Deck 1 Flashcards
(437 cards)
1
Q
List the phases of healing
A
- Inflammation (w/in 5 days)
- Debridement (w/ inflam phase, neuts w/in 6 h, monocytes w/in 12 h)
- Repair/proliferation - w/in 3-5 d, last 2-4 weeks
- Maturation - 17-20 d after injury
2
Q
What are the mechanisms that hetastarch affects coagulation?
A
(1) Dilutional coagulopathy
(2) Factor VIII, vwf interactions (decreases up to 80% of FVIII and vwf w/ HES administration)
(3) Fibriongen polymerization (decreased interaction btwn FXIII and fibrin)
(4) Decreased availability of GIIbIIIa on surface of activated platelets
3
Q
What are eicosanoids?
A
Group of hormones produced from arachidonic acid that include prostaglandins, thromboxjnes, leukotrienes
4
Q
List the SOFA and qSOFA variables
A
SOFA (PF ratio, glasgow coma score, MAP, vasopressors, serum creatinine/UOP, bilirubin, platelet count)
qSOFA (RR > 22 bpm, altered mentation, SBP <= 100)
5
Q
What is PAI-1?…and the function?
A
Plasminogen activating inhibitor-1
Made from endothelial cells
Inhibits fibrinolysis
induced by inflammation
6
Q
What is TAFI and its function?
A
Thrombin activatable fibrinolysis inhibitor
Thrombin/thrombomodulin - helps activated protein C
- *thrombin activates TAFI**
- *protein C inhibits TAFI**
Fxn: inhibits fibrinolytic effect of plasmin
7
Q
What compounds inhibit fibrinolysis?
A
PAI-1 and TAFI
8
Q
Describe the effects of sepsis on coagulation…
A
(1) Procoagulant (induces TF, activates platelets, increased vwf)
(2) Reduced anticoagulation (reduces TFPI, depletes AT, reduces APC)
(3) Reduces fibrinolysis (Decreased plasmin, Increased PAI-1 and TAFI)
9
Q
What is ADAMTS-13
A
a disintegrin and metalloproteinase w/ a thrombospondin type 1 motif, member 13
Fxn: degrades large and ultra large monomers of vwf (decreases vwf activity)
Decreased in sepsis (which results in increased vwf and resultant pro coagulation)
10
Q
List causes and types of alterations in CVP waveforms
A
Tricuspid regurgitation = giant V waves
Simultaneous RA and RV contraction = cannon A waves
Cardiac tamponade = very rapid x decent
11
Q
Pimobendan MOA
A
PD III inhibitor
Sensitizes myocardium to Ca by altering binding of Ca to troponin C
= arteriolar and venous dilator
12
Q
Define Preload, Afterload, and Contractility
A
Preload = end diastolic volume, myocardial stretch
Afterload = systolic myocardial wall stretch, SVR
Contractility = intrinsic ability of myocardial fibers to shorten, peak systolic pressure to end systolic volume
13
Q
What is the wall stress formula
A
= p x r / t
t = wall thickness
Formula for after load stress (force at which ventricle has to contract against)
14
Q
List the mechanisms of intralipid therapy
A
(1) Lipid sink (sequesters lipophilic compounds into a newly created IV lipid compartment)
(2) provide myocytes w/ energy substrates - augments cardiac performance
(3) restores myocardial fxn by increasing iCa concentration
(4) increased fatty acid pool - overcomes inhibition of mitochondrial fatty acid metabolism
15
Q
how does hypermagnesemia affect ECG
A
Prolongs QRS complex
Shortens Q-T interval
Prolongs P-R interval
16
Q
Describe the MOA of glucose uptake in the brain
A
Insulin independnet
GLUT-1 = primary endothelial and astrocytes GLUT-3 = neuronal cell membranes
17
Q
What is the primary site of glucose metabolism?
A
Astrocytes
18
Q
At what level does the brain activates systemic changes to increase glucose?
A
when BG < 65
19
Q
How does the level of glucose differ in the brain and systemic system?
A
BG glucose 20-30% < than peripheral
20
Q
Describe the MOA of neuronal injury?
A
Decreased ATP –> dysfunction of NaK ATPase
results in increased iCa –> mitochrondria swelling and lipid per oxidation and DNA damage
results in glutamate-mediated excitotoxicity
21
Q
What is Horner’s syndrome?
A
Myosis
Ptosis
Elevated 3rd eyelid
Enophthalmos
= damage to the sympathetic fibers that leave spinal cord from C6-T2
22
Q
H2 receptor antagonists (MOA)
A
blocks histamine receptor on the gastric parietal cell
23
Q
What is the equation for Reynold’s number and what does it tell us?
