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Clin Path Exam II
Platelets through electrolytes
156
Veterinary Medicine
Graduate
10/31/2014

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Term
Major events in hemostasis:
Definition
formation of primary platelet plug

formation of insoluble crosslinked fibrin

clot retraction and fibrinolysis
Term
Main components of hemostasis
Definition
blood vessels
platelets
coagulation system
Term
Key functions of blood vessels in hemostasis:
Definition
structural framework for hemostasis (interxns with platelets and coag factors)
neuromechanical (vasoconstriction)
biochemical (endothelial synthesis and metabolism of key regulatory molecules)
Term
What does the coagulation system aim to achieve?
Definition
rapid formation of insoluble fibrin clot
eventual elimination of clot
prevention of inappropriate clotting during normal hemostasis
Term
What enzyme is formed in the coagulation cascade that converts fibrinogen to fibrin?
Definition
Thrombin
Term
Intrinsic, extrinsic and common pathways part of:
Definition
coagulation cascade
Term
Which pathways provide checks and balances to the coagulation process and are activated simultaneously with coag cascade:
Definition
anticoagulant and fibrinolytic pathways
Term
What chemical are platelets mainly regulated by?
Definition
TPO
Term
Lifespan of platelets
Definition
1 week
Term
How does the structure of platelets change?
Definition
When quiescent, they are flat and discoid; when activated spherical with pseudopodia
Term
Platelets have a dense tubular system that is a reservoir for....
Definition
Ca
Term
Platelet granules contain (6):
Definition
histamine
VWF
serotonin
calcium
ADP
fibrinogen
Term
What maintains platelet shape, mediate shape change, and release of granule contents:
Definition
cytoskeletal componenets
Term
Surface receptor for fibrinogen? and for VWF?
Definition
GPIIb-IIIa; GPIb
Term
Soluble agonist that activates platelets? insoluble?
Definition
thrombin; collagen
Term
Mahor function of platelets in hemostasis:
Definition
1. adhesion to damaged vessel and aggregation
2. release of granule substances & TXA2
3. clot retraction
Term
Good venipuncture techniques:
Definition
avoid activating platelets (false positives!)
Term
Which two tubes are used to collect blood: which is routine and which is for specialized tests:
Definition
EDTA (purple top); sodium citrate (light blue)
Term
Which platelet tests are part of the routine CBC?
Definition
platelet concentration
MPV
Term
estimated number of platelets from smear=
Definition
[avg #/HPF (100x)] x (20,000)
Term
MPV tends to increase if what increases?
Definition
thrombopoiesis
Term
What four things do you evaluate with platelet morphology?
Definition
size
shape
granularity
verification of automated
Term
What will falsely decrease platelet count?
Definition
clumping (esp in cats)
Term
When do we use a bone marrow aspirate to evaluate platelets?
Definition
assess thrombopoiesis, esp with unexplained thrombocytopenia
Term
Decreased platelet production = decreased ____________
Definition
megakaryocytes
Term
^ platelet destruction = ^ ___________
Definition
megakaryocytes
Term
What test do we use to evaluate immune mediated platelet disease?
Definition
Flow cytometry
Term
If you have a bleeding problem and have NORMAL PLATELET #'s and NORMAL PT, PTT, what do you do next?
Definition
BMBT
Term
What does BMBT assess?
Definition
platelet plug formation by measuring time interval between injury and cessation of bleeding
Term
What might prolonged time on BMBT imply?
Definition
- defect in 1 or 2 platelet function
-VWB disease
-vascular lesion/defect
- decreased number of platelets
Term
What sort of sensitivity does BMBT have?
Definition
LOW
Term
When is BMBT contraindicated?
Definition
if pt is thrombocytopenic
Term
What are some specialized tests we can use to evaluate platelet disorders?
Definition
-aggergometry
-flow cytometry
-thromboeslastography
-PFA-100
-clot retraction test
Term
Three things important in evaluating suspected bleeding disorders:
Definition
signalment
history
clinical signs
Term
What characteristics are important in distinguishing acquired vs hereditary platelet diseases:
Definition
age, breed, sex
Term
What might you ask about when taking a history for platelet disorders:
Definition
trauma, rodenticide, family history of bleeding
Term
Primary hemostasis results in _____ bleeds
Definition
small (petechiae, ecchymosis, after venipuncture)
Term
Secondary hemostatis results in _____bleeds
Definition
big (hemorrhage into body cavities and joints, large hematomas, delayed bleeding after venipuncture)
Term
Mechanisms of thrombocytopenia:
Definition
1. increased destruction of platelets (IMT)
2. Increased consumption (DIC)
3. Decreased production (Immune-mediated destruction, myelotoxicity, infection)
4. Abnormal distribution (splenomegaly, endotoxemia)
5. Hemorrhage (does not result in thrombopenial alone)
6. Dilution
Term
Which breed often has macrothrombocytopenia?
