growth factors and nutrients in the local area
What are proliferative, maturative, and storage bone marrow pools?
Conceptual pools
Progenitor compartment small cells- immature cell type; can’t tell which one is which
Precursor Compartment- recognizable cells (can see fate of cells)
Proliferative- cells are dividing and differentiating
Maturative pool- lost proliferative function, just maturing, differentiating
Storage- waiting in bone marrow, waiting to be pulled
What are changes as blood cells mature?
Cell size and nucleus size decrease (except megakaryocytic lineage)
Nucleus to cytoplasm ratio (N:C) decreases
Nucleoli disappear
Chromatin condenses
Basophilia of the cytoplasm decreases as RNA decreases
Specific cytoplasmic contents accumulate (ie. granules)
What are features of erythropoietic precursor cells
Rubriblasts, prorubricyte, basophilic rubricyte- very blue cytoplasm, lots of rough ER to make protein
Polychromatic rubricyte- cytoplasm gets paler due to filling with hemoglobin (red color) while ribosomes still present (blue color)
Metarubricyte- gray/blue to red cytoplasm as even more hemoglobin, less RNA
Reticulocyte- no nucleus, pale blue-grey cytoplasm; residual RNA stains with new methylene blue
Same as polychromatic erythrocyte
How are erythropoietic precursor cells characterized in the compartments in bone marrow
proliferative pool- rubriblasts, prorubricyte, basophilic rubricyte
maturative pool- polychromatophilic rubricyte, metarubricyte, reticulocyte
storage pool- no BM storage
What are features of neutrophil precursor cells
Myeloblast- looks like rubriblasts, big round nucleus, euchromatin, nucleolus, small cytoplasm, blue cytoplasm
Proliferative pool
Progranulocyte- primary granules common
Myelocyte- primary granules go away and show up in this stage
Metamyelocyte
Band neutrophil
Mature neutrophil- nucleus fully segmented
Would be in maturation pool
What are some factors that stimulate neutrophilic production
G-CSF
Acts on progenitors, mitotic precursors
Increase number of neutrophils produced
Shortens production and maturation
Neutrophils ready sooner
Increases release of neutrophils from bone marrow
Gets more out of the bone marrow
Enhanced tissue emigration and functional capabilities
Used therapeutically
IL-5: stimulates eosinophil production
What would glucocorticoids do in regards with neutrophils?
Glucocorticoids induce release of storage pool neutrophils → higher neutrophilia is seen in small animals as opposed to large animals
What are some facts about monocytopoiesis? Like about storage pools? Distinguishable stages?
CFU-GM: shared progenitor of neutrophils and monocytes
Cell lines diverge after CFU-GM
CFU-GM → monoblasts → promonocytes → monocytes
Monoblasts and promonocytes are difficult to distinguish from myeloblasts and promyelocytes
Monocytes do not stay in bone marrow: no storage pool
Early stages of monocytopoiesis cannot be confidently recognized morphologically
Monocytes become macrophages/histiocytes after leaving blood
Macrophages undergo many changes in tissue
What are platelets? How long do they live?
Platelets are cytoplasmic fragments from megakaryocytes
Highly complex cytoplasmic contents
Contain granules important in hemostasis
Can change shape
Live in circulation for about 6- 10 days
How is thrombopoiesis different than other blood cell productions and maturation?
Different because they get larger as nucleated precursors mature in the marrow
Mega- basophilic cytoplasm and 1-2 distinct nuclei
Endocytotic division
Pro- abundant RNA in cytoplasm → blue color cytoplasm
Continue endocytotic division
Cytoplasm increases in volume
Production of cytoplasmic contents occurs
Megakaryocytes (biggest) → break up into platelets
How is platelet production controlled?