A
> 2000 = turbulent flow
< 2000 = laminar flow
Re = v x d x p / n
v= velocity of blood flow d= vessel diameter p= density n= viscosity
24
Q
MOA of phenylpropanolamine
A
alpha-1 agonist (partial)
works on urethral sphincter
acts as a selective releasing agent of NE and epic - stimulates smooth muscles of trigone and proximal urethra - causing internal sphincter to contract
25
MOA of phenoxybenzamine
non-selective alpha agonist (urethral smooth muscle relaxant)
26
MOA of atracurium
neuromuscular blocker
antagonizes acetylcholine at the nicotinic receptors in the neuromuscular junction and induces paralysis of striated muscle
27
What is neonatal isoerythrolysis
develops in type A or AB kittens born to type B queens as anti-A antibody passed in milk
28
TRIM
Transfusion related immune modulation
Decreased NK and macrophage function
Shift from TH1 to Th2 phenotype
* *neutrophil activation**
* *endothelial cell activation**
leukoreduction not constantly shown to be beneficial
29
What HCT will maintain DO2 = VO2
in acute normovolemic hemodilution studies VO2 did not exceed DO2 until HCT <= 10%
30
What is in cryosupernatant
top portion of partially thawed FFP after a hand spin (5000g x 7 minutes)
Albumin
Globulin
Antithrombin
Protein C, S
2, 7, 9, 11, 10
31
Bernuli effect vs Venturi effect
Bernuli effect = increased velocity results in decreased pressure
Venturi effect = decreased pressure as fluid flows through constricted sectors
32
Maropitant MOA
NK-1 receptor antagonist
Blocks action of substance P in CNS and NK1-receptors in GI tract
**causes bone marrow hypoplasia in puppies < 11 weeks of age**
33
Misoprostol MOA
= prostaglandin E1 analog
w/ antacid and mucosal protective properties (stimulates mucus secretion and bicarbonate and increases gastric mucosal blood flow)
**anti-secretory effect on gastric acid = most important*
34
Sucralfate MOA
=octasulfate of sucrose w/ Aluminum hydroxide (binds to epithelial cells and acts as a protective barrier)
also stimulates local production of psotaglandins and binding to epidermal growth factor (favors mucosal repair)
35
Omeprazole MOA
irreversible inhibits H-K ATP on luminal side of parietal cells (stops secretion of H+ ions into gastric lumen)
* *inhibits P450 enzymes**
* *decreased anti platelet activity by clopidogrel**
* *clearance of valium**
* *decreased Mg**
36
Aminophylline MOA
phosphodiesterase inhibitor
bronchodilator
mild chronotropic efecst
**temporary increase in HR w/ sick sinus syndrome**
37
Erythromycin MOA
motilin receptor agonist
38
Cholinomimetic drugs
= bethanechol, ranitidine, and knizatide
bethanechol = true cholinomimetic drug that binds to muscarinic receptors
ranitidine and nizatide = inhibit acetylcholinesterase
39
Cisapride MOA
5-HT4 agonist
enhances gastric emptying while increasing gastroesophageal sphincter pressure
40
Promazine derivatives
= chlorpromazine and acepromazine
MOA: antidopaminergic and antihistaminic (block CRTZ at higher dosages)
at higher dosages --> vasodilation --> sedation
41
Metoclopramide MOA
(1) antidopamineric activity
(2) blocks 5-HT3 receptors (potent blocker of CRTZ)
(3) 5HT4 agonist
dose reduce in renal disease
keep IV solution covered
42
Ondansetron MOA
5HT3 receptor antagonist
**peripherally and centrally (CRTZ and medullary vomiting center (MVC))
43
Proton pump inhibitor (MOA)
irreversibly inhibits hydrogen-potassium adenosine triphosphate on luminal side of parietal cell --> stopping secretion of H+ ions into gastric lumen
44
Gabapentin MOA
bindin to the alpha2-8 subunit of neuronal voltage-gated Ca channels
--> inhibition of excitatory neurotransmitters
45
Zonisamide MOA
sulfonamide drug
- -> inhibits Na-gated channels
- -> inhibits T-type Ca channels
- -> modulation of dopaminergic activity
- -> enhancement of GABA activity in CNS
- -> inhibition of carbonic anhydrase activity
46
Keppra MOA
binding to synaptic vesicle protein (SV2A) --> decreased release of neurotransmitter into synapse
47
KBr MOA
hyperpolarization of neuron via movement of bromide ions intracellularly through Cl channels
48
Phenobarbital MOA
=barbiturate that facilitates GABA-ergic activity by prolonging opening of Cl channels associated with GABA(A) receptor
**also inhibits glutamate votalge-gated Ca Chanels**
49
Vasodilatory shock definition
final common pathway for long-lasting and severe shock of ANY cause
occurs as a result of vascular smooth muscle failing to constrict
MOA (1) K ATP channel activation
(2) NO production
(3) vasopressin depletion
50
Classification of hemorrhagic shock
I < 15%. **normal blood pressure**
II 15-30%
III 30-40%
IV > 40%
51
Digoxin MOA and toxicity
MOA = increase cardiac contractions by increasing Ca ions in muscle fibers -- via inhibition of NaKATPase in cardiac cell membranes --> decreasing Na across membrane and slows activity
Digoxin toxicity --> decreasing K; competitively binds on Na/K pump (increases cardiac contractility --> tachyarrhymias)
Tx: Digibind (antibodies against digoxin)
**also for oleander toxicity
52
Dexmedetomidine MOA
alpha2 agonist --> inhibition of adenyl cyclase, activates K channels, accelerates Na/H exchange, inhibits Ca channels
inhibits SNS
inhibits insulin release
inhibits ADH release
53
Chlorpromazine
Centrally acting
- antidopineregic/antihistaminic effects that block CRTZ
- anticholinergic, antispasmodic, alpha-blocking effects
54
Metoclopramide MOA
```
5HT4 agaonist
dopaminergic antagonist
5HT3 antagonist (CRTZ)
```
**drug is sensitive to light**
55
Etomidate
- nonbarbiturate hypnotic acts at level of reticular-activating system
- imidazole compound that depresses CNS fxn via GABA
56
MOA of phenothiazine sedation
= acepromazine
acts as alpha2 antagonist --> peripheral vasodilation (+/- decreases BP)
57
Propofol MOA
peripheral vasodilator
| myocardial depressant
58
Butorphanol MOA
K agonist
| mu antagonist
59
Ex of vasodilators vs vasoconstrictors
Vasodilators
(1) NO
(2) Prostacyclin
Vasoconstrictors
(1) Thromboxane
(2) Angiotensin II
(3) NE/epi
(4) Vasopressin
(5) Endothelian-1
60
ACE inhibitors
inhibit conversion of angiotensin I to II
Results in decreased angiotensin I and II and decreased bradykinin
Effects
(1) decreased Na retention (reduced plasma volume)
(2) decreased aldosterone (decreased Na/H20 retention)
(3) decreased growth factors (decreased glomerular hypertrophy)
(4) decreased proteinuria (maintains heparin sulfate layer)
61
What is the CNS ischemic response?
