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163 Cards in this Set
- Front
- Back
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Explain why RBCs rely on glycolysis for energy production
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Glycolysis generates ATP as energy source and NADH as reducing agent in MetHg reductase pathway
because they are anucleate and have no organelles so no protein synthesis or oxidative phosphorylation Still metabolically active for Active transport Maintain shape, deformability *Minimize oxidative damage* - MetHb reductase and Pentose Shunt |
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Define hematopoiesis
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The formation, proliferation, and maturation of blood cells
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define leukopoiesis
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The formation, proliferation, and maturation of leukocytes
Includes granulopoiesis, lymphopoiesis, and myelopoiesis |
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define erythropoiesis
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The formation, proliferation, and maturation of erythrocytes
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define myelopoiesis
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The formation, proliferation, and maturation of nonlymphoid leukocytes
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Platelet production consists of ________ & ______
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megakaryopoiesis and thrombopoiesis
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The formation of platelets from megakaryocytes
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thrombopoiesis
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Erythron
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All erythroid cells in an animal (includes precursors)
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Leukon
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All leukocytes in an animal (includes precursors)
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Thrombon
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All megakaryocytes and platelets in an animal (includes precursors)
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Hematopoiesis occurs primarily where
Where else can it occur? |
In the bone marrow
Spleen, liver, kidney, and lymph nodes |
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______ refers to hematopoiesis that occurs in the spleen (or liver)
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Extramedullary hematopoiesis
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_______ are self-renewing cells that are common ancestors of all blood cells
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hematopoietic stem cells
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The main hematopoietic lineages in the bone marrow are _______
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Erythroid, myeloid (nonlymphoid leukocytes, mainly neutrophils), and megakaryocytic
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Where to T lymphocytes derive from
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Bone marrow stem cells
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The hematopoietic system is under _____ control
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local and systemic
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The marrow cavity is interlaced with venous sinuses composed of a luminal layer of ____ and an abluminal layer of _______
Where does hematopoiesis take place |
Luminal layer of specialized endothelial cells
Abluminal layer of specialized fibroblasts known as adventitial reticular cells Between these venous sinuses |
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What lines the venous sinuses of the bone marrow creating a barrier and regulating the traffic of cells and other substances b/w the intravascular and extravascular space
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Sinusoidal endothelial cells along with their basement membrane
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______ forms a scaffolding which supports the hematopoietic cells of the bone marrow
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adventitial reticular cells
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_____ are a major component of marrow tissue with increases in amount with age
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fat cells
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_______ provides structural support to the marrow via remodeling bone within the marrow space & likely contribute to regulation of hematopoietic stem cell proliferation and trafficking
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Osteoblasts, osteoclasts, and elongated flat cells
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_____ provide structural & biochemical support to the marrow to support the hematopoietic process
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Specialized stromal cells (presumably of fibroblast origin)
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What are the different stimuli that drive proliferation and maturation of the 3 main cell lineages of hematopoiesis
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Erythropoiesis
-Hypoxia detected by JG cells which produced EPO Granulopoiesis -Inflammatory cytokines (IL-1, IL-6, and TNF-alpha) Thrombopoiesis/ Megakaryopoiesis -Thrombocytopenia results in increased plasma thrombopoietin levels |
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hypoxia has what effect on hematopoiesis
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increases erythropoiesis
JG cells produce EPO |
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IL-6 has what effect on hematopoiesis
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increases granulopoiesis
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increased plasma thrombopoietin levels has what effect on hematpoiesis
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increases thrombopoiesis
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Hematopoiesis is subject to ______ kinetics (in health)
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steady state kinetics
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Give the general maturation times and life spans for neutrophils, platelets, RBC, lymphocytes (days/ weeks/ months/ years)
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Neutrophils
-Maturation: 7 days -Survival: hrs Platelets -Maturation: 2-10 days -Survival: 5-10 days RBC -Maturation: 5 days -Survival: 100 days Lymphocytes -Maturation: 7 days -Survival: years (for some) |
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If a virus wiped out all of the early precursors, what cell lineage be depressed first on blood work
