Circ & Resp 2: Clin Path S1 Flashcards
after trauma, how long does it take for an animal to show anemia in bloodwork?
could take an HOUR
3 things seen with ACUTE BLOOD LOSS (mention how kidneys respond/timing, another notable organ/timing, and treatment-related)
(1) DECREASED OXYGEN (from decreased oxygen-carrying capacity)
–> kidneys respond by making erythropoietin to stimulate RBC production in bone marrow
–> response or regeneration of RBCs takes 2-3 days
(2) SPLENIC CONTRACTION
–> spleen contracts to release RBCs and platelets
(3) FLUIDS
–> either ADMINISTERED or REDISTRIBUTED
–> causes hemodilution and DECREASED PLASMA PROTEIN and DECREASED ALBUMIN/GLOBULIN (serum proteins)
CBC findings for acute blood loss (5, mention reasons for 2 of them)
(1) Decreased PCV
(2) Concurrent decrease in total protein (albumin and globulin)
(3) Decreased platelets
–> Get CONSUMED by trying to cause clotting, still circulating due to splenic contraction
–> PRIMARY = thrombopathia
–> SECONDARY = vitamin K antagonism, hepatic failure
(4) Increased BUN and NORMAL creatinine
–> Blood broken down is a PROTEIN so increase ammonia –> increased BUN (blood urea nitrogen)
–> Often seen in GI hemorrhage
(5) SEVERE THROMBOCYTOPENIA
–> Less than 25,000 platelets
–> COULD BE THE CAUSE OF BLEEDING
Dog RBCs description
normal sized WITH CENTRAL PALLOR because biconcave disc
Cat/Horse RBCs description
Smaller red cells with LACK of central pallor
Cow RBCs description (hint: compare to dogs)
SMALLER than dogs WITH CENTRAL PALLOR
Goats/sheep RBCs description
MINIMAL CENTRAL PALLOR, SOME OF THE SMALLEST RBCs
Camelid RBCs description
Have elliptical RBCs
Birds/reptiles RBCs description
odd shape/nucleated RBCs
which values are measured (3) vs. calculated (2) on a CBC using a hematology instrument?
MEASURED (directly determined)
(1) Hemoglobin concentration
(2) RBC count in millions
(3) MCV
CALCULATED (determined)
(1) Hematocrit
(2) MCHC
macrocytic & what can cause it
when MCV is ABOVE reference range, RBCs are LARGER THAN NORMAL
CAUSE?
Regenerative, accelerated erythropoiesis resulting in skipped division in larger cells
microcytic & what can cause it
when MCV is BELOW reference range, RBCs are SMALLER THAN NORMAL
CAUSE?
Iron deficiency anemia, less hemoglobin causing extra division of erythropoiesis
normocytic
MCV is within reference range
hypochromasia & what can cause it
when MCHC is BELOW reference range and LESS Hb in RBC, looks PALE (not as red)
CAUSE?
Regenerative anemia but now less Hb per cell volume because MORE RBCs
normochromic
when MCHC is WITHIN reference range
what does regenerative anemia look like with RBCs?
MACROCYTIC and HYPOCHROMASIA (large and pale)
what does iron deficiency anemia look like with RBCs?
MICROCYTIC and HYPOCHROMASIA (small and pale)
what does a CBC include?
Provides information on erythrocytes, leukocytes, platelets, and CAN include plasma proteins (albumin, fibrin, globulin)
where are RBCs made?
Produced in the bone marrow in response to erythropoietin made by the kidneys
can also be produced in extramedullary tissues like the spleen or liver
function of RBCs?
to synthesize Hb, which binds and transport oxygen
hemoglobin structure (include iron states)
each heme subunit contains a Fe ion within a porphyrin ring
Fe2+ = CAN CARRY OXYGEN
Fe3+ = METHEMOGLOBIN, CANNOT CARRY OXYGEN
how many Hb molecules do RBCs contain?
hundreds to millions
iron deficiency anemia and heme
diminished production of heme –> less RBCs/anemia
when is methemoglobin formed? what happens when it’s formed?
when RBCs undergo significant oxidative injury so they cannot carry oxygen anymore (Fe3+)
how long do RBCs circulate for most veterinary species (non-exotic)?
90-120 days
about __% of RBCs are ___ & ___ ___ daily due to ___
1, produced, broken down, senescence
what stimulates RBC production in the bone marrow? where is it made? what kind of tissue does it require?
erythropoietin
made by renal cortical cells
requires functional, adequate renal cortical tissue
what 3 morphological changes occur for RBCs during development?
(1) cells become SMALLER
(2) cytoplasm changes from blue to red with increased Hb
(3) extrusion (removal) of nucleus
how many RBCs are in blood on average?
Between 6-10 million/uL
stages of RBC development (7)
- rubriblast
- early rubricyte
- middle rubricyte
- late rubricyte
- metarubricyte
- reticulocyte
- mature erythrocyte
what stage of RBC development do they start making Hb?
early rubricyte (2)
what stage of RBC development do they stop dividing? why?
late rubricyte (4)
due to CRITICAL CONCENTRATION OF Hb
characteristics of a reticulocyte
NO NUCLEUS because extruded after late rubricyte stage
still contains ORGANELLES AND RNA
hematocrit (HCT) definition
% of blood volume taken up by RBCs
MEASURED BY MACHINE via RBCs and MCV
what two values are often used to characterize anemia? what specifically are they looking to evaluate?
hematocrit (HCT) and packed cell volume (PCV)
they evaluate RBC density!!
packed cell volume (PCV) definition
% of blood volume taken up by RBCs
MANUALLY CALCULATED using a microhematocrit tube and microcentrifuge
hemoglobin count definition (on laboratory)
grams of Hb/100 mL of blood MEASURED BY ANALYZER
RBC count (on laboratory)
amount of RBCs/unit of blood MEASURED BY ANALYZER
if we have blood loss/hemolysis or decreased oxygen tension, what occurs in regards to RBC development? (**hint, mention what specific part of the organ does the first step, the process, and how long it takes)
renal cortical cells secrete EPO and tell bone marrow to undergo reticulocytosis within 2-3 days once these changes occur
how long do reticulocytes remain in blood? what happens after this period?