Occurs in the vasomotor center of medulla
- Increased CO2
- Increased H+ ions
- activates at BP of < 50 mmHg
- -----> powerful sympathetic stimulation
Results in (1) massive vasoconstriction (2) increased HR and contractility
62
Vasopressin - where produced, stored, and released
Produced: supraoptic and paraventricular nuclei of hypothalamus
Stored: posterior pituitary gland
Released: in response to hypovolemia
63
Phosphodiesterase
Enzymes responsible for degradation of cGMP and cAMP
w/ inhibition (ie pimobendan (III), sildenafil (V))
**get increased concentration of cAMP and cGMP and this results in increased concentration --> relaxation**
64
Oxygen extraction ratio equation
= (CaO2 - CvO2) / CaO2 = VO2 / DO2
normal = 0.2 to 0.3
65
N-acetylcysteine (MOA)
bkdown of disulfide bonds in thick airway mucous (tx pneumonia)
precursor of glutathione (free radical scavenger)
66
Neurotransmitters
| excitatory vs inhibitory
Excitatory : glutamate, acetylcholine, ammonia
(depolarizes neurons by allowing Na into the cell)
Inhibitory: GABA , Benzos, glycine
(hyper polarizes by allowing Cl into cells)
67
Bethanechol MOA
parasympathiomimetic choline carbamate (muscarinic receptors)
selectively stimulates muscarinic receptors w/o any effects on nicotinic receptors
68
Tamsulosin MOA
alpha-1A selective antagonist (urethral smooth muscle relaxant)
1B = found in blood vessels
69
What is the MOA of antithrombin
Inhibits IIa and Xa
fxn potentiated by heparin or GAG on endothelial surface or WBC
70
What is contraction alkalosis?
= volume loss (ECF) that promotes metabolic alkalosis
**misleading term - the underlying mechanism is chloride depletion (alkalosis is not corrected by volume replacement w/o Cl replacement but is corrected by Cl replacement w/o fluid replacement)
71
What are the types of Vw disease?
**high MW multimers are the most effective**
Type I = partial quantitative deficiency, most common
(Dobies, Rotts, GSD)
Type II = decreased vwf and disproportionate loss of high MW multimers (GSHP and GWHP)
Type III = severe quantitative deficiency (sheltie, chespake, Scottish terrier)
72
What is the caudal vena cava distensibility index?
= (CVCmax - CVCmin) / (CVCmax)
Normal = 0.2 to 0.5
Volume depletion > 0.5 to 0.6 (fluid tolerant)
Elevated CVP: static CVC distension (< 0.2 = fluid intolerant)
73
Equation to estimate PA pressure using TV max
TRVmax = tricuspid regurgitate max velocity
```
= (TR Vmax)^2 x 4 + estimated RA pressure
Normal 20-30 mmHg
Mild PH > 35 to 50
Moderate PH > 50-80
Severe > 80
```
Estimated RA pressure
= 5 if no heart failure
= 10 if impending RHF
= 15 if in RHF
74
Definition of cardiac tamponade and how does pulses paradoxus definition apply
= intra-pericardial pressure that exceeds RVED pressure causing diminished diastolic filling and low CO
= RA diastolic collapse
pulses paradoxus = > 10 mmHg change in pressure
75
What is a normal LA:Ao ratio?
> 2:1 suggests CHF
measure aortic diameter at end diastole
LA at maximal systole
76
How do you calculate fractional shortening?
= ( LVIDd - LVIDs ) / LVIDd
Normal 28 to 45% (dogs) and 30-50% (cats)
77
What is the RV:LV ratio and how does this give you data clinically?