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Neutrophils
b/c survival is only hours |
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What is the dominant regulator of erythropoiesis
What is it and what effect does it have |
Erythropoietin
A glycoprotein synthesized by renal juxtaglomerular interstitial cells which have an oxygen-sensitive hydroxylase It promotes prolifieration and inhibits apoptosis of developing erythroid cells Normally takes 5 days for a rubriblast to develop into a mature erythrocyte in circulation |
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What effect does hypoxia have on EPO production
How? What happens under normal conditions? |
Up regulates it
Normal conditions -Transcription factor (hypoxia inducible factor 1alpha) is hydroxylated which allows it to bind to a protein called von Hippel-Lindau protein which targets the HIF-1a molecule for degredation In low oxygen tension (hypoxia) -The hydroxylase is inactive so HIF-1a isn’t hydroxylated avoiding subsequent binding to VHL and degredation -This promotes EPO gene expression |
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Granulopoiesis is regulated by what
Where does it come from Normal maturation time |
Many molecules including colony stimulating factors and interleukins
G-CSF is the primary regulator of neutropoiesis - Produced by endothelial cells, fibroblasts, and macrophages in many tissues - Production induced by inflammatory cytokines (IL-1, IL-6, and TNF-a) - Promotes neutrophil production by increasing number of cell divisions and shortening the maturation time Normal transit time from a myeloblast to release of a mature granulocyte into circulation is 7 days. |
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How are platelets formed
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By fragmentation of cytoplasm from megakaryocytes
Regulated by thrombopoietin - Synthesized in the liver (small amts made in kidney and skeletal muscle) - When platelet mass decreased, less TPO bound to platelet receptors and the increased free TPO stimulates thrombopoiesis Stromal cells in bone marrow increase production of TPO in states of severe thrombocytopenia Hepatic expression of TPO can be increased by inflammatory mediators such as IL-6 Increases rate of formation/ release of platelets and increases mass |
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_______ is the primary regulator of neutropoiesis
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granulocyte colony stimulating factor
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define plasma
how do you collect it |
the fluid (acellular) component of circulating blood
it is harvested after centrifugation of an anticoagulated blood sample |
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define serum
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the fluid component of blood that is harvested after centrifugation of coagulated blood sampel
the same as plasma except that it lacks most coagulation proteins the major protein that is absent in serum is FIBRINOGEN |
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how are plasma and serum different
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plasma is collected from anticoagulated blood
- contains fibrinogen serum is from coagulated blood - lacks fibrinogen |
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_____ is the major protein which differentiates plasma from serum
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fibrinogen
- present in plasma (anticoagulated) - not present in serum (coagulated) |
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what are the fxns of plasma proteins
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enzymes
- plasminogen antibodies - IgM, IgG, IgA inflamatory mediators - complement - C reactive protein coagulation factors - thrombin - factor x hormones - glucagon - insulin - growth hormone transport substances - transferrin - lipoproteins nutritive - amino acids |
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______ is the principal force opposing the exit of fluid from the vascular system
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colloidal osmotic pressure
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decreased ______ results in edema
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colloidal oncotic pressure
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decreased _____ causes ascites
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colloidal osmotic pressure
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decreased ____ causes hydrothorax
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colloidal osmotic pressure
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decreased _____ causes increased total body water
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colloidal osmotic pressure
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_____ is the contribution to effective osmolality from macromolecules (mainly albumin)
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colloidal osmotic pressure
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changes in _____ cause sshifts between ECF and ICF
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extracellular (serum) osmolality
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extracellular (serum) osmolality
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the number of solute particles per unit weight of serum
electrolytes and small molecules *such as glucose and urea* are the major contributors to the osmolality of serum |
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osmolality vs COP
which has proteins as a major contributor which has electrolytes as a major contributor |
COP
extracellular (serum) osmolality |
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how do you determine serum osmolality
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measured with osmometer or calculated from serum biochemistry panel
Osm = 1.86 ([Na] + [K]) + ([BUN]/2.8) + ([glucose]/18) Na & K are in mEq/L or mmol/L BUN & Glu are in mg/dl |
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rapid changes in _____ can cause cellular edema
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extracellular (serum) osmolality
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rapid changes in ______ can cause hemolysis
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extracellular (serum) osmolality
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What is the source of circulating proteins
1. albumin 2. B lymphocytes 3. alpha and beta globulins 4. coagulation factors (except VIII) 5. Coag Factor VIII 6. plasma cells |
1. hepatocytes
2. lymphoid tissue 3. hepatocytes 4. hepatocytes 5. endothelial cells 6. lymphoid tissue |
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what are acute phase proteins?