1-2 days, then become mature RBCs
horses and related species do not have ___ released
reticulocytes
no reticulocytosis = we do not have regenerative anemia (T/F and explanation)
FALSE
can have anemia with lackluster regenerative response
reticulocytosis definition
erythroid regeneration/increased erythropoiesis
reticulocyte vs. polychromasia
SIMILARITIES?
(1) BOTH are the stage before mature RBC
(2) BOTH appear bluish on microscopic stains
DIFFERENCES?
(1) Reticulocytes are enumerated by MACHINES, polychromatophils are semi-quantitatively determined on blood smears
(2) grading scales are subjective and variable for polychromatophils (slight, mild, moderate; marked 1+, 2+, 3+); % and absolute counts in reticulocytes
(3) DEGREE OF POLYCHROMASIA AND THEREFORE REGENERATION DEPENDS ON THE AMOUNT OF ORGANELLES/RNA PRESENT IN RETICULOCYTES; whereas reticulocytes are given in an exact number to determine regeneration
All ____ RBCs are ____, but not all ____ have enough ____ & ____ to be _____
polychromatophilic, reticulocytes, reticulocytes, RNA, organelles, polychromatophilic
AUTOMATIC vs MANUAL reticulocyte enumeration
AUTOMATIC
–> occurs with most hematology analyzers
–> absolute count
MANUAL
–> equal parts blood and new methylene blue for 10-15 minutes to aggregate organelles/RNA in RBCs to make a blue-speckled reticular pattern
–> 1000 RBCs counted and reticulocytes are a % out of these RBCs
absolute reticulocyte number (definition, formula, and what we do with the value)
number of reticulocytes per uL of blood
absolute reticulocyte number = reticulocyte % x RBC count (in millions)
COMPARE THIS TO REFERENCE RANGE TO DETERMINE IF REGENERATIVE ANEMIA IS OCCURRING
CORRECTED reticulocyte % (CRP, how often it’s used, formula, normal ___ values for dog/cat/cow)
NOT OFTEN USED, incorporates PCV
CRP = reticulocyte % x (patient PCV/normal PCV)
normal PCV values
dog = 45
cat = 35
cow = 35
2 reasons we could have reticulocytosis WITHOUT anemia?
(1) SUBCLINICAL BLEEDING
ex = intermittent intraabdominal bleed
- patient hasn’t developed clinical signs but still hemorrhaging somewhere, erythropoiesis was activated
(2) PATIENT’S NORMAL VALUES FOR RETICULOCYTES FALLS OUTSIDE REFERENCE RANGES
mean corpuscular volume (MCV)
MEASURED average volume of circulating RBCs
mean corpuscular hemoglobin concentration (MCHC)
CALCULATED average concentration of Hb within circulating RBCs
cellular hemoglobin concentration mean (CHCM)
MEASURED more accurate MCHC with in vivo or in vitro hemolysis or lipemia
mean corpuscular hemoglobin (MCH)
NOT TYPICALLY USED
CALCULATED concentration of Hb per cell NOT AN AVERAGE
iron deficiency anemia findings (4)
(1) Decreased MCV AND MCHC
(2) Can be REGENERATIVE or NON-REGENERATIVE
–> Reticulocytes can be NORMAL OR INCREASED
(3) Can see MICROCYTES and HYPOCHROMASIA
(4) Can also see SCHISTOCYTES, KERATOCYTES, AND ACANTHOCYTES
differential for RBCs that are NORMOCYTIC and NORMOCHROMIC?
ANEMIA OF CHRONIC DISEASE, or many other types of anemia
INCREASED MCV differentials (5)? another word for increased MCV?
MACROCYTIC, RBCs are larger than normal (immature likely)
(1) Erythroid regeneration
SUPPORT: RETICULOCYTOSIS, +/- concurrent DECREASED MCHC
(2) RBC agglutination (artificially high MCV)
(3) Cobalamin or folate deficiency
(4) Poodle
(5) FeLV infection
INCREASED MCHC differential (with 3 causes)? another term increased MCHC?
HYPERCHROMASIA/HYPERCHROMIC
IN VITRO (outside cells) or IN VIVO (in cells) ARTIFACT
(1) Intravascular hemolysis –> Hb is in blood because HEMOLYSIS
(2) Numerous Heinz bodies
(3) Lipemia (spectral interference)
Why do we see microcytic cells (LOW MCV) in iron deficiency anemia?
because we need IRON to make HEMOGLOBIN, so WITHOUT ENOUGH IRON = NOT ENOUGH HEMOGLOBIN, and that means WE DON’T REACH CRITICAL CONCENTRATION OF HEMOGLOBIN AT LATE RUBRICYTE STAGE to tell cell to STOP DIVIDING
often see MICROCYTIC AND HYPERCHROMIC CELLS (smaller and pale)
Why do we see macrocytic cells (HIGH MCV) in erythroid regeneration?
if we have ACCELERATED ERYTHROPOIESIS, then we might have RBCs that have SKIPPED DIVISIONAL STAGES and are LARGER THAN NORMAL
causes of iron deficiency anemia (2, first one has 3 subclasses)
(1) Chronic external blood loss
–> GI or external parasitism
–> GI neoplasia causing loss of blood
–> GI ulcers
(2) Nutritional deficiency (RARE)
should we classify anemia as hyperchromic if increased MCHC? why or why not? what would be 3 reasonable explanations for this finding?
NO, RBCs cannot be oversaturated with Hb, so this must be due to INCREASED Hb in the PLASMA!
Could be from something like a traumatic blood draw, intravascular hemolysis, or even the presence of heinz bodies
what are normoblasts?
NUCLEATED RBCs, or METARUBRICYTES
nRBCs = REGENERATION, true or false?