Constitutive productive of TPO
Liver (and kidney)
Platelets bind TPO → inactivates
If normal platelet supports TPO binding → steady thrombopoiesis
Thrombocytopenia → more free TPO
Increased megakaryopoiesis
Not as many platelets to bind TPO
Increased TPO ⇒ increased platelet production in bone marrow
Thrombocytosis
Decreased megakaryopoiesis
Does does platelet production differ among different species?
Birds, reptiles, amphibians, and fish have nucleated platelets
Thrombocytes- small cells with clear cytoplasm and small nuclei
Have few small granules in their cytoplasm
Produced in bone marrow vessel sinusoids
How is transfer of thrombocytes from marrow to blood in birds?
In birds, erythrocytes and thrombocytes develop in marrow blind sac sinusoids
These cells do not have to move across the vessel walls to enter the blood
Thrombocytes simply leave the sinusoids and enter the blood
What are common cellular elements of normal bone marrow?
Bone marrow is the primary hematopoietic organ in adults
2-3% of body weight
In young animals, the marrow of all bones is red due to hemoglobin
Active hematopoiesis
In adult animals, the mid-shaft marrow of long bones is yellow due to fat replacement of hematopoietic cells
Nutrient arteriole- surrounded by hematopoietic cells
Endothelial cells- interconnected cells lining the blood vessels
Granulocyte progeny
Stromal or reticular cell- produce hematopoietic short range regulatory molecules
Macrophage- engulf nuclei that extrude from erythroblasts when they turn into reticulocytes
Megakaryocyte- lies against veins and branches discharge platelets into vein
Send long pseudopodia into the blood
Cytoplasm of pseudopod fragments into platelets
Megakaryocytes shed platelets directly into the blood
What are the overarching functions of the immune system in health and disease
Protect the host from infections
Prevent invasion by pathogens
removal/inactivation of pathogens after infection
Protection from re-infection
Supports organ system health
Regulation of microbiota
“Housekeeping” functions such as removal of dead and dying cells
Tissue repair/remodeling
What organs and cellular components are part of the immune system
Primary lymphoid tissues
Bone marrow- leukocyte development (hematopoiesis)
Fetal liver- development of leukocyte prior to birth
Thymus- generation of “T” lymphocytes
Secondary lymphoid tissues- localized responses
Spleen- filters blood
White pulp- filtering and removal of non-self components
Red pulp- filtering and removal of dysfunctional erythrocytes
Lymph nodes- filters lymphatics
Tonsils, peyer’s patches- filters antigens on surface of mucosal tissues of the respiratory (tonsils) and gastrointestinal (peyer’s patches) tract
Appendix- species specific functions
Tertiary lymphoid tissues- less developed than secondary but under right circumstances, can expand
Lymphocytic aggregates- develop after strong and/or chronic exposure to microbes (bacteria/viruses/parasites) or chronic inflammation
What are the fundamental differences between the innate and adaptive immune systems
Innate cell receptors- invariant in recognizing specific motifs or patterns and structures (Pathogen Associated Molecular Patterns and Danger Associated Molecular Patterns)
TLR4:LPS
Adaptive cells (lymphocytes)- active following binding to antigens
T and B lymphocytes recognize a specific stretch of primary amino acid sequences → three dimensional structure “conformation” of an antigen
These recognition motives on antigens are called epitopes
T cell- linear
B cell- any conformation
Difference is in the types of receptors they have
Define CD markers
agreed upon naming system for proteins associated with cells, especially on cell surface
CD followed by a number referring to a unique structure/molecules on cells
Define Antigen
antibody generation
Molecules that bind to specific receptors
Define antigen receptors
receptor on lymphocytes that binds to antigens
What are the principles of the immune cell activation
Tissue resident innate immune cells will secrete chemokines and cytokines that activate endothelial cells to express selectin ligands