Definition
Cavaliers
Term
Mechanisms of thrombocytosis?
Definition
1. Reactive (inflammation, iron deficiency)
2. Regenerative (recovery from thrombocytopenia)
3. Decreased sequestration (splenic contraction)
4. Essential thrombocythemia (form of chronic leukemia)
Term
Platelet function disorders:
Definition
1. Primary-intrinsic inherited/congenital platelet defect (GLANZMANN's thromboasthenia- absent or markedly decreased expression of fibrinogen receptor)
2. Secondary (aquired)- IMT, hyperglobulinemia, uremia, drugs, increased fibrinolytic products in plasma
3. VWF disease- deficiency of VWF technically not a platelet disorder.
Term
Type 1 VWF disease-
Definition
partial quantitative deficiency (<50%) variable bleeding tendency
Term
Type II VWF disease-
Definition
qualitative abnormalities-moderate to severe bleeding tendency
Term
Type III VWF disease-
Definition
severe quantitative deficiency- (<0.1%) severe bleeding tendency
Term
VWF disease lab findings (5)
Definition
normal platelet count
prolonged bleeding time
PTT ACT normal
PT normal
secialized laboratory tests
Term
Pathogenesis of bleeding associated with vascular disorders-
Definition
failure to support collagen-platelet interactions and adhesion initiating hemostasis
Term
Isosthenuria
Definition
USG of 1.007- 1.013 (glomerular filtrate was unaltered by tubules
Term
Hypersthenuria
Definition
Excretion of highly concentrated urine
Term
Hyposthenuria
Definition
UDG of < 1.007 (evident tubular dilution)
Term
Routine laboratory evaluation of rental function includes:
Definition
Plasma biochem analysis (esp BUN and creatinine)
And urinalysis (esp USG)
Term
Increased BUN:
Definition
Decreased GFR;
High protein diet or upper GI bleeding
Term
Decreased BUN:
Definition
Hepatic insufficiency (no synthesis of urea)
Increased renal excretion (overhydration, DI)
Low protein diet or malabsorption
GI utilization of urea (microbes)
Term
Increased creatinine:
Definition
Decreased GFR
Increased muscle mass
Term
Decreased creatinine
Definition
Severe muscle wasting
Term
What is the reference interval for USG?
Definition
There is not one, as it depends of species and hydration state
Term
What must USG always be interpreting in light of?
Definition
Hydration status
Urine output
Term
First things to do when diagnosing a bleeding pt:
Definition
Good history and localize the lesion!
Term
To make a clot in the body, you need the following things: (5)
Definition
Phospholipids
Calcium
Clotting factors
Functional endothelium
vWF
Term
BMBT test:
Definition
-Small, standardized incision initiates hemostasis
-BMBT is the time in seconds that it takes from making the incision to stopping bleeding
-prolonged BMBT suggests PLATELET FUNCTION DEFECT, though not specifically which one
-commonly used to screen for vWF disease
Term
ACT (Activated clotting time)
Definition
-uses fresh whole blood
-diatomaceous earth is the contact activator
-ACT is the time in seconds from placing the blood in tube until clot formation
-prolonged ACT suggests a defect in the INTRINSIC or COMMON pathways
-should go on after this for further coagulation testing
-used for cage side testing in ER
Term
These tests evaluate soluble clotting factors:
Definition
Partial thromboplastin time (PTT) and Prothrombin time (PT)
Term
PTT (partial thromboplastin time)
Definition
-citrate-anticoagulated plasma
-only measure SOLUBLE CLOTTING FACTORS dissolved in plasma
-pronged PTT suggests a defect in the INTRINSIC or COMMON pathways
-PTT it the time in seconds from addition of calcium to clot formation
-phospholipids added as reagent
-part of routine coagulation panel
Term
PT (prothrombin time)
Definition
-citrate-anticoagulated plasma
-only measures the activity of SOLUBLE CLOTTING FACTORS dissolved in the plasma
-phospholipids + TF added as a reagent
-PT is the time in seconds from the addition of reagents to clot formation
-prolonged PT suggests a defect in the EXTRINSIC or COMMON pathway
-part of routine coagulation panel
Term
Best testing for assessing hypercoagulability in vet patients
Definition
TEG-ROTEM
Term
Thrombin time (TT)
Definition
-citrate sample
-measures the activity of FIBRINOGEN dissolved in the plasma
-TT is the time in seconds from addition of thrombin to clot formation
-Prolonged TT suggests problem with fibrinogen (hypo or abnormal fnxn)
-performed when fibrinogen problem is suspected
Term
What tests can heparin contamination cause a prolongation of results in?