> 0.6 suggests RV enlargement
w/ abdominal effusion suggests R-CHF
w/ respiratory distress suggests pulmonary
78
Stroke volume
SV = EDV - ESV
**volume of blood ejected from heart w/ each beat**
79
RIFLE criteria
```
Risk
Injury
Failure
Loss
End-stage
```
80
Osmolality equation
= 2xNa + (BUN/2.8) + (glucose/18)
81
Dopaminergic receptor (D2) antagonists
results in increase Ach release from postganglionic cholinergic neurons and promote intestinal smooth muscle contract and peristalsis
ex. doperidone (D2 receptor antagonist)
ex. metoclopramide (D2 receptor antagonist)
82
Serotonin receptor (5-HT) agonists/antagonists
5HT is released from enterochromaffin cells of GI mucosa
5HT4: regulates motility of the gut (presynaptic 5-HT4 stimulates Ach release from postganglionic cholinergic neurons --> smooth muscle contraction
5HT3: antagonism used to treat nausea
83
Domperidone MOA
D2 antagonism
a2 and B2 antagonism
84
Cisparide MOA
5HT4 agonism
5HT3 antagonism
5HT1 antagonism
85
Atot
sum of nonvolatile weak acids
= albumin + phosphorus
86
SIG
= (Na+Ca+Mg+K) - (HCO3+Cl+albumin+phos)
or SID - (HCO3+Atot)
87
What is a normal SID
= Na+K - Cl
=Na+K+Mg+Ca - Cl+anions
40 to 45 mEq/L
88
How do crystalloids affect plasma pH as defined by stewart
SID > HCO3 --> increase pH (alkalosis)
SID < HCO3 --> decrease pH (acidosis)
SID = HCO3 --> no change pH
**dependent on SID and HCO3**
89
Factor Xa inhibitors
Rivaroxaban
90
Warfarin MOA
Inhibits vitamin K epoxide reductase and Vitamin K recycling
91
Unfractionaed heparin
enhancement of antithrombin activity on FXa and thrombin
92
At what point does effectiveness of heparin decrease with loss of antithrombin?
< 60% of activity
at < 30% of activity --> critical risk for thrombosis
93
Clopidogrel MOA
Inhibits P2Y12
P2Y12 antagonist
--> prevents platelet activation and aggregation stimulated by ADP
delay of 2-5 days to maximal effect
94
Thromboxane A2
= potent platelet agonist stimulating further platelet activation and promoting platelet aggregation
95
Aspirin MOA
irreversible inhibits cyclooxyrgenase --> reducing synthesis of prostaglandins (prostacyclin - produced from endothelium) and (thromboxane A2 - produced from platelets)
96
LMWH MOA
enhancement of antithrombin activity on FXa and thrombin
**more reliable than UnFH (increased anti-Xa activity) and decreased binding to thrombin**
97
TPA MOA
= tissue plasminogen activator
used for thrombolysis
converts plasminogen to plasmin
=acts at site of thrombus because has a high affinity for fibrin-bound plasminogen compared to freely circulating plasminogen (safety advantage over previous thrombolytic agents)
ex. streptokinase and urokinase
98
MOA of refeeding syndrome
increased glucose --> insulin release
| = intracellular movement of PO4, Mg, K
99
Metoclopramide MOA
D2 antagonist
5HT4 agonist
5HT3 antagonist
100
How do opioids inhibit GI motility?
inhibit release of Ach = increase colonic muscle tone and decrease propulsive activity in GI tract
101
Erythromycin MOA
```
motion agonist (increases GI motility)
5HT3 antagonist
```
102
What is motilin
peptide synthesized by endocrine cells of small intestinal mucosa
- regulates interdigestive MMC (migrating motor complex)
- -> strong contraction, promotes GI motility
103
What is ghrelin
= peptide produces by parietal cells of gastric mucosa as an endogenous ligand for growth hormone
increases gastric emptying and MMC (phase-3 like activity)
104
Ranitidine MOA
H2 receptor antagonist
acetylcholinesterase inhibitor
105
Nizatidine MOA
H2 receptor antagonist
acetylcholinesterase inhibitor
106
Hyperlactatemia types
I = increased lactate w no change in pH
```
II = increased lactate w change in pH
2A = due to inadequate O2 delivery
2B = occurs despite adequate O2 delivery
```
107
Examples of 2A and 2B hyperlactatemia
2A
- shock
- hypo perfusion
- severe hypoxemia PO2 < 40
- severe anemia < 15%
- CO toxicity
- muscle activity
2B
B1 (disease) DM, neoplasia, sepsis, pheochromocytoma
B2 (drugs) EG, xylitol, acetaminophen, terbutaline, Epi
B3 (due to inborn errors in metabolism) glycogen storage disease, pyruvate dehydrogenase, etc
108
Baclofen
GABAb receptor agonist
prevents Na channels from opening and interfere w the action potential
109
Effective vs ineffective osmoses
Effective
- Na
- Cl
- Mannitol
- Ketoacids
- Lactic acid
- Phosphates
- Sulfates
- contrast solution
Ineffective
- BUN
- Methanol
- EG
- Ethanol
110
How does AVP regulate water homeostasis?
(1) by regulating fast shuttling of aquaporin-2 to the cell surface
(2) stimulating the synthesis of messenger ribonucleic-acid-endocing aqua-porin-2
111
How does sepsis alter vasomotor tone?