NO, nRBCs whether INCREASED OR NOT does not indicate regeneration, although it CAN
why do we need corrected WBC counts for in-house hematology analyzers?
because they count WBCs as all NUCLEATED CELLS, but this accidentally includes nucleated RBCs (metarubricytes/normoblasts)
metarubricytosis definition
presence of nRBCs >1/100 WBCs in peripheral blood
APPROPRIATE metarubricytosis (what condition is it present with, 1 main support)
does this mean we have regenerative?
presence with REGENERATIVE ANEMIA
SUPPORT
- reticulocytosis
**METARUBRICYTOSIS ALONE DOESN’T MEAN WE HAVE REGENERATION!!
INAPPROPRIATE metarubricytosis (2 conditions it’d be in, 5 causes with the FIRST CAUSE HAVING A BUNCH OF REASONS FOR OCCURRING)
CONDITIONS
(1) presence of nRBCs (>1/100 WBCs) WITHOUT RETICULOCYTOSIS; no evidence of regenerative anemia
(2) NORMAL PCV (we have enough RBCs in blood volume)
CAUSES
(1) Damage to the MEMBRANE that separates HEMATOPOIETIC SPACES from MARROW SINUSES
–> HEAVY METAL TOXICITY (lead)
–> SEVERE ANEMIA (hypoxic bone marrow injury)
–> NEOPLASIA IN BONE MARROW
–> MARKED HYPERTHERMIA (heatstroke, malignant hyperthermia)
–> ENDOTOXEMIA/SEPSIS
–> MARROW INFECTION WITH INFILTRATES OF INFLAMMATORY CELLS
(2) SPLENIC injury
(3) Recent FRACTURE or BONE INJURY
(4) ERYTHROID LEUKEMIA (CATS)
(5) STEROID THERAPY
red cell distribution width (RDW) definition, formula
this measurement provides instrument estimate amount of variation in RBC size
RDW = (SDMCV / MCV)
when does RDW increase? what does it mean when it increases?
INCREASES when we have anemias with microcytosis (smaller than normal RBCs present), macrocytosis (larger than normal RBCs present), or reticulocytosis
HIGHER RDW = MORE VARIABILITY IN RBC SIZE
which 4 b/w values are most commonly used to evaluate RBC DENSITY/numbers? which two are both nearly identical and MOST COMMONLY USED to provide relevant clinical information (and why not the other two?)?
4 values?
PCV, HCT, HGB, RBC
2 most important/similar values?
PCV (manual), HCT (measured)
HGB = 1/3 of RBC count
RBC count = in MILLIONS, hard to appreciate change unless it’s less RBCs we’re observing
which b/w value should we evaluate to determine if there’s ERYTHROID REGENERATION?
RETICULOCYTES
rouleaux appearance of RBCs
stacked RBCs like stacks of coins
common in cats and horses during inflammation
agglutination appearance of RBCs (& 2 reasons)
grape-like clusters of RBCs due to either…
(1) AUTO- or ALLO-ANTIBODY BINDING
(2) ARTIFACT
ghost cell RBC appearance
remnant of an RBC, can be due to artifact or intravascular hemolysis
polychromatophil appearance on smear
POLYCHROMATOPHILS ARE RETICULOCYTES WITH ENOUGH ORGANELLES/RNA TO SHOW PATTERN (POLYCHROMASIA)
LOOKS BLUE
microcyte appearance on smear
SMALLER than usual RBC
Often has central pallor
if there’s enough microcytes could correspond to DECREASED MCV
macrocyte appearance on smear
LARGER than usual RBC
Often appears POLYCHROMATOPHILIC (immature RBC)
if there’s enough microcytes can correspond to INCREASED MCV
acanthocyte
- Disease if with schistocytes and keratocytes?
2; Disease if with keratocytes, schistocytes, microcytes, and hypochromasia?
- SPLENIC AND HEPATIC DISEASE
- schistocytes + keratocytes + acanthocytes = intravascular trauma/RBC shearing
- keratocytes + schistocytes + microcytes + hypochromasia = IRON DEFICIENCY ANEMIA
eccentrocyte (when do they form?)
forms SECONDARY to RBC OXIDATIVE INJURY from FUSED HB
4 causes of echinocytes, which one is most common?
- dehydration
- electrolyte disturbance
- POISONOUS snake bite
- ARTIFACT MOST COMMON
keratocyte
- give two alternate names
- what two diseases is this most commonly associated with?
- blister or helmet cell
- splenic or hepatic disease, including hemangiosarcoma and other infiltrative diseases
pyknocyte
- remnant of a ___
- why does it form?
- what happens to its membrane?
- what kind of cell does it resemble?
- remnant of an eccentrocyte
- from oxidative injury
- remnant membrane detaches from cell
- spherocyte
schistocytes
- is actually fragments of a ___
- formed due to… (and give 3 examples of diseases that’d cause this)
- commonly found in what kind of anemia?
- RBC
- RBC trauma/shearing from endocarditis, vasculitis, glomerulonephritis, etc.
- iron deficiency
spherocyte
- how is it formed?
- why is it round?
- what disease is indicated if there’s increased spherocytes?
- formed via Ab binding to RBC
- once Ab binds, loses membrane and becomes round
- IMHA
target cell
its formation is caused by what 2 explanations?
- ACCELERATED ERYTHROPOEISIS causes excess MEMBRANE for the volume, makes target shape
- hepatic disease
basophilic stippling
3 causes (hint: dogs, cattle, cats)
(1) precipitation of ribosomes in CATTLE
(2) regenerative anemia in DOGS, CATTLE, AND CATS
(3) lead poisoning which causes inhibition of enzymes in heme synthesis pathway
Howell jolly bodies in blood smears
- what are they?