Definition
ACT, PTT TT
Term
Fibrinogen concentration (TT Clause)
Definition
-citrate sample
-commonly used for evaluation for DIC
Term
Antithrombin (AT)
Definition
-citrate sample
-amount of antithrombin (active) is measured
-Decreased AT activity can be due to decreased AT production (liver d'se), loss or consumption
Term
FDP's testing
Definition
-biomarker of clotting/fibrinolysis
-citrate sample
-amount of fibrinogen degradation product is measured
- ^ FDP suggests fibrinolysis (associated with DIC, decreased clearance of FDPs from the body (liver, renal d'se)
Term
D-dimer test
Definition
-no kit on the market
-citrate sample
-amount of D-dimer in plasma measured
-the higher the D-dimer measured the more specific it is for thrombosis
Term
Which clotting factors are vitamin K dependent?
Definition
2, 7, 9, 10
Term
Which clotting factors are the common pathway?
Definition
(from top to bottom) 10, 5, 2, 1
Term
Clotting factors are in the intrinsic pathway?
Definition
(from top to bottom) 12, 11, 9, 8
Term
Clotting factors in extrinsic pathway?
Definition
(top to bottom) TF, 7
Term
What are 4 differentials for concurrently increased PT and PTT?
Definition
1. vit K antagonism/absence
2. Liver failure
3. DIC
4. common pathway factor defect (hypo/dysfibrinogenemia)
Term
Immune-mediated thrombocytopenia lesion localization?
Definition
Platelet numbers problem
Term
vWF disease lesion localization:
Definition
Reduced vWF (normal platelets, though)
Term
Hemophilia lesion localization
Definition
Intrinsic pathway problem (absent clotting factors 8 or 9
Term
BMBT test:
Definition
-Small, standardized incision initiates hemostasis
-BMBT is the time in seconds that it takes from making the incision to stopping bleeding
-prolonged BMBT suggests PLATELET FUNCTION DEFECT, though not specifically which one
-commonly used to screen for vWF disease
Term
ACT (Activated clotting time)
Definition
-uses fresh whole blood
-diatomaceous earth is the contact activator
-ACT is the time in seconds from placing the blood in tube until clot formation
-prolonged ACT suggests a defect in the INTRINSIC or COMMON pathways
-should go on after this for further coagulation testing
-used for cage side testing in ER
Term
These tests evaluate soluble clotting factors:
Definition
Partial thromboplastin time (PTT) and Prothrombin time (PT)
Term
PTT (partial thromboplastin time)
Definition
-citrate-anticoagulated plasma
-only measure SOLUBLE CLOTTING FACTORS dissolved in plasma
-pronged PTT suggests a defect in the INTRINSIC or COMMON pathways
-PTT it the time in seconds from addition of calcium to clot formation
-phospholipids added as reagent
-part of routine coagulation panel
Term
PT (prothrombin time)
Definition
-citrate-anticoagulated plasma
-only measures the activity of SOLUBLE CLOTTING FACTORS dissolved in the plasma
-phospholipids + TF added as a reagent
-PT is the time in seconds from the addition of reagents to clot formation
-prolonged PT suggests a defect in the EXTRINSIC or COMMON pathway
-part of routine coagulation panel
Term
Best testing for assessing hypercoagulability in vet patients
Definition
TEG-ROTEM
Term
Thrombin time (TT)
Definition
-citrate sample
-measures the activity of FIBRINOGEN dissolved in the plasma
-TT is the time in seconds from addition of thrombin to clot formation
-Prolonged TT suggests problem with fibrinogen (hypo or abnormal fnxn)
-performed when fibrinogen problem is suspected
Term
What tests can heparin contamination cause a prolongation of results in?
Definition
ACT, PTT TT
Term
Fibrinogen concentration (TT Clause)
Definition
-citrate sample
-commonly used for evaluation for DIC
Term
Antithrombin (AT)
Definition
-citrate sample
-amount of antithrombin (active) is measured
-Decreased AT activity can be due to decreased AT production (liver d'se), loss or consumption
Term
FDP's testing
Definition
-biomarker of clotting/fibrinolysis
-citrate sample
-amount of fibrinogen degradation product is measured
- ^ FDP suggests fibrinolysis (associated with DIC, decreased clearance of FDPs from the body (liver, renal d'se)
Term
D-dimer test
Definition
-no kit on the market
-citrate sample
-amount of D-dimer in plasma measured
-the higher the D-dimer measured the more specific it is for thrombosis
Term
Which clotting factors are vitamin K dependent?
