Blood transfusions, fluid therapy, SIRS. Ch 2-4 Flashcards
Clinical indications for blood transfusion (4)
PCV <20% (remembering PCV may not fall until at least 12hrs)
Estimated 30% or more blood loss
Oxygen extraction ratio >50%
Lactate >4mmol/L
Equine blood volume
8% bodyweight ie 40L in a 500kg horse
Blood donation volume
Maximum 20% of blood volume (ie 8L in 500kg horse)
Replacement IVFT is recommended if >15% blood volume taken
Blood transfusion equation based on PVC
Transfusion volume (L) = bodywt x 0.08 x (desired PCV-actual PVC)
donor PCV
Equation to calculate amount of plasma to be transfused
Bwt x 0.045 x (desired TP - actual TP)
donor TP
Same as for blood transfusion except times by 0.045 vs 0.08 (blood volume vs plasma volume)
Oxygen extraction ratio
O2 ER = PaO2 - PVO2
PaO2
Transfusion required at >50% - ie if venous blood is very deoxygenated
Ideal blood donor
Large gelding with no previous blood transfusion
Negative for Aa and Qa alloantigens - these are the two most likely associated with transfusion reactions
Red blood cell half life of allogenic and autogenous red cells collected 24hr previously
20 days allogenic
45 days autogenous
Major crossmatch
Detects agglutination between donor red cells and recipient serum
Minor crossmatch
Detects agglutination between donor serum and recipients red cells
Blood storage times
Can store whole blood in CPDA-1 for 28days (says upto 21d in a fridge at 1-6’C in Slatter)
Packed red cells for 35d (not recommended in humans - higher mortality vs whole blood)
(Says 21d in Slatter with CPDA-1 and longer if red cell additive used)
FFP - upto 1 year at -18’C. Upto 3 months in normal household freezer
FP - 4 years
Distribution of total body water
60% of body weight
66% intracellular
33% extracellular
ECF divided into interstitial (75%) and intravascular (25%)
IV fluid compartment is the smallest
Difference between fresh frozen plasma and frozen plasma
FFP is plasma separated and frozen at -18’C within 8 hours of collection
FP is either FFP after 1 year of frozen storage (it is then useable as FP for 4 years at -18) or blood that has been separated and stored >8hours after collection
Frozen plasma products maintain factors II, VII, IX and X (also the vit K dependent factors) and albumin and Igs. BUT LACK factors V, VIII and von Willebrand factor
Administration of packed red cells
Last refrigerated at least 21 days with CPDA-1
Ideally leave with some plasma such that PCV <80%. Agitate daily
To administer, resuspend with 0.9%NaCl. Calcium containing fluids incl Hartmanns should NOT be used - can cause coagulation
(says 10ml saline per 30-40ml red cells in slatter)
Components of primary haemostasis
Local vasoconstricton
vWF factor release from endothelial cells (Weibel-Pallade bodies)
Platelet attraction, activation and adhesion (the 3 a’s)
The interaction of activated platelets with the exposed subendothelium of blood vessels is the basis of primary hemostasis
Role of platelets in secondary haemostasis
Once activated, they undergo conformational change exposing binding sites for specific coagulation factors
How is platelet adhesion mediated
Through expression of P-selectin on activated (damaged) vascular endothelium and through the platelet receptor GPIbα, which attaches to vWF
Definition of SIRS
Inappropriate generalised inflammatory response to tissue damage/infection w mechanisms intended to defend & repair; but exaggerated systemic reaction rx in clinical state of SIRS - can be more detrimental than the initial insut itself
List 5 pro-inflammatoy cytokines
IL-1
IL-6
IL-8
TNF-∝
IFN-𝛾
List 5 (predominantly) anti-inflammatory cytokines (NB some X-over in pro/anti-inflammatory function)
IL-4
IL-10
IL-11
IL-13
TGF-β
Briefly describe the arachadonic acid cascade
- AA rx from membrane phosopholipid through the action of PLA2
- AA is metabolised via COX and LOX pathways to generate eicosanoids
- Eicosanoids comprise leucotrines (LOX) and prostanoids (COX) = prostaglangins and thromboxane A2
What are the 2 main acute phase proteins in horses?