- what causes them? (4, ONE with steroid use, MULTIPLE with HEMATOPOEITIC ORGAN)
- nuclear remnants in RBCs (little dots)
- CAUSES =
(1) regenerative anemia
(2) splenic disease
(3) splenectomy
(4) steroid use
water artifact in blood smears
found when cells aren’t dried sufficiently for blood smears
infectious erythrocyte organisms in CATS
**Hint, one of these isn’t in the USA!
(1) Mycoplasma hemofelis (+ small forms)
(2) Cytauxzoon felis
(3) Babesia sp. (not in the USA)
infectious erythrocyte organisms in DOGS (5)
(1) Babesia gibsoni
(2) Babesia canis
(3) Babesia microti
(4) Theileria sp
(5) Mycoplasma hemocanis
infectious erythrocyte organisms in CATTLE (3)
(1) Anaplasma marginale
(2) Anaplasma centrale
(3) Theileria spp.
infectious erythrocyte organisms in HORSES (2)
(1) Theileria spp
(2) Babesia equi
infectious erythrocyte organism in CAMELIDS (1)
(1) M. hemollamae
infectious erythrocyte organism in PIGS (1)
(1) M. suis
anemia DEFINITION
reduced HGB, RBC, and HCT (or PCV)
common associated clinical signs with anemia? (8)
(1) Pale mucous membranes (pallor)
(2) Weakness
(3) Exercise intolerance
(4) Lethargy
(5) Tachypnea
(6) Tachycardia
(7) Syncope
(8) Sudden death
response by the body to anemia?
**hints:
start with DECREASED O2 TENSION DETECTION in WHAT ORGANS, then how many days to see increase in reticulocytes, blood smear changes, MAXIMUM time for regeneration?
(1) Lowered oxygen tension in arterial blood is detected by renal cortical cells, which then produce and release EPO
(2) EPO stimulates erythropoiesis in bone marrow (sometimes also spleen or liver) and EARLY RELEASE of already produced RETICULOCYTES (24 hours earlier than normal); not necessarily causing reticulocytosis yet though
(3) Within 2-3 days, numbers of circulating reticulocytes should increase (due to increased PRODUCTION being able to take place) and we should see INCREASE in polychromasia on routinely-stained blood smears
(4) Maximum bone marrow response is at 7-10 days
3 main causes of anemia
(1) blood loss/hemorrhage
(2) decreased production of RBCs
(3) hemolysis
4 SPECIFIC causes of blood loss/hemorrhage causing anemia (WITH A LOT OF EXAMPLES)
(1) BLOOD VESSEL DAMAGE
–> Trauma
–> GI ulcers
–> Neoplasia
–> Inflammation
–> Wounds
(2) HEMOSTATIC ABNORMALITIES (can’t clot)
–> Acquired or congenital COAGULATION FACTOR DEFICIENCIES
–> Severe THROMBOCYTOPENIA (<25,000/uL)
–> Platelet function defect (vWD)
(3) PARASITISM
–> Hookworms
–> Haemonchus
—> Ostertagia
–> Coccidiosis
–> Severe external parasitism with fleas/ticks
(4) IATROGENIC
–> Repeated sampling in small patients
–> Blood donation
regenerative vs. non-regenerative causes of anemia?
NON-REGENERATIVE = DECREASED PRODUCTION OF RBCS, literally not being able to regenerate RBCs adequately
REGENERATIVE =
1. HEMOLYSIS
2. BLOOD LOSS/HEMORRHAGE
anemia definition
decrease in number of RBCs in the body
8 things to determine cause of anemia
(1) SEVERITY
can be MILD, MODERATE OR MARKED
(2) PROTEIN
- ALBUMIN AND GLOBULIN DECREASED = GI BLEED
(3) REGENERATIVE status
- Regnerative = blood loss or hemolysis, RETICULOCYTES
- Non-regenerative = decreased production
**NOT IN HORSES
(4) PATIENT information
- YOUNG ANIMAL = have lower PCV or decreased MCV, OR GI bleed
- OLDER ANIMAL = neoplasia
(5) RBC MORPHOLOGY
- Evidence of regeneration, iron deficiency, hemic parasites, evidence of oxidative injury, immune-mediated RBC targeting
(6) RBC INDICES
o IF NORMAL (MCV and MCHC), SUGGESTS ANEMIA OF CHRONIC DISEASE/OR NOT RELEVANT
- Macrocytic, hypochromic + reticulocytosis = regenerative
- Microcytic, hypochromic = iron deficiency
(7) Serum bilirubin
- BREAKDOWN PRODUCT OF HEME, so increases can be due to HEMOLYSIS
(8) BUN, creatinine, USG
- KIDNEY FUNCTION
what 3 things can cause lowered oxygen tension in body?
(1) ANEMIA (not enough RBCs)
(2) Decreased PiO2 (less oxygen available in INSPIRED air)
(3) Heart failure (poor circulation)
erythroid hyperplasia vs erythroid hypoplasia
in response to decreased RBCs, there is either INCREASED erythropoiesis (PROPER RESPONSE, HYPERPLASIA) or not (HYPOPLASIA)
routine RBC stain is called?
DiffQuik
horses and reticulocytes
HORSES DO NOT RELEASE RETICULOCYTES
difference between impedance analyzers and optical analyzers?
impedance cannot tell difference between any nucleated cell (will count nRBCs as WBCs), while optical can!
most common causes of iron deficiency anemia? (3)
**Patient ages, human causes?
- Younger patients = PARASITES, HOOKWORMS causing HEMORRHAGE
- Older patients = NSAID therapy, neoplasia
- IATROGENIC CAUSES
how do we get iron in our bodies? **hint: young animal and unlikely cause of iron deficiency?
most of it is RECYCLED upon HEMOLYSIS, small amount is NUTRITIONAL
In YOUNGER animals with lower PCV, they may be more dependent on NUTRITIONAL sources of iron, but not a likely cause
what happens in EXTREME cases of iron deficiency?
we LOSE THE ABILITY TO REGENERATE RBCs, likely to see NON-REGENERATIVE ANEMIA
effect of low iron on the INTEGRITY of RBCs?
they’re more FRAGILE, likely to exhibit POIKILOCYTOSIS
reactive thrombocytosis (2 causes)
(1) IL-6 and IL-12 –> INFLAMMATION for INCREASED PLATELET PRODUCTION
(2) Chronic EXTERNAL blood loss
in ACUTE blood loss, ___ may or may not develop
(**this is a weird one)
ANEMIA
clinical signs of ACUTE blood loss (with low PCV? give 5)
signs of LOW OXYGEN CARRYING CAPACITY
(1) sudden lethargy
(2) syncope
(3) tachycardia
(4) tachypnea
(5) weak pulse
in acute blood loss/hemorrhage, why don’t we see PCV decrease until hours to days after hemorrhagic event
because we lose blood components PROPORTIONALLY, so that after plasma fluid redistributes from the TISSUES into the VASCULAR SPACE, we see DILUTION OF NOW LOWER, REMAINING RBCs
what do platelets do in acute blood loss?