where are they made? |
alpha and beta globulins
made by hepatocytes |
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How do you measure total protein
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biuret method
- colorimetric, spectrophotometric technique - detects peptide bonds - highly specific for protein measurement - used on serum or plasma (g/dl) - accurate for plasma, serum, body cavity effusions (when 1-10 g/dl) precipitation and dye-binding methods - quantify small amts of protein fround in urine/ CSF (mg/dl) refractometry - changes in refractive index are proportional to protein concentration - accurate when conc 1-10 g/dl - usually used for plasma/ body cavity effusions - specimen must be clear (lipemia/ hemolysis cause false increase) - other solutes may affect refractive index of sample (glucose/ urea/ Na/ Cl) causing false increase |
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how do you measure albumin (g/dl)
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Bromcresol green (BCG)
- dye binding method - most used in vet labs - note useful in birds/ reptiles (use serum or plasma protein electrophoreisis) bromcresol purple (BCP) - dye binding - acurate in humans in human specimens only - false low in animals |
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how do you measure globulin (g/dl)
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calculated
TP-albumin = globulin can be separated from albumin and directly quantified by serum protein electrophoresis screening tests for failure of passive transfer of colostral antibody to foals and calves - glutaraldehyde coag test - zinc sulfate turbidity test - latex agglutination - membrane filter ELISA |
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how do measure for failure of passive transfer in calves/ foals
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screening tests for failure of passive transfer of colostral antibody to foals and calves (globulins)
- glutaraldehyde coag test - zinc sulfate turbidity test - latex agglutination - membrane filter ELISA |
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how do you measure fibrinogen (mg/dl)
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heat precipitation method
- crude test - usually done in conjuction with large animal CBC to screen for Hyperfibrinogenemia - NOT sensitive enough to detect hypofibrinogenemia |
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______is the darkest band (and therefore the highest peak) for mammals on protein electrophoresis
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albumin
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what test is used to check for hypofibrinogenemia?
hyperfibrinogenemia? |
hypo
- (modified) thrombin time hyper - heat precipitation test |
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when would you want to use protein electrophoresis
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evaluation of hyperglobulinemia
- monoclonal or polyclonal evaluation of protein concentrations in birds and reptiles 6 regions in dogs and cats - albumin - alpha 1 - alpha 2 - beta 1 - beta 2 - gamma 4 regions in cattle - albumin - alpha - beta - gamma |
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HYPERPROTEINEMIA
what do you expect with each of the following protein abnormalities 1. Relative (dehydration) 2. Hyperalbuminemia 3. Hyperglobulinemia 4. Inflammation 5. Neoplasia 6. Hyperfibrinogenemia |
1. relative (dehydration)
- water loss concentrates all plasma proteins proportionately - increased TP - increased albumin - increased globulin - increased hematocrit 2. hyperalbuminemia - usually relative (dehydration) - absolute increase rare (may occur with glucocorticoid administration due to increased albumin synethesis or life-span) 3. hyperglobulinemia - upregulated during inflammation/infection - increased [glob] due ti increased Ig's - +/- acute phase proteins - +/- complement 4. inflammation - infectious or noninfectious (necrosis/ neoplasia/ immune mediated) - Pos acute phase rxn ~hepatic synthesis of acute phase proteins increased w/in hrs of inflammatory stim and persist as long as stim present ~ alpha 1 & alpha 2 globulins ~ fibrinogen ~ serum amyloid A ~ C reactive protein (dogs) - negative acute phase rxn ~ hepatic synthesis of neg acute phase proteins is decreased w/in days to weeks of inflammatory stimulus ~ albumin ~ transferrin - delayed response ~ chronic stimulation causes increase in serum/plasma proteins in 1-3 weeks after onset of infammation ~ IgG ~ gamma-globulins ~complement (C3) ~ may see polyclonal gammopathy which may extend from gamma region to beta region (broad base) 5. neoplasia - monoclonal gammopathy - tall narrow peak in beta or gamma region 6. hyperfibrinogenemia - inflammatory or neoplastic dz (fibrinogen is a pos APP) - impt indicator of acute inflammation in cattle & horses |