SAA
C-reactive protein (role in complement activation)
Colletively responsible for many of the effects incl pyrexia, anorexia and depression
Synthesised in the liver; ↑in response to IL-1,6 & TNF
Briefly describe the complement system
Functions to enhance immune defense (phagocytosis and antibody function) against pathogens. Part of the innate immune system but can be stimulated by the adaptve (AG-AB complexes)
Several inactive protein precursors (synthesised in the liver); when activated they induce bacteriolysis, ↑vascular permeability, ↑neut chemotaxis & ↑opsonisation (susceptibility to phagocytosis) of microbes and damaged cells
List the diagnostic criteria for SIRS in adults (3)
- Rectal temp: >38.5°C of <37°C
- HR >52bpm
- WBC count: >12.5 or <5x109/L, or >10% bands
Addition of lactate >2.06mmol/L and abnormal mm colour may be useful
Can make a dx when 2 or more are satisfied
Key considerations in sepsis scoring for neonates
Scoring of 0-4 for 14 parameters
HISTORY - 1. placentitis? Y=3/N=0
- Gestation length - <300=3, 300-310=2, 311-330=1 >330=0
PE: 3. Petechiae/scleral injection
- Fever -
- Hypotonia, coma, seizure - Marked=2, mild=1
- Anterior uv, d+, ARDS, joint effusions - Y=3, N=0
LAB: 7. Neuts - <2=3, 2-4 or >12=2, 8-12=1
- Band neuts/µL - >200=3, 50-200=2
- Toxic neuts - Marked=4, mod=3, mild=2, none=0
- Fib - >600=2, 4-600 =1, <400=0
- Glucose - <50=2, 50-80=1, >80=0
- IgG - <200=4, 2-400 =3, 4-800=3, >800=0
- PaO2 - <40=3, 40-50=2, 50-70=1, >70=0
- Metabolic acidosis - Y=1, N=0
TOTAL SCORE ≥11 IS PREDICTIVE OF SEPSIS (or use cutoff of 12 if PaO2 and metabolic acidosis are included)
Definition of MODS
Altered organ function in acutely ill patient such that homeostasis cannot be maintained
Diagnostic criteria for MODS
No equine consensus. Various human scoring systems, none really validated in EQ other than 1 in surgical colics only (JVIM 2016) - score >8 on d1 and >6 on d2 assoc w nonsurvival
Looks at lab parameters from 8 organ/systems
Obel laminitis grading
Graded 0-4 (0=normal)
1 - Normal walk, stilted trot but no obv head not
2 - Stilted walk, obv lameness at trot but can easily lift limbs
3 - Lameness obvious at walk, reluctant to lift limb(s)
4 - Marked lameness, difficulty weight bearing and reluctant to move
What is the main mechanism of innate immunity
- Via pattern recognition receptors (PRRs) which detect pathogen associated molecular patterns (PAMPs); evolutionary conserved molecules unique to microbes, usually essential for their survival/virulence
- 3 main types of mammalian PRRs incl 1) secreted PRRs, incl defensins; (2) cell membrane PRRs involved in phagocytosis; and (3) cell membrane PRRs involved in signal transduction
- PAMPs incl bacterial cell wall extracts (LPS), peptidoglycan, prokaryotic DNA
Structure of endotoxin
3 main domains
- Lipid A
- Core polysaccharide
- O antigen
Variation in no/length of FAs on glucosamine disaccharide backbone of lipid A confers degree of toxicity
What is the main source of endotoxin
Large pool of GRAM NEGATIVE gut bacteria - LPS is major component of their outer membrane.
Endotoxin must gain access to circulation to exert toxic effect
Cellular steps in pathophysiology of endotoxaemia
- Lipopolysaccharide binding protein (LBP) (acute phase protein) binds LPS & extracts it from aggregated micelles in the blood - transport to various sites which determines host response in large part - [LBP] can ↑>100fold in 24hr
- Can be transported to the cell surface of host inflammatory cells to evoke inflamm response or can be transferred to other neutralising lipoproteins, such as high-density lipoprotein, for eventual removal from the blood
- Once at the cell surface, LPS is transferred to CD14, expressed by monocytes/macrophages - membrane and soluble CD14 -can bind/neutralise LPS
- Conversely CD14 can also potentiate toxic effects of endotoxins, by transferring it to membrane CD14 or to cells that do not express it.
- CD14 does not structurally cross the cell membrane; has to associate w 2ary protein, toll-like receptor (TLR), that contains a transmembrane portion capable of comms w intracellular domain.
- TLR-4 is mandatory for responsiveness to endotoxin
- Once the CD14-TLR4-endotoxin complex is compiled at the cell surface, TLR-4 req help of a 160–amino acid molecule, MD2, to transmit a signal to the cytosol → intracellular signalling pathways incl NF𝞳B ⇒ stimulates inflamm response
- Most of the deleterious effects of endotoxin rx from overzealous endogenous synthesis of pro-inflammatory mediators and initiation of SIRS - AA metabolites most widely studied
Management of endotoxaemia
2 therapeutic options
- Polymixin B - a cationic antibiotic that has bacteriocidal properties & binds/neutralises endotoxin through direct interaction with lipid A (highly conserved so PB theoretically has broader endotoxin-binding capabilities than anticore-endotoxin antibodies)
- Can be stored at room temp. Does have inherent nephrotoxic and neurotoxic side effects when used IV at bactericidal doses, but for neutralisation, sub-bactericidal doses are efficacious without toxicity; recommended dose is 1000-6000IU/kg q 8-12hrs, care w azotaemic patients nonetheless. Effect is dose dependent, use higher end of dose range if ↑endotoxin anticipated
- 2) Anti-endotoxin antibodies - anticore antibodies have conflictin rx. Endoserum = hyperimmune serum from horses vacc w Salmonella typhimurium, Re mutant. Disadv of requiring refrigeration. Dilutied w sterile isotonic saline or LRS (1:10 to 1:20) and administered IV over 1-2 hr to reduce risk hypersensitivity reactions.
- Hyperimmune anticore plasma to Escherichia coli J5 (Equiplas) can be used in foals for concurrent tx of endotoxemia, septicemia, & FPT, given at 20-40 ml/kg, or in adults.
- Plasma products are expensive, req freezer storage, ∴ need thawed
- Others incl flunixin - 0.25 mg/kg IV q 8 hr is commonplace; benefit of this low-dose incl reduced risk of potential toxic side effects (not cited elsewhere)
Approximate % blood volume in adults and neonates
8% adults, upto 14% in fit horses
15% in neonates