VARIABLE
INCREASED = splenic contractions
DECREASED = being used up to stop the bleeding
or normal :)
what 3 things can cause iron deficiency anemia to occur? VERY BASIC
(1) decreased erythropoiesis
(2) increased RBC fragility
(3) ongoing chronic bleeding that was never amended
lab findings for hemolysis-caused anemia? (5)
- reticulocytosis if REGENERATIVE
- hyperbilirubinemia/uria
- abnormal RBC morphology
- NORMAL proteins
- +/- hemoglobinemia
signs of IVH and EVH (extra- and intra-vascular hemolysis) on labs?
IVH
- bilirubinuria
- hyperbilirubinemia
- hemoglobinemia
- hemoglobinuria
EVH
- bilirubinuria
- hyperbilirubinemia
- TOTAL PROTEIN SHOULD BE NORMAL BC NO BLOOD LOSS
how long do RBCs live? how much is killed per day?
3-4 months, ~1% killed per day NORMALLY
which organ mostly gets rid of senescent RBCs? what are the other 2 organs?
SPLEEN
liver, bone marrow
steps for breakdown of RBC? (7, think about pigments of excrements)
- Heme + globin separated
- GLOBIN recycled
- Heme broken down into IRON AND BILIRUBIN
- IRON recycled
- BILIRUBIN is NON-SOLUBLE but is a waste process, so it GOES TO LIVER to get CONJUGATED (to make it soluble)
- Bilirubin leaves through biliary tree and through INTESTINES, converted through actions of bacteria and MAKES POOP BROWN
- Some bilirubin is reabsorbed and enters blood, goes to kidney and MAKES PEE YELLOW
dogs will have both SERUM bilirubin INCREASED when we see them have INCREASED URINE SPECIFIC GRAVITY of +1 or +2 (T/F)
FALSE.
SERUM BILIRUBIN SHOULD NEVER BE INCREASED
3 basic causes of hemolysis?
(1) immune-mediated
(2) infectious RBC disease
(3) OXIDATIVE RBC injury
rate-limiting step of RBC breakdown?
bilirubin getting out of hepatocyte into bile canaliculi
if it’s not able to pass through, BACKS UP AND GETS BACK INTO BLOOD –> hyperbilirubinemia
CAUSES INCREASE IN CONJUGATED BILIRUBIN (water-soluble)
haptoglobin system? (what is it used in, how does it work, what does it cause in b/w?)
USED IN INTRAVASCULAR HEMOLYSIS
haptoglobin “ties up” free Hb in blood since it’s potentially toxic, takes it to liver to be broken down
STILL CAUSES HYPERBILIRUBINEMIA AND BILIRUBINURIA
once haptoglobin is USED UP and cannot capture hemoglobin, then we have HEMOGLOBIN FREELY IN BLOOD and will PASS THROUGH TO KIDNEYS and we see HEMOGLOBINURIA and HEMOGLOBINEMIA
when do we expect to see ghost cells?
when we have INTRAVASCULAR HEMOLYSIS, “exploded” RBCs
what do we see in hemoglobinuria? what causes this?
red urine with NO RBCs and a BLOOD DIPSTICK
INTRAVASCULAR HEMOLYSIS
infectious causes of hemolysis in dogs, cats, horses, cattle, camelids? (name morphology with dogs, one with cats
DOGS
1. mycoplsma hemocanis
–> often from SPLENECTOMY or STEROID USAGE
- babesia
–> CANIS = in greyhounds, tear-drop shaped thing in RBC
–> GIBSONI = looks like a signet ring-shaped thing in RBC
CATS
–> Mycoplasma hemofelis
–> Cytauxzoon = causes NON-REGENERATIVE ANEMIA)
HORSES
–> Babesia equi
–> Theileria
CATTLE
–> Mycoplasma wenyonii
–> Babesia
–> Theileria
CAMELIDS
–> Hemollama
lab findings that indicate RBC oxidative injury? (6, including RBCs found on blood smear)
- INCREASED MCHC (from increased Hb or Heinz bodies)
- hemoglobinemia (INTRAVASCULAR ONLY)
- hemoglobinuria (INTRAVASCULAR ONLY)
- bilirubinuria
- hyperbilirubinemia
- RBCs on blood smear –> eccentrocytes, Heinz bodies, pyknocytes
CAUSES of oxidative RBC injury in dogs, cats, horses, sheep/goats?
DOGS
- onions
- garlic
- ZINC (found in OLD PENNIES)
CATS
- onions
- garlic
- tylenol/acetaminophen
HORSES
- dry red maple leaves
SHEEP/GOATS
- COPPER (found in OLD FEED)
what is the most common cause of hemolytic anemia?
IMMUNE-MEDIATED
difference between PRIMARY and SECONDARY IMHA?
PRIMARY = idiopathic, often in dogs
SECONDARY = from DRUGS or ALLOANTIBODIES against RBCs
IMHA using the COMPLETE phagocytosis mechanism and lab findings (where are RBCs broken down, how it happens, lab findings)
NORMAL RBC BREAKDOWN (EXTRAVASCULAR)
Broken down in SPLEEN, liver, or bone marrow
RBC broken into heme + globin –> globin RECYCLED, heme broken down into BILIRUBIN
Lab findings
- hyperbilirubinemia
- bilirubinuria
IMHA using PARTIAL phagocytosis mechanism and lab findings (mention appearance of RBCs, intra vs extra vascular?)
Only a PORTION of RBC broken down, causes biconcave disc –> SPHEROCYTE appearance
occurs in EXTRAVASCULAR HEMOLYSIS
IMHA using INTRAVASCULAR hemolysis (is it common? what happens? what do we often see on a bigger whole blood scale?)