(1) induce expression of pro inflammatory cytokines that inhibit expression of genes for receptors for alpha1 agonists, antiogensin II, vasopressin --> decreased vasomotor responsivenesses
(2) proinflamm cytokines mediated by NF-kB
112
V2 receptors
found primarily on the basolateral membrane of the distal tubule and in principal cells of cortical and medullary renal collecting duct
113
MOA
(1) Pimobendan
(2) Spironolactone
(3) Sildenafil
(1) Phosphodiesterase III inhibitor
- positive isotropy
- vasodilatory effects
(2) Aldosterone antagonist
(3) Phosphodiesterase V inhibitor --> causes NO-mediated vasodilation secondary to cGMP
114
SVR index equation
= {(MAP-CVP) * 80} / CI
115
Pulse pressure variation equation
= 100 x (PPmax-PPmin) / {PPmax+PPmin}/2
116
Inducers and Inhibitors of P450 enzymes
```
Inducers
Barbituates
Omeprazole
Rifampin
Glucocorticoids
St John's wort
```
```
Inhibitors
Cimetidine
Chloramphenicol
Ketoconazole
Macrolides
TMS
Metoclopramide
Cyclosporine
```
117
Hypersensitivities - Types
Type1 - IgE mediated
Type2 - IgG mediated (ex IMHA, IMPA, ITP)
Type3 - immune complex reaction (IgG-IgM mediated) (ex serum sickness, SLE, glomerulonephritis)
Type4 - delayed type (antibody independent) (ie graft rejection and contact dermatitis)
118
How do you calculate the albumin deficit?
(deficit is in grams)
= 10 x (desired albumin - patent albumin) x BW (kg) x 0.3
119
Free water deficit equation
= {(current Na) / (normal Na) - 1 }. x 0.6 x BW (kg)
120
% dead space equation
= (PaCO2 - EtCO2) / PaCO2 * 100
121
Stages of wound healing
(1) Inflammation
(2) Debridement
(3) Repair
(4) Maturation
122
Vasopressin MOA
released from nearhypophysis in response to decrease in BP
- -> potentiates effects of NE
- -> inactivates KATP channels in vascular smooth muscle
- -> decreased synthesis of iNos
------> Vasoconstriction
123
Clovidipine MOA
Ca channel blocker
* *used over hydralazine (can titrate)
* *transition to amlodipine
124
Poiseuille's law
R = 8 * n * l / (pi x r^4)
125
Preload definition
= end diastolic wall stress / volume
= end diastolic pressure better represents wall stress
**stress of muscle prior to contraction**
126
Ejection fraction equation
= effectiveness of ventricles in ejecting blood (fraction of EDV ejected in one SV)
normal = 55%, is an indicator of contractility
Ejection Fraction = SV / EDV
127
Firing nodes of various pacemakers in the heart
SA node = 70-80 bpm
AV node = 40-60 bpm
Bundle of Hiss = 40 bpm
Purkinje fibers = 15-20 bpm
128
What are the effects of hypocalcemia on AP and ECG
AP - prolongs phase 2
ECG - prolongs ST segment and QT interval
129
Laplace's law
wall stress = { pressure x radius } / 2*wall thickness
as preload increases --> wall stress increases
130
Glucagon MOA
glucagon binds to receptor sites distinct from L-type Ca channels and adrenergic receptors
stimulates adenyl cyclase --> cAMP formation --> Ca influx and Ca release from SR
stimulation of SA and AV nodes
inotropic, chronotrpic, dromotropic effects
131
Specific types of B-blockers and if B1 or B2
Propanol and sotalol = B1 and B2
Atenolol and Esmolol = B1
132
Carbonic anhydrase inhibitors MOA
acetazolamide inhibits type II (cytoplasmic) and type IV (membrane) carbonic anhydrase from the proximal tubular epithelium -->
decrease in proximal reabsorption of NaHCO3
- -> metabolic acidosis
- -> natriuresis
133
Loop diuretics MOA
binds to and inhibits the Na-K-2Cl cotransporter on apical membrane of epithelial cells of thick ascending limb of loop of henle
increases renal blood flow
inhibits Cl flux in macular densa --> inhibits tubuloglomerular feedback
134
thiazide diuretics MOA
inhibits NaCl cotransorter on apical membrane of distal tubule
used for anticalciuretic properties and diuresis
135
What is the function of calcitriol?
it is a metabolite of Vitamin D3
Necessary for normal absorption of Ca by the GI tract and for its deposition in bone
In patient's w/ renal disease, the kidneys' ability to produce calcitriol is impaired and levels of this hormone are reduced
136
Why no baytril with SSTIs?
b/c baytril has limited activity against streptococcal infections and may cause bacteriophage-induced lysis of S. Canis --> enhancing pathogenicity
137
What is the mechanism of mitochondrial dysfunction (MODS)
Neutrophils release superoxide and NO produced from vascular endothelium combine to form peroxnitrite --> causes inhibition of mitochondrial respiration and synthesis of ATP (=cytopathic hypoxia)
138
Fenoldopam MOA
pure dopamine type-1 receptor agonist
| causes renal vasodilation w/o alpha and B-activation seen w/ dopamine
139
Name the types of necrotizing soft tissue infections
(1) polymicrobial (mixed anaerobes/aerobes)
(2) mono microbial (beta-hemolytic streptococcus)
(3) G - monomicrobials (clostridia, marine organisms)
(4) fungal (candida)
140
What results in anti-coagulation and fibrinolytic inhibition in sepsis
Downregulation of antithrombin, TFPI, TPA, Protein c/s
Upregulation of PAI-1
141
Definition of venous O2 saturation
= a measure of the saturation of Hgb w/ O2 in venous blood
--> reflective of a difference between DO2 and VO2
142
Why is it not appropriate to prescribe ampicillin to an enterococcus susceptible to ampicillin?