Leukocyte express selectins and activation changes expression of chemokine receptors. Endothelial cells express selectin ligands after injury. Leukocytes start slowing down “rolling”
Slowing down of cells allows them to bind to selectin ligands and chemokines, which will lead to activation of integrins
Activated integrins bind to endothelial cells, which causes firm adhesion of the cell
The cell will transmigrate from blood into tissues following a chemokine gradient
How are leukocyte migration pattern connected to their function and activation state
In health, they continuously move through arterial and venous blood and in and out of secondary organs → into non-lymphoid tissues and can return into circulation
If they get a signal (chemokine, cytokine), leukocytes are instructed to leave the blood and either get sequestered in secondary lymphoid tissues and/or enter a tissue/organ
Migrated to tissue- activated
Describe the general structure of hemoglobin and how binding to oxygen is regulated
Four peptide chains together → 2 alpha and 2 beta chains
Each chain has a heme → each each has iron
Heme is a porphyrin ring, with iron in the middle
Iron has two states
Ferrous- 2+ “for us” → used for breathing
Ferric- 3+ “icky” → oxidized and can’t be used for oxygenation
Regulation→ affinity for oxygen is adjustable to tissue environment (Bohr environment)
Lower pH and lower O2 content (eg. in actively metabolizing tissues) facilitates unloading of oxygen (lower affinity)
Decreased pH
Increased 2-3 DPG
Increased CO2
Increased temperature
Shift to the right
Higher pH and higher O2 content (eg. in the lungs) facilitates loading of oxygen (higher affinity)
Increased pH
Decreased 2-3 DPG
Decreased CO2
Decreased temperature
Shift to the left
Name the main metabolic pathways in the red cell and their primary function
Methemoglobin Reductase Pathway- ensuring Fe stays in ferrous state and not ferric state
Ferric iron = methemoglobin → lose all oxygen carrying capacity
NADH takes the charge from ferric → becomes NAD+ and ferrous
Always on and can be overwhelmed
Rapoport-Luebering pathway- 2,3 DPG synthesis → regulates hemoglobin oxygen affinity
Define the major steps in hemoglobin synthesis; give an example of a disease that interferes with synthesis
Highly complex, involving organic compounds
Some steps happen in mitochondria and some in cytoplasm
Abnormalities in heme synthesis due to
Porphyrias (inherited enzymes defects in porphyrin synthesis)- very rare; lowers RBC and oxygen carrying capacity
Dyserythropoiesis (acquired defects)- due to toxin or tumor
Heme synthetase and Fe2+ - sticking heme onto RBC
Dyserythropoiesis, specifically lead toxicity leads to this shutting down
ALA dehydratase- cleaves off water from components
Lead toxicity deactivates this
Outline the basic steps and key molecules involved in iron absorption, utilization, and recycling
Iron absorption through diet and intestinal absorption
Iron and heme absorbed through enterocyte → broken down into ferrous iron → have three final outcomes
Ferritin: iron storage protein in macrophages (short term)
Hemosiderin not really accessible but also in macrophages
Ferroportin: iron “portal” protein, regulated by hepcidin (hormone)
Master regulator of iron across body
Increased hepcidin ⇒ decreased ferroportin ⇒ less iron transported in
Decreased hepcidin ⇒ increased ferroportin ⇒ more iron transported in
Synthesized in the liver
Adjusts to changes in body iron stores
Adjusts to changes in erythrocytes (hemoglobin synthesis)
Released in inflammation
Blocks release of iron absorption in the intestine and blocks release of iron from macrophages to developing erythroid cells
Transferrin: iron transport protein in serum
Can bring it to a macrophage to be stored
Utilization in erythropoiesis
Iron travels in plasma and binds to bone marrow macrophage → binds to transferrin receptor → internalizes Fe
Can be stored in ferritin (short term) and hemosiderin (long term) storage
Can be transferred through macrophage and ferroportin protein (regulated by hepcidin) to erythroid precursor cells
Iron recycling from senescent red cells
Circulating RBCs in peripheral blood → erythrophagocytosis of senescent (old) RBCs → in macrophage → heme is broken down → iron is taken from it and can go in the three pathways