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decribe the positive acute phase inflammatory reaction
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APPs increased w/in hrs of inflammatory stim and persist as long as stim present
~ alpha 1 & alpha 2 globulins ~ fibrinogen ~ serum amyloid A ~ C reactive protein (dogs) |
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describe the negative acute phase inflammatory rxn
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hepatic synthesis of neg acute phase proteins is decreased w/in days to weeks of inflammatory stimulus
~ albumin ~ transferrin |
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what do you expect to see in a protein electrophoresis if a plasma cell becomes neoplastic (myeloma)
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monoclonal gammopathy
- tall, narrow spike in beta or gamma globulin region need immunoelectrophoresis to identify Ig glass involved and confirm monoglonal gammopathy |
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what are the differentials for a monoclonal gammopathy
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neoplasia of plasma cell (myeloma)
canine ehrlichiosis canine leishmaniasis FIP (the last 3 are not true monoclonal gammopathy, they are restricted polyclonal or oligoclonal) |
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HYPOPROTEINEMIA
What would you expect to see with (and what are causes of) 1. relative (overhydration/ fluid retention) 2. Hypoalbuminemia a. Increased loss from vascular space b. decreased synthesis by liver 3. hypoglobulinemia 4. hypofibrinogenemia |
1. relative (overhydration/ fluid retention)
- all plasma proteins diluted proportionately - low TP - low albumin - low globulin - see with overzealous IV fluid administration - intersitial water shifts into plasma after acute blood loss - with CHF 2. hypoalbuminemia a. increased loss - hemorrhage ~ HCT normal (initially) ~ HCT and plasma proteins decrease w/in 2-3 hrs as diluted by interstitial fluid ~ return to normal w/in 1 wk of resolution - protein losing nephropathy ~ due to glomerulonephritis or renal amyloidosis ~ damage to glomerulus -> loss of negative charge across glomerular basement membrane -> allows albumin through (but not globulins) -> albumins lost in urine - protein losing enteropathy ~ generalized SI mucosal or lymphatic dz (like, say, genetic freaks who don't know they're genetic freaks...) -> prohibits intestinal absorption and transport of proteins -> albumin and globulins lost in feces - severe exudative skin dz/ burns ~ lose albumin and globulins b. decreased synthesis - hepatic insufficiency ~ < 20% functional mass remaining ~ chronic liver dzs (fibrosis/ chronic inflammation, portosystemic shunts, neoplasia) - severe malabsorption/ maldigestion ~ increased protein catabolism -> fewer AA available for protein synthesis ~ generalized small intestinal dz or exocrine pancreatic insufficiency - cachexia ~ due to chronic inflammation, neoplasia, starvation - inflammation ~ albumin is neg acute phase protein - plasma cell neoplasia (myeloma) ~ marked hyperglobulinemia -> increased COP -> down regulation of albumin production 3. hypoglobulinemia - increased loss from vascular space ~ glob lost with albumin in hemorrhage, PLE, and exudation (not PLN) - decreased Ig synthesis from lymphocytes ~ SCID of arabian or appaloosa foals or dogs (basset/ welsh corgi/ JRT) -> congenital failure to produce B an T lymphocytes -> no Ig produced ~ chemo ~ infections causing lymphoid hypoplasia (ex retroviral) ~ severe malabsorption, maldigestion, malnutrition (think of genetic freaks among you...) - failure of passive colostral transfer ~ low gamma glob conc 4. hypofibrinogenemia (manifests as increased bleeding) - DIC -> fibrinogen consumed - congenital deficiency (rare) |
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in what situation would you expect albumin loss but no globuin loss
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protein losing nephropathy
due to glomerulonephritis or renal amyloidosis damage to glomerulus - > loss of neg charge across basemement membrane -> allows albumin through but not globulins (b/c they are too large) albumin lost in urine |
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What do you expect protein values too look like with dehydration?