enterococcus do not normally produced B-lactamses but when exposed to B-lactamase-inhibitor drugs --> induction of the enterococci producing B-lactamase occurs
**penicillins along only arrest bacterial growth and aminoglycocides won't kill alone but combo will kill the organism**
143
What is the mechanism of methicillin resistance?
mecA gene that endorse production by a modified penicillin binding protein (PBP)
B-lactam unable to bind, so cell wall synthesis is NOT inhibited
144
What's in the qSOFA
RR > 20 bpm
SBP < 100 mmHG
altered mentation
145
What effect does NE or vasopressin have on cytokine levels?
Decreases them --> vasopressin will decrease cytokines more than NE in 1st 24 hours of therapy and decreased ein cytokine level has been linked to survival
146
What causes clearance of NETS (in the lungs)?
Surfactant A and D (but this is deficient in ALI/ARDS so NETs clearance is reduced)
147
Mechanism of hepatic dysfunction (MODS)
Primary Stage = hypo perfusion
- decreased lactate clearance, decreased protein synthesis, decreased gluconeogenesis, decreased glycogenolysis
Secondary stage = Kupher cells activated --> get increased pro inflammatory cytokines, increased nitric oxide, and increased ROS
148
Septic shock - what is CO and SVR?
High cardiac output
| Decreased SVR --> producing hypotension despite adequate fluid resuscitation
149
NAC (MOA)
Regenerates glutathione stores
ROS scavenger
Enhanced NO availability --> vasodilation
150
Why aren't alpha-adrenergic agonists used alone?
alpha-adrenergic drugs --> increased after load and may decrease cardiac output if used alone (therefore decrease regional blood flow)
**so use drugs w/ some beta or dopamine receptor activity to off set them**
151
VEGF
is a hypoxia-driven responsive angiogenic factor that is also associated with increased vascular permeability
**dysfunctional endothelium = motor of MODS**
152
Platelets role in inflammation in sepsis
Platelets exacerbate expression of procoagulant products (TF, fVa, fVIIIa) recruit additional platelets, express fibrinogen receptor, part of structure of clots
153
Role of C-type natriuretic peptide (cNP) in sepsis
expressed by vascular endothelium and macrophages in response to inflammatory stimuli (TNF-alpha, IL-1beta, TGF-beta)
exhibits antimicrobial activity by inhibiting microbial growth and modifying pathogenicity of microorganisms
NT-cNP has longer half life than CNP
154
Mechanism of decreased vascular tone w/ sepsis
Increased iNOS
decreased vasopressin (deficiency of vasopressin)
155
SVR index
={ ( MAP - CVP ) * 80 } / CI
156
Parvovirus affects which stage of the cell cycle
late S phase or early G2 phase
157
At what ventricular end diastolic pressure do you see cariogenic pulmonary edema?
> 20 to 25 mmHg
158
What is a bacteriophage?
= viruses that infects and replicates w/in bacteria and ultimately cause bacterial death
(1) lytic phage --> cause bacterial cell lysis
(2) temperate phage --> allows bacterial cell to survive and reproduce w/ the phage's progeny being reproduced in bacteria
159
What is CARS and what 4 cytokines are associated?
compensatory anti-inflammatory response syndrome
IL4
IL10
IL13
TGF-beta
160
# Define they types of bacterial resistance
- intrinsic
- circulstantial
- acquired
Intrinsic = inherent features of a microorganism that results in lack of activity of an antimicrobial drug (ie pseudomonas)
Circumstantial = in vitro test predicts susceptibility in vivo - lacks efficacy (drug may lack ability to penetrate into site) or cannot work b/c of low pH (inactivation in acidic urine)
Acquired = change in phenotypic characteristic (ie exposure to previous antibiotics --> MDR)
161
Antimicrobial resistance grading
- MDR
- XDR
- PDR
MDR = no susceptible to at least one agent in 3 or more classes of antimicrobials
XDR = susceptible to only 1 or 2 classes
PDR = not susceptible to all known or licensed antimicrobials
162
Examples of mechanism of MDR
mecA gene (MRSA)
amino glycoside modifying enzymes (AME)
alterations in penicillin-binding protein (PBPS)
163
Why re Rottweilers and doberman pinschers more susceptible to parvovirus
increase monocyte TNF-alpha production compared w/ other breeds
164
MOA that vasopressin causes vasoconstriction
activating V1 receptors
--> this increases intracellular Ca via phosphatidylinositol biphosphonate cascade
165
MOA of sepsis-induced AKI
renal tubular dysfunction w/ activation of the tubuloglomerular feedback mechanism
166
Mechanism of MODS
1. cell/tissue hypoxia
2. induction of cellular apoptosis
3. translocation of microbes from GI tract
4. immune system dysregulation
5. mitichondrial dysfunction
167
Examples of early and late cytokines
Early - TNF-alpha, IL-1beta
Late - IL-6, and HMGB-1
168
What inhibits Nf-KB?