What is “RBC mass” and how is it measured
HCT= hematocrit (%)
Percent blood occupied by RBC → extrapolated
Spun microhematocrit (PCV)
Calculated HCT= RBC count x MCV (size)
Most representative of mass
RBC= red cell count (number of RBCs/microliter)
Not much emphasis as it could be misleading → having tiny or big RBC can lead to inaccurate count
HGB= hemoglobin concentration (g/dl)
Used more in human medicine
Describe the main components of the red cell membrane and their functional purpose
RBCs change shape as travel capillaries → RBC membrane must be deformable
ATP provides energy for membrane contractile proteins → change the shape RBC and return its normal shape when RBC reenters larger vessels
Cytoskeleton (structural proteins)- in cell and anchored to the membrane
Help determine and maintain RBC shape
Viscoelastic properties
Delimit deformability
Cross linked or damage = loses elasticity
Lipid bilayer- provides anchor point
Permeability barrier
In equilibrium with plasma lipids → plasma proteins can alter RBC membrane → alters function and flexibility
Noncompressible
Outer membrane- a lot of CHO → makes it tough so it can take damage
Too tough or too weak → lysis
Inner membrane- ion channels → move ions so that internal solutes = external solutes for osmotic pressure
Membrane components (horizontal and vertical)
Spectrin- spider web; really strong; can move all around; allows them to bend
Actin- facilitates bending (flexing) → proactive movement
Vertical- points of anchor help vertical interactions without lysing
Explain the major causes and implications of abnormalities involving the red cell membranes
Embden-meyerhof pathway
Relies on ATP production for membrane shape, cation pump, and ionic gradient
Maintains cell function and size
Maintain osmotic balances
Abnormalities- can lead to water going into cell → lysis or water going out of cell
Membrane abnormalities
Structural abnormalities (in lipids or proteins)
Metabolic abnormalities (often involve ATP, Ca2+)
These can lead to
Decreased deformability → lysis
Shape changes (poikilocytosis)- more prone to damage or not bending
Premature destruction (hemolysis)
What is a poikilocyte?
abnormally shaped red cell
What is an echinocytes (crenation)? What is the mechanism of formation?
has pointy edges, smaller, evenly spaced and shaped
Normal or artifact: Drying artifact in smear preparation; prolonged storage in EDTA
Pathologic: electrolyte abnormalities, uremia, rattlesnake envenomation
What is an acanthocyte? What is the mechanism of formation?
big, rounded projections, larger and more irregular compared to echinocytes
Normal: pigs, calves, rabbits
Pathologic: hepatic disease, lipid abnormalities, red cell fragmentation, neoplasia → incorporations of too little or too much CHO into the outer leaflet of the lipid bilayer causes irregular membrane protrusions
What are target cells? What is the mechanism of formation?
lose biconcase nature
Normal or artifact: drying artifact in smear preparation
Pathologic: anemia (nonspecific), iron deficiency, hepatobiliary disease
What are schistocytes? What is the mechanism of formation?
tiny fragments of RBC torn apart and membrane reanneals
Normal: none
Pathologic: red cell fragmentation → seen in small or large clots → fibrin is really tough → results in cleavage
What are keratocytes? What is the mechanism of formation?
Normal: none
Pathologic: red cell fragmentation → membrane blisters and it goes outwards
Common in bad trauma → results in a lot of blood clots
What are spherocytes? What is the mechanism of formation?
very rounded than normal; lose biconcave nature
Normal: none (rabbits may have a few normally)
Pathologic: immune-mediated hemolytic anemia (when spherocytes are the only poikilocyte)
Agglutination- crosslinking of antibodies on RBC surface and causes them to clump together → with spherocytes, it is a hallmark of IMHA
Pathologic: RBC fragmentation (when few spherocytes and schistocytes and acanthocytes, etc) → part of RBC membrane is removed by macrophage and remaining membrane reseals around the cytosol
What are Heinz bodies? What is the mechanism of formation?