Definition
2, 7, 9, 10
Term
Which clotting factors are the common pathway?
Definition
(from top to bottom) 10, 5, 2, 1
Term
Clotting factors are in the intrinsic pathway?
Definition
(from top to bottom) 12, 11, 9, 8
Term
Clotting factors in extrinsic pathway?
Definition
(top to bottom) TF, 7
Term
What are 4 differentials for concurrently increased PT and PTT?
Definition
1. vit K antagonism/absence
2. Liver failure
3. DIC
4. common pathway factor defect (hypo/dysfibrinogenemia)
Term
Immune-mediated thrombocytopenia lesion localization?
Definition
Platelet numbers problem
Term
vWF disease lesion localization:
Definition
Reduced vWF (normal platelets, though)
Term
Hemophilia lesion localization
Definition
Intrinsic pathway problem (absent clotting factors 8 or 9
Term
What are the three markers of hepatocellular injury?
Definition
ALT (sensitive marker, but also indicates muscle damage)
AST (less sensitive and specific marker for hc injury)
SDH (highly specific for hc injury in birds, horses)
Term
Rule outs for increased AST
Definition
1. hc injury
2. Muscle damage
3. RBC lysis
Term
Rule outs for increased ALT
Definition
1. hc damage
2. hc regeneration
3. induction by some drugs
4. Muscle damage
Term
Markers of cholestasis:
Definition
-ALP
-GGT (biliary hyperplasia)
-Cholesterol (increased synthesis and decreased excretion from hepatocytes)
-Bilirubin (increased RBC breakdown, lesion inhibiting bile flow through canaliculi---ducts)
Term
Markers fro impairs liver function:
Definition
Bilirubin increased (though Fry takes it back)
Albumin decreased
Cholesterol decreased
Glucose decreased
Urea decreased
Term
Why is ammonia increased while urea is decreased during impaired hepatobiliary disease?
Definition
Because functional impairment of the liver prevent the urea cycle from converting ammonia to urea
Term
Which analyze is the marker for muscle disease?
Definition
Creatine kinase
Term
Pre-renal azotemia
Definition
Secondary o Hypovolemia and reduced renal blood flow caused by dehydration, hv shock, or decreased CO
Term
In pre-renal azotemia you'd expect to find ____________ urine, which varies by species
Definition
Fully concentrated/hypersthenuric
Dog >1.030
Cat >1.040
Horses and cattle >1.025
Term
Renal azotemia
Definition
Secondary to renal disease that causes a significant decrease in GFR/renal function
Term
In renal azotemia, you'd expect to find azotemia with ________to _____ urine concentration
Definition
Little to no (so very dilute)
Term
Post-renal azotemia
Definition
Caused by urinary tract obstruction or rupture (obstruction results in back pressure and impaired glomerular filtration and rupture leads to reabsorption of urea and creatinine from peritoneal cavity)
Term
With post renal azotemia, what laboratory finding can we expect to find?
Definition
Azotemia with variable USG; hyperkalemia; +/- abdominal effusion
Term
What two analytes are the best to measure when trying to diagnose uroabdomen
Definition
Creatinine and potassium
Term
Complete urinalysis consists of:
Definition
1. Physical inspection
2. USG
3. Biochemical dipstick analysis
4. Miscroscopy
Term
Physical inspection of urine includes:
Definition
Color
Clarity
Odor
Term
When do we see glucosuria?
Definition
when the renal tubular restoration threshold is overwhelmed due to hyperglycemia- causes osmotic diuresis and decreased concentrating ability will result in increase in volume)
Term
T/F trace to mild bilirubinemia is within normal limits in dogs (1+ to 2+)
Definition
True
Term
T/F some ketones are normal findings healthy animals
Definition
False - positive ketones results are always pathologic as it represents a shift in energy production from using carbohydrates to lipids
Term
Specific gravity is reliable in animals on a dipstick (t/f)
Definition
false
Term
Blood dipstick pad is insensitive (t/f)
Definition
False- it is very sensitive
Term
PH is reliable/unreliable in animals with a dipstick pad?
Definition
unreliable
Term
When analyzing the protein in a urine sample, what is the best method of doing so?
Definition
Protein: creatinine ratio (both values are done by automatic analyzer)
Term
Urobilinogen, nitrites, and leukocytes on dipstick UA:
Definition
Unreliable- DO NTO USE
Term
Persistent proteinuria:
Definition
Proteinuria occurring on 3 or more urine samples taken at least two weeks apart from each other
Term
Microscopic evaluation of urine:
What are we looking for at 40x?