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TP - increased
Alb - increased Glob - increased |
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What would you expect the protein values to look like with chronic inflammation
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TP - increased
Alb - normal to decreased Glob - increased |
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What would you expect the protein values to look like with glomerular dz
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TP decreased
Alb - decreased Glob - normal |
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What would you expect protein values to look liek with failure of passive transfer
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TP - decreased
Alb - normal Glob - decreased |
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What would you expect protein values to look like with protein losing eneteropathy
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TP - decreased
Alb - decreased Glob - decreased |
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What would you expect protein values to look like with hemorrhage
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TP - decreased
Alb - decreased Glob - decreased |
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What would you expect protein values to look like in a Marsh Classification 3 Celiac patient (aka- severe villous blunting with no normal villi seen)
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TP - decreased
Alb - decreased Glob - decreased b/c severe malabsorption |
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A heat precipitation test is used to detect what
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hyperfibrinogenemia
(hyopfibrinogenemia is measured with a modified thrombin time) |
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3 classifications of anemia *and what they are characterized by (ie reticulocytosis or not)*
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nonregenerative
- no reticulocytosis preregenerative - impending reticulocytosis regenerative - reticulocytosis - except in those damn horses (b/c won't be there, except for when it is, b/c it's raining in the sudan) |
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how do mature RBC differ from reticulocytes
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mature
- smaller - normal Hgb - no RNA - pink staining (normochromasia) - neg NMB staining reticulocyte - larger - lower Hgb - contains RNA - purple staining (polychromasia) - pos NMB staining |
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1. Are reticulocytes normally present in the circulation of
a. dogs & cats b. cattle & other ruminants c. horses 2. Are reticulocytes increased with regenerative resonse in a. dogs & cats b. cattle & other ruminants c. horses |
1. a. yes (low #s)
b. no c. no 2. a. yes b. yes c. no (damn you Mr. Ed) |
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describe the anemia of inflammation
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normocytic normochromic
decreased erythropoiesis - functional iron deficiency (mediated by hepcidin) ~ high storage form of iron (fxnal sequestration) and low serum iron - inhibition by other cytokines shortened RBC life span |
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most regenerative anemias are _____ (Macro/normo/microcytic), ____ (macro/normo/ microchromic)
non-regenerative anemias? |
regenerative
- most are normocytic normochromic non-regenerative - most are normocytic normochromic - can be macrocytic hypochromic |
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describe hepcidin and its effect on inflammatory anemia
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normall expression of hepcidin is low
- increased in inflammation ferroportin normally expressed on cells *such as luminal GI tract cells & macrophages* - allows iron inside cell to get out into the plasma - it also serves as a receptor for hepcidin when hepcidin binds, ferroportin is moved inside the cell and is degraded get decreased iron absorption and decreased release of iron from storage fxnal iron deficiency anemia |
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what is hepcidin's effect in a nutshell
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inhibits intestinal absorption fo iron and release of iorn stored in macrophages
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when do you see true iron deficiency?
what does it look like _____cytic, _____chromic anemia |
in regenerative or nonregenerative anemia
usually secondary to chronic hemorrhage (esp GI) - due to chronic loss of Hgb into extracellular environment - HW - intestinal neoplasia - GI neoplasia rarely due to nutritional deficiency (unless you have celiac's dz and can't absorb it from your diet) microcytic, hypochromic anemia - microcytosis develops first |
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is blood loss normall regenerative or nonregenerative
in the spirit of Dr. Henry, when is it not |
normally regenerative
with the exception of iron deficiency b/c it can be regen or nonregen |
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why do you see anemia with CRF
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decreased erythropoiesis
secondary to decreased EPO production by JG cells |
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how does thyroid fxn affect anemia?
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hypothyroidism
- decreased erythropoiesis - decreased EPO production - decreased EPO responsiveness - someone in our class is screwed, and it's not me :) hyperthyroidism - 10-25% of peopole are anemic - decreased erythrocyte survival? - ineffective erythropoiesis? - associated w/ increased Heinz bodies in cats (but not all affected cats are anemic) - may cause erythrocytosis (secondary/ appropriate) |
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increased heinz bodies in cats are associated with
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hyperthyroidism
diabetes mellitus lymphoma |
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hypoadrenocorticism (addison's dz) has what effect on erythropoiesis
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decreased erythropoiesis
glucocorticoids interact with EPO and SCF to promote erythropoiesis anemia may be masked by hypovolemia - due to polyuria - don't produce aldosterone normally non-regenerative anemia |
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how does chronic liver dz affect erythropoiesis
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non-regenerative anemai
- inflammation - abnormal metabolism of AAs/ Proteins/ Lipids - defective Fe handling Portosystemic shunts - often microcytic (mx not understood) |
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in what infectious diseases do you expect to see thrombocytopenia with anemia
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FeLV
EIAV (equine anemia virus) infect erythropoietic cells - direct suppression of early stage erythropoietic cells - inflammation - immune mediated hemolysis |