LESS COMMON CAUSE OF IMHA
occurs when IgM (large antibody) binds to RBCs and causes HEMOLYSIS
often also see AGGLUTINATION
how can we test for IMHA? what does it do?
AUTO-AGGLUTINATION OR COOMB’S TEST
it tests for the ANTIBODY present on the RBC
4 causes of NON-regenerative anemia?
(1) iron deficiency
(2) chronic renal failure
(3) anemia of chronic disease
(4) bone marrow disease
chronic renal failure and non-regenerative anemia (causes, MCV/MCHC characteristics, lab findings INCLUDING USG)
can be caused by LACK OF FUNCTIONAL CORTICAL TISSUE or LACK OF FUNCTIONAL NEPHRONS
ALMOST ALWAYS NORMOCYTIC AND NORMOCHROMIC
lab findings
- AZOTEMIA = increase in nitrogenous waste products, BUN and creatinine
- LACK OF CONCENTRATING ABILITY = kidneys can’t concentrate, decreased USG
- ISOSTHENURIA = concentration of urine is no more than concentration of PLASMA
- USG findings?
–> Less than 1035 in cats
–> Less than 1030 in dogs
–> Less than 1025 in large animals
in pancytopenia, order of cells lost time-wise? how long do they usually live? where are they made?
NEUTROPHILS –> PLATELETS –> RBCs
Neutrophils = 12 hours
Platelets = 5-7 days
RBCs = 3-4 months
made in BONE MARROW
bone marrow disease and non-regenerative anemia (how is it diagnosed, MCV/MCHC characteristics, diseases and the most common disease that causes it, most important lab finding)
must be diagnosed through BONE MARROW EXAMINATION, not blood smear
ALMOST ALWAYS NORMOCHROMIC AND NORMOCYTIC
Diseases?
- lymphoma
- fibrosis
- infections
- MOST COMMON = INFILTRATING NEOPLASIA
Lab finding that’s most important?
- PANCYTOPENIA
erythroid hypoplasia (what it is, 2 main causes)
a type of NON-REGENERATIVE ANEMIA that targets RBC production in bone marrow
either idiopathic or immune-mediated
anemia of chronic disease (MCV and MCHC characteristics, how common it is, most common form/cause, lab findings that suspect, and what CONCURRENT lab findings would suspect)
ALMOST ALWAYS NORMOCYTIC AND NORMOCHROMIC
MOST COMMON TYPE OF NON-REGENERATIVE ANEMIA
USUALLY FROM INFLAMMATORY DISEASE; the body sequesters iron so that bacteria cannot get to iron and this causes lower RBC production
lab findings?
- NON-REGENERATIVE
- NORMOCYTIC
- NORMOCHROMIC
- NOT VERY SEVERE ANEMIA (greater than or equal to 23/24% in dogs/cats)
LOOK FOR INFLAMMATION, STRESS, OR SIGNS OF SYSTEMIC ILLNESSES
3+ blood in urine?
(1) RBCs –> CHECK SEDIMENT FOR RBCs
(2) Hb -
what do we expect if we suspect IMHA?
SPHEROCYTES
why might we see increased platelets? this is sort of random
INFLAMMATION
polycythemia definition
INCREASED PCV/HCT
AKA ERYTHROCYTOSIS
RELATIVE vs. ABSOLUTE polycythemia? (name 2 causes of each)
RELATIVE = APPEARS that there’s a PROPORTIONAL INCREASE IN RBCs, but really only due to…
(1) dehydration
(2) redistribution –> splenic contraction
ABSOLUTE = INCREASE in QUANTITY OF RBCs
(1) PRIMARY –> RARE, INCREASED production of RBCs from BONE MARROW due to NEOPLASTIC CELLS
(2) SECONDARY –> 2 TYPES
I. APPROPRIATE = increase in RBCs due to LOW O2 (chronic hypoxia)
–> High altitude
–> Chronic lung disease
–> Heart failure (R –> L shunt, CHF)
II. INAPPROPRIATE = RBCs made in response to EPO produced by the kidneys INAPPROPRIATELY
dehydration CBC/chem findings? what is the main finding that defines this?
RELATIVE CAUSE OF POLYCYTHEMIA/ERYTHROCYTOSIS
Increases of other values, such as…
(1) INCREASE IN TOTAL PROTEIN
–> Albumin and globulin proportionally increases
(2) INCREASE IN Na/Cl
–> Primary electrolytes in plasma
(3) INCREASE IN USG
–> This means URINE IS MORE CONCENTRATED
–> > 1.035 in cat, > 1.030 in dog, > 1.025 in LA
–> IF USG IS HIGHER THAN THESE VALUES, then the KIDNEY IS WORKING PROPERLY/concentrating urine
(4) +/- AZOTEMIA (increased BUN and creatinine)
–> Could be due to decreased blood flow being filtered by kidney
redistribution CBC/chem findings? what is the main finding that defines this?
RELATIVE CAUSE OF POLYCYTHEMIA
splenic CONTRACTION
(1) INCREASE RBCs
(2) INCREASE platelets
(3) INCREASE in mature neutrophils
–> Pushed off of walls/margination
(4) INCREASE in LYMPHOCYTES
(5) INCREASE in GLUCOSE
- Who does this happen to?
–> YOUNG ANIMALS
–> CATS
–> HORSES
–> **Cats, horses, and young animals are highly spirited and more likely to release epinephrine!
polycythemia vera definition & what animals it’s most common in
this is an example of ABSOLUTE polycythemia
PRIMARY = when bone marrow increases production of RBCs to make quantity of RBCs increase, NEOPLASM
COMMON IN OLDER ANIMALS, BUT RARE OVERALL
if we have erythrocytosis/polycythemia and NOTHING ELSE, then what is the likely cause?