At 100x?
Definition
Casts (40)
Cells, crystals, microorganisms (100)
Term
When is bacteria in a urine sample significant?
Definition
When it was obtained sterilely
Term
What is the number or normal RBCs/WBCs per high powered frame?
Definition
0-5
Term
Rare casts of this kind are considered normal?
Definition
Headline and granular
Term
Laboratory hallmarks of ACUTE RENAL FAILURE
Definition
-moderate to marked azotemia that developed within days
-little to no urine production
-moderate to complete loss of concentrating ability
-hyperkalemia
-not anemic
Term
Laboratory hallmarks of CHRONIC RENAL FAILIURE
Definition
-non regenerative anemia
-mild to marked azotemia that progresses over time
-hypokalemia
-mild to complete loss of concentrating ability
-polyuric until end stage, then anuric
Term
Laboratory hallmarks of glomerulonephritis:
Definition
-proteinuria
-hypoalbuminemia
-inactive urine sediment
Term
Pyelonephritis laboratory hallmarks:
Definition
-clinically sick animal
-pyuria, hematuria, bacteriuria, +/- cylindruria, +/- reduced USG
-azotemia?
-inflammatory leukogram?
Term
Laboratory hallmarks of cystitis:
Definition
-pyuria
-hematuria
-bacteriuria
Term
The electrolytes we measure on routine chemistries represent what is happening in which fluid compartment
Definition
ECF
Term
Four factors affect electrolyte concentrations in the body:
Definition
Oral intake
Shifts between ICF and ECF
Excretion or loss of electrolytes
Acid-base balance
Term
What other info must you know to interpret sodium?
Definition
Hydration status
ECF volume
Term
What other info must you know to interpret chloride?
Definition
Na concentration
Hydration status
bicarb concentration
Acid-base status
Term
What other info must you know to interpret potassium?
Definition
Acid-base status
Urine output
Term
What are the two major mechanisms by which Na is controlled in the body?
Definition
1. Control of blood volume (Baroreceptors in kidney, atria, carotid sinus)
2. Regulation of plasma osmolality (osmoreceptors in hypothalamus)
Term
SODIUM IS A MAJOR DETERMINANT OF EFFECTIVE PLASMA OSMOLALITY
Definition
Just know this
Term
Why can changes to plama/serum concentration of Na be relative or absolute?
Definition
Na concentration depends on the ratio of total body Na to total body water
Term
Plasma chloride is regulated by these two mechanisms:
Definition
1. Renal excretion and absorption
2. GI tract secretion
Term
Chloride often changes in parallel with what electrolyte?
Definition
Na
Term
What two things are chloride concentration influenced by?
Definition
Acid-base status
Bicarbonate changes
Term
If chloride is abnormal, what is the first thing you should do?
Definition
Look at sodium
Term
If Na and CL are not changing in parallel, what should you look at next?
Definition
TCO2 (bicarb measure)
Term
If chloride is low and TCO2 is HIGH?
Definition
Metabolic alkalosis --> GI loss of chloride
Term
If chloride is low and TCO2 is LOW?
Definition
Metabolic acidosis --> GI loss of bicarb likely
Term
If chloride is HIGH and TCO2 is low?
Definition
Metabolic acidosis -->if anion gap is normal, then it is RENAL TUBULAR ACIDOSIS
Term
What electrolyte characteristics define renal tubular acidosis?
Definition
Normal anion gap, high chloride, low bicarb
Term
Hypochloremic metabolic alkalosis- what disease process should ring a bell?
Definition
Loss/sequestration of gastric acid
(pylori outflow obstruction or displaced abomasum)
Term
Plasma K concentration is regulated by these mechanisms:
Definition
1. Distribution between ECF and ICF by ATPase cell membrane pump
2. Renal excretion
Term
POTASSIUM IS TIGHTLY REGULATED BC TOO MUCH IS DANGEROUS
Definition
KNOW IT
Term
Why is urine not being made dangerous in regard to K?
Definition
Because renal excretion is an important mechanism of getting rid of K
Term
Why is hyperkalemia life-threatening?
Definition
It leads to muscles weakness, arrhythmias, and cardiac arrest
Term
3 Rule outs for azotemia with hyperkalemia:
Definition
1. Urinary tract obstruction or rupture
2. oliguric or anuric renal failure
3. Hypoadrenocorticism
4. Exceptional rhabdomyalisis/tumor lysis syndrome
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