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FeLV (in relation to hemopoiesis)
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causes wide spectrum of hematologic abnormalities
often macrocytic in the absence of reticulocytosis subgroup C (uncommon) assoc with erythroid aplasia |
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Cat CBC shows macrocytosis (without normal pattern of macrocytic hyperchromic regenerative anemia). What is the dx
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FeLV
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toxic injury to marrow shows what on CBC
give examples that could cause this |
nonregenerative anemia
pancytopenia - generalized suppression of hematopoiesis chemical agents - chemo - hyperestrogenism - bracken fern toxicity irradiation |
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myelophthisis causes what kind of anemia
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non-regenerative
fibrosis neoplasia (hematopoietic or metastatic) osteopetrosis replacement of hematopoietic tissue in marrow with other tissue (usually fibrous CT) |
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nonregenerative IMHA
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prob occurs when erythroid cells destroyed before fully mature
- dx based on exclusion and response to therapy bone marrow findings variable - pure red cell aplasia (or very little erythropoiesis) to erythroid hyperplasia most IMHA is regenerative - but if targeting early stages (before mature) in bone marrow stage - can see bone marrow with erythroid hyperplasia but it itsn't making it out into the periphery it isn't the norm, but it is possible |
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name some (rare) causes of anemia
including nutritional (not iron) and congenital |
nutritional deficiencies
- copper (disrupts iron metabolism) - folate or cobalamin (B12) *nutritional or inherited* congenital dyserythropoiesis - Engl Springer Spaniels - Polled Herefords |
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anemia in animals with neoplasia is most often ____ (regen/ nonregen)
why |
non-regenerative
disease related factors - inflammation - hemorrhage - hemolysis (secondary IMHA) - impaired renal fxn - nutritional deficiencies - myelopthisis Tx related factors - common complication of chemo/ radiation - secondary hemolytic anemia (in people) has a neg impact on quality of life, prognosis, and response to therapy neoplasia can be regenerative (ala Henry) |
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describe erythrocytosis
what effect does it have on MCH/ MCHC |
Increase in total number of RBC
not increase in Hgb so no increase in MCH/ MCHC |
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how will lipemia affect your CBC
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falsely increased Hct (b/c degree to which light bends is not just due to protein but also to lipids)
false increase Hgb MCH/ MCHC increased |
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define erythrocytosis
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increased circulating RBC mass
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what does the erythrogram show increases in for erythrocytosis
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RBC (#/ul)
Hct (%) - porportion of blood on volume displacement basis Hgb (g/dL) |
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what are some non-pathologic causes of absolute erythrocytosis
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breed variations
physiologic doping idopathic (mild) |
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what is relative erythrocytosis
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not really more RBC, just looks like it
Hemoconcentration - dH2O - endotoxemia (movement of water from intravascular to extravascular - not true dehydration) redistribution of RBC - splenic contraction (esp horses) |
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what are the causes of primary erythrocytosis
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primary = non EPO dependent
polycythemia vera - type of hematopoietic stem cell neoplasia mutations affecting EPO receptor or transcriptional regulation of EPO |
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what are causes of secondary appropriate erythrocytosis
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right to left shunts (hypoxia)
- PFO - PDA pulmonary dz (hypoxia) - due to less oxygen exchange hyperthyroidism - increased demand for O2 - direct effect of thyroid hormone on erythropoiesis? - assoc with anemia? |
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appropriate vs inappropriated erythrocytosis
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appropriated
- increased EPO in response to decreased O2/ anemia - increased RBC in 3-4 days (reticulocyte) - normally takes 5 days to get reticulocyte into blood, but in the presence of EPO, there is a shorter transit time inappropriate - not in response to anemia/ hypoxia |
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syndrome
malignant neoplasia benign neoplasia |
syndrome
- collection of symptoms malignant neoplasia - characterized by spread (metastasis)/ invasion benign neoplasia - no metastasis or invasion |
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secondary inappropriate erythrocytosis causes
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Renal lesions secreting EPO
- neoplasia - cysts extra-renal neoplasia secreting EPO |
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what are some non-pathologic causes of erythrocytosis (4)
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breed variations
physiologic doping idiopathic |
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how do you diagnose the different types of erythrocytosis
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relative
- hx - PE - routine b/w - dx straight forward - plasma protein in tandem with PCV 2ary appropriate - clinical signs - lab data - impaired oxygenation - hyperthyroidism other (exclusion/ additional testing) - supports dx of 2 inappropriate: ~ renal or extrarenal tumor ~ high plasma [EPO] - supports dx of primary ~ normal or decreased plasma [EPO] |
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hyperviscosity syndrome
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increased viscosity, impaired blood flow, distention of microvasculature
increased risk of tissue hypoxia and thrombosis or hemorrhage clinical signs - erythematous mm - prolonged CRT - congested scleral or retinal blood vessels - evidence of thrombosis or hemorrhage - signs (eg neuro) related to affected organ system(s) |
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causes of regenerative anemia
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blood loss
hemolysis - immune mediated - fragmentation - infectious - metabolic - heinz body |
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what is the term for increased MCV?