Oxidation of globin chains, which clump and bind to the inner red cell membrane, protruding from the surface
Cause- oxidant drugs, plants, chemicals
Feline HGb is oxidant-sensitive
High number of SH groups
Up to 5% of RBCs may contain Heinz bodies (more with some fish diets)
Staining- hard to detect with eyes but when stained with methylene blue → you can see
What are eccentrocytes? What is the mechanism of formation?
less common than Heinz
Internal structure membrane oxidizes → stick together and squishes the cell → hemoglobin is pushed onto one sude
Normal: none
Pathologic: oxidative damage (+// Heinz bodies, eg. onion induced hemolysis)
Diagram the pathway of red cell and hemoglobin degradation
Metabolic functions fails, ATP is depleted
Reducing power fails, gradual oxidation of hemoglobin
“Senescence” antibodies bind to altered membrane proteins
Phagocytosed by splenic macrophages
RBC enters macrophage → globin is broken down into AAs and heme is broken down into iron and other elements → bilirubin (chemically inert)→ bili put on mac surface → albumin takes the bili → takes to hepatocyte (liver) → liver sticks sugar on it → soluble in water and gets defecated in health
In disease, hyperbili → bilirubinemia → get rid of it through GI or kidney → bili in urine (biliuria)
Describe where plasma proteins are synthesized
Albumin- maintains oncotic pressure; also a carrier protein
Synthesized by hepatocytes (liver)
Highest concentration of any single protein in plasma
~65 kDa (small)
Globulins
Immunoglobulins (gamma)- antibodies produced by adaptive immune cells
Synthesized by plasma cells
Account for most of the globulins in plasma
150-970 kDa (big)
Other globulins (alpha, beta)- roles in innate inflammatory response
Synthesized by hepatocytes (liver)
Acute phase proteins; transport proteins; complement; clotting proteins; lipoproteins
Hepcidin falls under this category
Variable kDa (small)
Explain the difference between plasma and serum. How do we measure proteins in them?
Plasma- includes all proteins, including fibrinogen and clotting factors
Purple top tube (CBC)- EDTA anticoagulant
Proteins levels always higher compared to serum
Plasma protein, plasma fibrinogen, and protein:fibrinogen ratio measured
Refractometry- refractive index correlates with solute concentration
Accurate to +/- 0.1 g/dl
High concentrations of glucose, sodium, or urea can falsely increase TPP
Hemolysis and lipemia can interfere with reading
Serum- fibrinogen and clotting factors are absent, consumed in the clot
Red top tube (chem panel)- no anticoagulant
Total protein- biuret method
Highly specific and sensitive
Albumin- bromocresol green method
Species differences in dye binding (doesn’t work in birds)
Bilirubin and some drugs interfere with binding
globulin= (total protein - albumin)
a/g ratio calculated to detect disproportionate changes
Describe the main pathophysiologic mechanisms for hyperalbuminemia
dehydration (relative)
Globulins also increase proportionately
The liver never synthesizes too much albumin
Describe the main pathophysiologic mechanisms for hyperglobulinemia
Increased production of gamma globulins (hypergammaglobulinemia)
Chronic inflammation (commonly seen)
Increased immunoglobulin (antibody) production by plasma cells due to chronic antigenic stimulation
Albumin WRR
Polyclonal gammopathy → broad based gamma peak
Lymphoid neoplasia
Abnormal immunoglobulin (paraprotein) produced by neoplastic plasma cells or B lymphocytes
Low albumin occasionally
Monoclonal gammopathy → narrow based gamma peak
Describe the main pathophysiologic mechanisms for atypical gammopathies
Occasionally, infections can cause a monoclonal spike (+/- polyclonal)
Canine ehrlichiosis - most common
Leishmaniasis
Rarely other lymphoplasmacytic inflammatory lesions
Describe the main pathophysiologic mechanisms for hyperproteinemia
can result from increased albumin, increased globulins, or both
Hyperalbuminemia with normal or increased globulins → dehydration