Lipoxin A
169
What are resolvins?
attenuate TNF-mediated NF-kappa B activation
Decreased neutrophil migration
modifies genes to promote resolution
170
What is 15d PGJ2
anti-inflammatory produced by COX-2 down regulates adhesion molecules, inhibits macrophage activation, suppresses NF-kB
171
What is efferocytosis
neutrophil expression "fine me, eat me" signals to attract macrophages
Find me: LPC, S1P, Cx3CL2, ATP, UTP
Eat me: phosphatidylserine
172
What is the role of CRP
= acute phase protein
ROLE: promotes binding of complement/opsonization
induction of cytokines
inhibition of chemotaxis
modulation of neutrophil fxn
173
What mechanism of endothelial cells make them anti-coagulant
Thrombomodulin --> activates protein C, TFPI, Heparin, TPA
In sepsis, endothelial cell dysfunction dampens this pathway and increase procoagulant activity
174
Mechanism of dysregulation of inflammation and coagulation w/ sepsis
Bacterial infection and host inflammatory cytokines up regulate TF levels --> TF + fVIIa --> coagulation cascade
hemostatic balace in septic patients favors procoagulant and antifibrinolytic sate initially --> progression over time to a hpocoagulable state depends on host protein synthesis
natural anticoagulant and fibrinolytic processes initiated (but down regulated by sepsis)
Antithrombin TF pathway inhibited
Protein C/S pathway inhibited
Reduction of normal aPC anticoagulation and anti-inflammatory effects
175
Pro vs anti-inflammatory cytokines
Pro: TNF-alpha, IL6, IL1beta, IL8, Ifn gamma
Anti: TGF-beta, IL10, IL4, IL13
176
What is TFPI
Tissue factor plasminogen inhibitor
177
Mechanism that angiotensin II, NE, endothelian result in vasoconstriction...
increase smooth muscle calcium
178
What are the secondary messengers of alpha1, alpha2, and beta1/beta2 ?
Alpha1 = phospholipase C
- > PIP2 --> IP3 + DAG
- -> protein kinase C, increased Ca from SR
Alpha2 = Gi --> inhibit adenylate cyclase, may stimulate phospholipase C
B1 and B2 = Gs --> AC --> cAMP
--> increase protein kinase and increase Ca from Ca channel and SR
179
How does pimobendan sensitize myocardium to calcium
altering binding of Ca to troponin C
180
Fxns of pimobendan
phosphodiesterase III inhibitor
arteriolar and venous dilator
181
What is enhanced automaticity
net gain of + ions intracellular causing steepening of phase 4
182
What is abnormal automaticity
when pacemaker shifts away from SA node
slow atrial, Jxn, ventricular escape rhythm
occurs when maximal diastolic potential is reduced
183
Stimulators and inhibitors of AVP release
Simulators: Ach, angiotensin II, histamine, dopamine, catecholamines
Inhibitors: GABA, opioids, ANP
184
List the AVP receptors and fxn
V1: smooth muscle, liver, renal medulla, brain, testes
V2: renal collecting duct and increase water
V3: anterior pituitary--> ACTH secretion
oxytocin receptor - myometral, mammary contraction
185
Mechanisms of loss of vasomotor tone
activation of ATP sensitive K channels
Increased synthesis of NO
AVP deficiency
186
Equation for SVR
= (MAP - CVP) / Q * 80
187
Equation for PVR
= (PAP - PAOP) / Q * 80
188
What is the Fick principal?
uptake of any substances is equal to the product of blood flow to the organ and arteriovenous concentration difference
Q = VO2 / (CaO2- CvO2)
189
What is the shunt equation?
Qs/Qt = (CcapO2 - CaO2) / (CcapO2 - CvO2)
CcapO2 = (Hgb)*(Scapulas)*1.34 + (PAO2 x 0.003)
190
Equation for oxygen extraction ratio
OER = VO2 / DO2
OER = CaO2-CvO2 / CaO2
191
Equation for CaO2
= (SaO2 * 1.34 * Hgb) + 0.003* PaO2
192
Equation for DO2
= CO * CaO2
CaO2 = (SaO2 * 1.34* Hgb) + (0.003 * PaO2)
193
Equation for VO2
= CO * (CaO2 - CvO2)
194
List 4 determinants of CVP
(1) blood volume
(2) venomotor tone
(3) intrathoracic pressure
(4) RA fxn
195
List the 3 GLUT proteins and location
GLUT-1 = in brain and placenta,
GLUT-2 = liver, kidney, SI, pancreas, B cells
GLUT-4 = muscle, adipose, cardiac tissue, in insulin mediated uptake
196
MOA of insulin resistance
Decrease in GLUT-4 activity by glucagon and cortisol
Impairment of insulin stimulated GLUT-4 movement to plasma membrane
Decreased glycogen synthase and pyruvate DH which metabolizes glucose to glycogen and pyruvate
--> increase in intracellular concentration
197
MOA of fenolodpam and RBF
Specific DA-1 agonist
more specific and potent than dopamine
causing renal vasodilation
maintains RBF despite systemic hypotensin
not shown clinically to benefit and possible worsening of renal injury
198
List aPC's antiinflammatory properties
inhibits TNF release
NFKb activatino
leukocyte adhesion
TF expression
increased fibrinolysis via inhibition of plasminogen activator inhibitor (PAI-1)
199
Protein C - where synthesized, what activates it, and fxn
Synthesized by the liver
Activated by thrombomodulin
Inactivates V and VIII
200
Antithrombin fxn
Binds to Xa
if bound to heparin binding domain enzymatic activity >1000x
if heparin molecule long enough, will bind AT and thrombin...if not inactivates Xa just as well
201
Definition of a massive transfusion?