decreased MCHC? |
increased MCV
- macrocytosis decreased MCHC - hypochromasia |
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________ is almost always artifact (macrocytosis/ microcytosis/ hyperchromasia/ hypochromasia
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hyperchromasia
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most regenerative anemias are ___cytic, ____chromic
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normocytic normochromic
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what does an iron deficient anemia look like
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microcytic, microchromic
microcytic, normochromic |
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agglutination has what effect on MCV
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false increase
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what 2 entities represent the same cell stained 2 different ways (Romanowsky & NMB) which represent regeneration
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Romanowsky Stain
- polychromatophilic macrocyte NMB - Reticulocyte |
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______ is a visual suggestion that we have a regenerative anemia
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polychromasia
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what is the best way to determine if you have a regenerative anemia
how can you determine if you may have regeneration if all you have is a blood smear? |
Reticulocyte
look for polychromasia |
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anisocytosis
variation in cell size |
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suggestions of regeneration
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polychromasia/ reticulocytosis
anisocytosis - variable size Nucleated RBC - metarubricyte basophilic stippling - usually only in ruminants with regen anemia - presence of aggregated ribosomes on Romanowsky stained smear howell-jolly body - nuclear remnant |
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If you see a dog with nucleated RBC and basophilic stippling, what is your dx
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lead toxicity (not regenerative anemia)
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If you see a cow with nucleated RBC and basophilic stippling, what is your dx
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regenerative anemia
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When is rubricytosis appropriate?
inapproprite |
rubricytosis = nucleated RBC present
appropriate - regeneration - in presence of reticulocytes inappropriate - marrow damage (necrosis/ inflammation/ endotoxemia/ heat stroke/ neoplasia) - extramedullary hematopoiesis - splenic contraction or splenectomy - lead poisoning with basophilic stippling |
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____ is THE BEST method for determining marrow response to anemia
what are the #'s for reference how long does it take |
Reticulocyte concentration/ count
dog = >80,000/ul cat = >60,000/ul takes 2-3 days after initiation of anemia |
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nucleated RBC (metarubricyte)
basophilic stippling - presence of aggregated ribosomes on Romanowsky stained smear - sign of regen in ruminant - sign of lead poisoning in dog |
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Spherocyte
Must - Look smaller - No central pallor - Be round Halfway eaten cells |
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Schistocytes
Sheared RBC (got clothes-lined by something) - Altered vasculature - Strand of fibrin from inflammation |
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Acanthocytes
RBC with at least 3 club shaped projections Occur due to visceral problem (esp splenic/ hepatic) May be pathognomonic in visceral hemangiosarcoma Don’t mistake with Echinocytes/ crenation (spikey but not clubbed) |
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Echinocyte/crenation vs. Acanthocyte
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Echinocytes/ crenation
- Spikey but not clubbed - Rattle snake venom Acanthocytes - RBC with at least 3 club shaped projections - Occur due to visceral problem (esp splenic/ hepatic) |
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Heinz Body
Aggregated denatured Hb Blue on NMB Clear on romanowsky stain Often protruding from cell Dogs - Never normal - Due to oxidative damage Cats - See more often |
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evidence of hemolysis consists of
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pre-hepatic hyperbilirubinemia and bilirubinruia
- overflow of unconjugated bilirubin from macrophages (conjugated in K9 kidney) - overflow of conjugated bilirubin from liver - results in bilirubinuria hemolyzed plasma hemoglobinuria erythrocyte chagned associated with causes of hemolysis |
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normal RBC breakdown/ bilirubin metabolism
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In liver it is broken down into
Protein Hemoglobin - Broken down into Heme and biliverden Biliverdin turned into unconjugated bilirubin - Goes to blood - Unconjugated bilirubin hooks up with albumin -> conjugated bilirubin - Exits biliary tract |
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Hemolytic anemia findings
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poikilocytosis or cell inclusions
neutrophilic leukocytosis reticulocytosis splenomegaly |
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what does the CBC of a IMHA case look like
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PCV down
HCT down MCV up MCHC normal Reticulocytosis (uncorrected and corrected) macrocytic normochromic regen anemia Poikilocytosis or cell inclusions Neutrophilic leukocytosis Inflammatory leukogram +/- Spherocytosis +/- Agglutination +/- |
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what does the leukogram of a IMHA case look like
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WBC up
Segs up Bands normal lymphs down monos up |
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What is the horse’s HCT and TP minutes after the deep laceration is made? 12 hours? 5 days? 2 weeks?