Hyperglobulinemia with normal or decreased albumin → chronic inflammatory disease* or lymphoid neoplasia
Describe the main pathophysiologic mechanisms for increased production of alpha and beta globulins
Acute phase response
Cytokine-mediated production of “Acute phase proteins” - mostly in the liver
Most of these proteins are in very low concentrations in plasma, so increases do not usually affect total protein or globulin concentrations
Also increases fibrinogen and decreases albumin (minor)
Hyperfibrinogenemia
Fibrinogen is the most abundant acute phase protein
Increases in fibrinogen can increase the total plasma protein concentration
Acute (and chronic) inflammation
Large animals
Chronic inflammation
Small animals, birds
Prot:Fib ratio
Proportionate increase in dehydration (more than or equal to 15)
Disproportionate increase in fibrinogen is inflammation (ratio less than 15)
Remember to convert mg → g (divide by 1000)
Describe the main pathophysiologic mechanisms for hypoalbuminemia
Decreased synthesis
Hepatic insufficiency
Acute phase response
Compensatory response to marked hyperglobulinemia
Increased loss
Renal loss (glomerular) → urine
Gastrointestinal loss (diarrhea, malabsorption)
Blood loss, exudates, vasculitis
Decreased intake and increased utilization/catabolism (malnutrition/cachexia)
Describe the main pathophysiologic mechanisms for hypoglobulinemia
Decreased synthesis
Immunodeficiencies (hypogammaglobulinemia)
Hepatic insufficiency (decreased alpha, beta globulins)
Increased loss
Renal loss (small globulins are lost in severe tubular disease)
Gastrointestinal loss (diarrhea, malabsorption)
Blood loss, exudates
Decreased intake (failure of passive transfer)
Describe the main pathophysiologic mechanisms for hypoproteinemia
Can result from hypoalbuminemia, hypoglobulinemia, or both
Panhypoproteinemia (hypoalbuminemia + hypoglobulinemia) → liver failure or loss
Hypoalbuminemia with normal or increased globulins → primarily albumin production issue
Hypoglobulinemia with normal or increased albumin → primarily globulin production issue
What is neutrophil function?
primary first line defense versus bacterial infections- acute inflammation
What is neutrophil structure?
Mature neutrophils have multiple nuclear lobes separated by constrictions (filaments)
Contain cytoplasmic lysosomal granules that take up a little stain (with routine stains)
Primary or azurophilic granules
Larger and more electron dense than secondary granules
Stain red/purple with Romanowsky stains but don’t stain and aren’t visible after the promyelocyte stage in many species
Contents include proteases, acid hydrolases, peroxidase, lysozyme, microbicidal cationic proteins, esterases, glycosaminoglycans
The microbicidal properties of neutrophils are contained primarily in the lysosomal granules
Degranulation results in release of enzymes and proteins
Oxygen dependent or independent
Secondary or specific granules
Usually not visible (in neutrophils) with Romanowsky stains
Contents include lysozyme, lactoferrin, collagenase, plasminogen activator, phospholipase A
What is eosinophil and basophil function?
important in protection against helminth infections and participate in allergic reactions
What is monocyte function?
become macrophages (in tissue); key players in phagocytosis
Antigen processing and presentation
Production of inflammatory mediators and cytokines
What is lymphocyte function?
antibody and cytokine production; mediators in destruction of microorganisms and tumor cells
distinguish between self and non self
Responsible for memory
Humoral and CMI
Are there species differences when it comes to blood cells?
In some animals, heterophils instead of neutrophils
Heterophils in rabbits, guinea pigs, birds, and reptiles
What are leukocytes
nucleated cell that travels through the blood to get to the tissues, where it functions (literally, means “white cell”, based on its unstained appearance)