DEHYDRATION
pre-renal azotemia causes? (3)
HYPOVOLEMIA
DEHYDRATION
GI BLEED (causes HIGH AMOUNTS OF RBC/PROTEIN TO BE BROKEN DOWN)
what animals are most likely to have PHYSIOLOGIC/REDISTRIBUTIVE reason for polycythemia/erythrocytosis? (3)
YOUNG ANIMALS
CATS
HORSES
THEY ALL FREAK OUT
where do platelets come from? (2 locations, and development)
BONE MARROW & SPLEEN
MegakaryoBLASTS –> MegakaryoCYTES
Megakaryocytes have PLATELETS IN CYTOPLASM, so once they are destroyed, BLEB OUT PLATELETS INTO CIRCULATION
how many platelets in spleen vs. circulation?
1/3 in spleen compared to blood
thrombopoeitin (where is it made, who binds it, what does it do)
made in bone marrow, liver, and spleen
bound up by megakaryocytes and platelets
when FREE (not a lot of platelets or megakaryocytes around to bind it), then PUSHES DEVELOPMENT OF MEGAKARYOCYTES to generate platelets
platelet enumeration (what machine does it, issues it can have, what we should do instead)
done automatically by a hematology analyzer on EDTA tube blood
machine will treat CLUMPS or LARGE PLATELETS as RBCs
we should do BLOOD SMEAR at 100X HIGH POWER field, multiply number found by 15-20,000
thrombocytopenia definition, normal range, mild, moderate, and severe
decrease in PLATELETS
NORMAL = 120,000 - 150,000
MILD = 80,000 - 120,000
MODERATE = <50,000
SEVERE = <25,000
what does moderate thrombocytopenia indicate vs. severe in terms of platelets or bleed being the primary cause?
MODERATE = BLEED IS THE PRIMARY CAUSE AND PLATELETS ARE BEING USED UP
SEVERE = DECREASED PLATELETS CAUSED THE BLEED
clinical signs of thrombocytopenia?
SURFACE BLEEDING (oozing of mucosal surfaces)
- GI
- Oral
- Bladder
PETECHIAE/ECCYMOSES
4 MAIN DIFFERENTIALS FOR THROMBOCYTOPENIA
(1) ARTIFACT
(2) CONSUMPTION
(3) PERIPHERAL DESTRUCTION
(4) DECREASED PRODUCTION
artifact in thrombocytopenia (what we see on smear, why it appears, and HOW we measure it/determine if it’s present)
CLUMPING OR LARGE PLATELETS
Hematology analyzer will count it incorrectly
MEASURE VIA PLATELET NUMBER x 15-20,000 and SEE IF IN NORMAL RANGE; ALSO ASSESS BLOOD SMEAR
consumption in thrombocytopenia (what kind of thrombocytopenia we expect, 3 diffs and CBC expectations)
associated with MILD to MODERATE thrombocytopenia
3 differentials
(1) BLEEDING EVENT
- MILD thrombocytopenia (bleeding first)
- LOW serum proteins
- PRE-REGENERATIVE/REGENERATIVE anemia
(2) DISSEMINATED INTRAVSCULAR COAGULATION (DIC)
- VARIABLE thrombocytopenia
- INCREASED PTT, +/- INCREASED PT
- Schistocytes (from RBC shearing)
- INCREASED D-Dimers
(3) VASCULITIS
- MILD thrombocytopenia
- INFLAMMATORY signs
peripheral destruction in thrombocytopenia, 2 differentials, 2nd differential has 4 subs
SEVERE, IMMUNE-MEDIATED THROMBOCYTOPENIA
- IDIOPATHIC
- SECONDARY to another disease…
(1) Infection (Rickettsial)
- Ehrlichia/anaplasma
- can still have NEGATIVE SNAP test because they can be in neutrophils/macrophages
- VARIABLE THROMBOCYTOPENIA
(2) Neoplasia
(3) Drugs
(4) Vaccines?
decreased production in thrombocytopenia, 2 differentials
due to BONE MARROW issue, uncommon
differentials –> DEPEND ON WHAT’S TARGETED
- Megakaryocytes TARGETED specifically, can’t make as many platelets
- WHOLE MARROW…
(1) Myelophthisis = marrow CAN’T MAKE MORE CELLS BC SOMETHING ELSE IS THERE (other cells, fibrosis)
(2) Hypoplasia = bone marrow just not making enough cells, so expect to see…
- Neutropenia
- Anemia
- Severe thrombocytopenia
thrombopathia basic definition
ABNORMAL platelet function
EXTRINSIC thrombopathia
caused by VON-WILLEBRAND FACTOR DEFECTS
vWF = helps platelets bind to subendothelial collagen to form platelet plug
CBC/chem findings
- NORMAL platelet numbers
- NORMAL PTT/PT
- ABNORMAL buccal mucosal bleeding time
- ABNORMAL platelet function assay
- ABNORMAL special vWF tests
molecular components inside of platelets (3)
- ALPHA granules
- DENSE granules
- TRANSMEMBRANE proteins
INTRINSIC thrombopathia (2 differentials, examples for second one)
CONGENITAL
- issues with GRANULE or TRANSMEMBRANE protein function INSIDE PLATELETS
- RARE
ACQUIRED
- from DISEASE or DRUGS
- DISEASE = RENAL FAILURE
- DRUGS = acetominophen
3 main things that would point us toward thrombopathia?
- BLEEDING with NO INDICATORS OF TRAUMA
- NORMAL SECONDARY HEMOSTASIS (not mediated by platelets)
- EVIDENCE OF PLATELET ABNORMAL FUNCTION (vWF test, buccal mucosal bleeding time, etc.)
Thrombocytosis (3 differentials)
= INCREASE in number of platelets
- REACTIVE
- from diseases involving INFLAMMATION
- from CHRONIC EXTERNAL BLOOD LOSS (release EPO, resembles thrombopoietin)
- Ex = IRON DEFICIENCY ANEMIA
–> can cause IL-6 and EPO release, mimicking THROMBOPOIETIN and causing increase
–> On CBC/chem, look for DECREASED MCV/MCHC and SIGNS OF CHRONIC INFLAMMATION - REDISTRIBUTION
- Ex = SPLENIC CONTRACTION secondary to EPINEPHRINE RELEASE
–> Neutrophilia
–> Lymphocytosis
–> Thrombocytosis
–> Polycythemia
–> Increase in blood glucose - CANCER
- platelets become neoplastic, RARE
3 things that secondary hemostasis depends on?