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evidence of hemolysis consists of
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pre-hepatic hyperbilirubinemia and bilirubinuria
hemolyzed plasma hemoglobinuria erythrocyte changes associated with causes of hemolysis |
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intravascular vs extravascular hemolysis
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IV
- Hgb - Released into plasma (red plasma in HCT tube) - Freely filtered to urine EV - pre-hepatic hyperbilirubinemia and bilirubinruia - overflow of unconjugated bilirubin from macrophages (conjugated in K9 kidney) - overflow of conjugated bilirubin from liver results in bilirubinuria |
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What kind of bilirubin can be excreted in urine
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conjugated bilirubin
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prehepatic hyperbilirunemia causes
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overflow of conjugated bilirubin from liver
overflow of unconjugated bilirubin from the macrophage |
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what do you see with IMHA
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Poikilocytosis or cell inclusions
Neutrophilic leukocytosis Reticulocytosis Splenomegaly Inflammatory leukogram +/- Spherocytosis +/- Evans syndrome +/- Agglutination +/- Coombs’ Test positive +/- |
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signs of hemolysis (IV vs EV)
how does normal RBC breakdown/ bilirubin metabolism occur |
IV
- Hemoglobin released into plasma -> red plasma in HCT tube -> freely filtered into urine EV - Pre-hepatic hyperbilirubinemia and bilirubinemia • Overflow of unconjugated bilirubin from macrophages (Conjugated in canine kidney) • Overflow of conjugated bilirubin from liver • Results in bilirubinuria Normal • In liver, it is broken down into: o Protein o Hemoglobin: broken down into Heme and biliverdin Biliverdin turned into unconjugated bilirubin-> goes to blood o Unconjugated bilirubin hooks up with albumin -> conjugated bilirubin - Exits biliary tract |
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causes of IMHA
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Idiopathic or autoimmune
Drug induced Isoimmune (NI) Blood transfusion |
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agglutination
held together by antibodies |
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rouleaux
formation due to reduction in membrane charge |
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IMHA CBC & Leukogram
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CBC
o PCV down o HCT down o MCV up o MCHC normal o Retics up (uncorrected) - Corrected: still up, regenerative o Macrocytic, normochromic regenerative anemia • Leukogram: inflammatory leukogram +/- o WBC up o Segs up o Bands normal o Lymphs down o Monos up |
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IMHA blood smear
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spherocytosis +/-, agglutination +/-
Hemolysis, icterus, spherocytes, clumping of RBCs Clumping • Agglutination: antibodies are holding RBCs together • Rouleaux: formation due to reduction in membrane charge o Normal in horses and cats o Will disperse when saline is added (“stack of coins”) |
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Signs of IMHA
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o Fever
o Anorexia o Weakness o Prolonged CRT o MM pale and icteric |
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Mechanism of IMHA
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Macrophages get a little premature w/hemolysis, release inflammatory cytokines
Leads to leukocytosis and presence of spherocytes Activates C’, leads to IV hemolysis |
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signs of fragmentation
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• IV coagulation
• Vasculitis • Hemangiosarcoma • Caval syndrome • Cardiac valvular disease • Schistocyte |
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babesia canis
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mycoplasma hemofelis
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Anaplasma marginale
• Looks like a Howell Jolly body - Usually seen on more immature RBCs - on margin of mature RBCs |
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Heinz body
ingestion of onions, tylenol, red maple leaves oxidation of sulfhydrily groups on globin chain denaturation and precipitation of globin chain heinz body forms and adheres to inside of RBC membrane |
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What are Heinz bodies?
What causes them? What is the mechanism? |
Aggregated denatured hemoglobin
Causes • Ingestion of onions, Tylenol, maple leaves, acetaminophen, propylene glycol, skunk musk, Zn toxicity, idiopathic • Cats have more sulfhydryl groups, and their spleen is less able to get rid of Heinz bodies, can be seen in normal cats o Seen w/ hyperthyroidism, diabetes mellitus and LSA Mechanism • Eat bad thing -> oxidation of sulfhydryl groups on globin chain-> denaturation and precipitation of globin chain-> heinz body forms and adheres to inside of RBC membrane |
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6 causes of Heinz bodies
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Onions and garlic
Acetaminophen Propylene glycol Skunk musk Zinc toxicity Idiopathic |
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6 causes of Heinz bodies
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Onions and garlic
Acetaminophen Propylene glycol Skunk musk Zinc toxicity Idiopathic |