(1) Vessels/integrity
(2) Platelets
(3) Clotting factors
clotting factors (where they’re made, what they work alongside of, function, what’s needed for them to work properly)
made by the LIVER
work alongside PLATELETS
help to form fibrinogen –> fibrin CLOT, make it NON-SOLUBLE
need adequate AMOUNT and NORMALLY FUNCTIONING clotting factors
what clotting factors are in the intrinsic pathway? how is it tested WITH THE COMMON PATHWAY?
12, 11, 9, 8
PTT/ACT
what clotting factors are in the extrinsic pathway? how is it tested WITH THE COMMON PATHWAY?
tissue factor (TF), 7
PT
what clotting factors are in the common pathway?
10, 5, 2
vitamin-K activated clotting factors (4)
2, 7, 9, 10
clotting disorders and hypocalcemic animals?
HYPOCALCEMIC ANIMALS WILL NOT HAVE CLOTTING DISORDERS
Ca is only a co-factor for clotting
coagulation tests are generally ___
INSENSITIVE, we need a big loss of clotting factors to show PROLONGATION
PTT increase?
caused by >75% loss in INTRINSIC/COMMON PATHWAY factors
12, 11, 9, 8, 10, 5, 2
PT increase?
caused by >75% loss in EXTRINSIC/COMMON PATHWAY factors
TF, 7, 10, 5, 2
TT (thrombin time) increase?
DISSEMINATED INTRAVASCULAR COAGULOPATHY or issue with fibrinogen
3 differentials for RED urine dipstick?
(1) RBCs
(2) Hb
(3) Myoglobin
Hb and Myoglobin will NOT clear with ___
Sedimentation
measurement of FIBRINOGEN in relation to CLOTTING?
Fibrinogen = clotting factor
Can either do a PRECIPITATE (precipitates fibrinogen out of blood) or AUTOMATED**
ACT increase? (there’s an extra reason for increase here, and difference between this test and other clotting tests)
> 95% of INTRINSIC or COMMON PATHWAY factors GONE to see ELEVATION
TF, 7, 10, 5, 2
ALSO INCREASED IF PLATELET NUMBER IS LESS THAN 10,000
Done MANUALLY, gray-top tube that’s checked every 5 mins for clotting; diatomaceous earth inside tube!
INCREASED PTT & NORMAL PT?
**STILL NEED >75% FACTORS GONE TO SEE ELEVATION
ABNORMAL INTRINSIC (12, 11, 9, 8)
12 = deficiency in cats seen, NO BLEED/NOT CLINICALLY SIGNIFICANT
11 = RARE, in some Holsteins/dogs
8/9 = COMMON, hemophilia A (8) and B (9)
–> 8 more common
–> Often X-linked and congenital (more common in young males)
–> we could do FACTOR LEVELS to determine which one it is
ACT INCREASED but NORMAL PTT? (weird one)
PLATELET COUNT LESS THAN 10,000, REGARDLESS IF SECONDARY COAGULATION FACTORS ARE NORMAL OR NOT
PT INCREASED but NORMAL PTT?
likely JUST EXTRINSIC PATHWAY ABNORMAL
TF and 7
Factor 7 deficiency more common, no real problems in TF
(1) INHERITED in beagles
(2) ACQUIRED** MORE COMMON
–> VITAMIN K ANTAGONISM, think of RODENTICIDES!
–> Factor 7 has the shortest half-life and is vitamin K-dependent
BOTH PTT and PT INCREASED? (what can’t it be, 3 differentials w/ CBC inclusions in one particular organ-related differential)
cannot be INHERITED because we can’t have MULTIPLE FACTORS involved
(1) VITAMIN K ANTAGONISM/RODENTICIDE
- affects vitamin K-dependent factors (2, 7, 9, 10), which are in BOTH INTRINSIC AND EXTRINSIC PATHWAY
(2) LIVER FAILURE
- liver makes clotting factors
- also see DECREASE in things that liver is responsible for… (ABC GLUCOSE)
–> ALBUMIN
–> BUN
–> CHOLESTEROL
–> GLUCOSE
(3) DISSEMINATED INTRAVASCULAR COAGULOPATHY
- CLOTTING SYSTEM IS OVERACTIVE/UNREGULATED
- expect to see…
–> increased PT/PTT
–> SCHISTOCYTES (sheared RBCs) from clots shearing them
–> D-Dimers (clots broken down)
–> Thrombocytopenia (mild to severe) due to CONSUMPTION to MAKE CLOTS
thrombin function & what clotting factor it is
converts FIBRINOGEN –> FIBRIN
THIS IS CLOTTING FACTOR 2 (common pathway)
what should we be looking at when searching for DIC? (6)
+/- CBC/chem = signs of INFLAMMATION
Blood smear = SCHISTOCYTES
Platelets = THROMBOCYTOPENIA, using up platelets for clots
DECREASED fibrinogen
INCREASED D-DIMERS
DECREASED antithrombin
DIC (why it’s “death in cage,” what it causes pathophys)
“death in cage”
Causes such severe ISSUES WITH CLOTTING that POOR PERFUSION –> CELL DEATH –> ORGAN DEATH
Causes?
UNREGULATED MAKING AND BREAKING OF CLOTS
protein-losing nephropathy vs. enteropathy?
expect to see BOTH ALBUMIN AND GLOBULIN lost in ENTEROPATHY but NOT NEPHROPATHY
This is because bigger “holes” for globulin, then larger protein
IMHA can sometimes cause INCREASED LIKELIHOOD OF ___, so we might expect to see increased ____
clotting!
D-Dimers
keratocytes, acanthocytes, and schistocytes DDxs?
(1) iron deficiency anemia
(2) DIC
(3) hemangiosarcoma
(4) Glomerulonephritis
(5) Heart disease
(6) Microangiopathy (capillaries become thick and weak and bleed out contents)