> whole blood volume in a 24 h period
> 1/2 blood volume in a 3 hour period
1.5 ml/kg/min over 20 minutes (30 ml/kg over 20 minus) or 1/3 blood volume in a dog over 20 minutes
202
Abnormalities associated w massive transfusion
```
Hypocalcemia
Fluid overload
TRALI
Hypomagnesemia
Increased potassium
Decreased pH
Secondary coagulopathy
Hypothermia
Metabolic acidosis
Immunosuppression
```
203
What causes the electrolyte changes w/ a massive transfusion
Hypocalcemia and Hypomagnesemia
- b/c citrate is added to the blood products as an anticoagulant. Citrate binds to Ca and Mg.
Hyperkalemia in stored blood b/c inactivation of NaKATPase pump by cold storage temps
204
Hemostatic effects of massive transfusion
Decreased platelets
Hypofibrinogenemia
Dilutional coagulopathy
205
Components of acute traumatic coagulopathy
Hyperfibrinolysis
Altered coagulation enzyme activity
Release of activated protein C
206
Whatis the bloody viscous cycle
Hypothermia
Acidosis
Inability to establish hemostasis
207
List nonimmunologic transfusion reactions
Bacterial growth
Disease transmission (ehrlich, etc)
Ammonia levels in stored blood rise significantly w/ time so patients who receive lg volumes of blood --> risk for hyperammonemia
208
What is the diving reflex
Mediated by the trigeminal nerve
Results in bradycardia, hypertension, preferential shunting of blood to the cerebral and coronary circulations
209
Fxn of the macula densa
detectors of the flow rate and composition of the fluidw/in the nephron at the very end o the thick ascending limb
**detector cells contribute to the control of GFR and control of renin secretion **
210
What is total lung capacity
= volume of gas in the lungs at the end of maximal inspiration
**expiratory muscles are also contracting strongly at en dog maximal inspiration**
211
What is residual volume?
Volume remaining after maximal expiration
212
Common types of type B hyperlactatosis
B1 (diseases): liver disease, DM, sepsis, renal failure, neoplasia
B2 (drugs/toxins): ethylene glycol, propylene glycol, epi
B3: mitochondrial
213
What is the Cori cycle?
production of lactate in tissue and conversion to glucose by another
Lactate + 2H+. Glucose
214
What is CRP
acute phase protein
stimulated via IL-1 that binds phosphorylation on membrane and helps initiate complement
215
List the 3 different types of vwf
(1) decreased quantity but normal quality
(2) normal quantity but lower # high molecular weight multimer
(3) virtually absent
216
Impaired fibrinolysi
occurs w/ inflammation
Plasminogen AI-1 is upregulated
Decreased tissue plasminogen activator
= fibrin deposition and microthrombi
217
List the 4 mechanisms of heat loss
(1) Convection - loss to surrounding air
(2) Conduction - loss to objects that ar eincontact
(3) Radiation - loss to surrounding sturcutes that don't contact (ie wall)
(4) Evaporation - loss of heat from moisture of body surface or respiratory tract
218
Histamine synthesized by? and what are the 4 receptors
Synthesized by mast cells, basophils, platelets
H1: vasodilation, increased vascular permeability, stimulates endothelial cells to convert L-arginine to NO
H2: stimulates gastric acid secretion, vasodilation, increased HR and ventricular contractility
H3: inhibit NE release
H4: chemotaxis and mast cell cytokine release
219
Acetaminophen MOA
Acetampinophne is metabolized by cytochrome P450 to N-acetyl-p-benzoquinoemine (NAPQI)
NAPQI is detoxified by glutathione and nontoxic substances w/ excess dosing and exhaustion of glutathione --> Increase NAPQI --> hepatocyte damage and fulminant hepatic failure
220
MOA of physostigmine
acetylcholinesterase inhibitor
used for anticholinergic toxicity
221
Digoxin toxicity
cardiac glycoside toxicity
- inhibition of Na-K-ATPase on cellular membrane
- -> high grade AV block
222
Describe phospholipids on cell membrane
In resting cells outer membrane is phosphatidyl choline, sphingomyelin, and sphingolipids
Phosphatidyl serine (PS) and PE are only on inner surface
When cells activated/injured -> flipase brings PS out
Flopase brings PC in
Scrambalase brings PS and PE out and PC IN
223
What is the only factor that circulates in active form?
VII
224
TAFI
increases resistance to plasmin induced fibrinolysis
- -> induced by thrombin/thrombomodulin
- -> inhibited by APC
225
PAI-1
reduces production of plasmin
inhibited by APC
226
Protein Z
inactivates factor Xa
227
What is Boyle's law?
P1 V1 = P2 V2
228
What is the burns rule of 9?
```
Forelimb = 9%
Hindlimb = 18%
Dorsal Thorax = 9%
Ventral Thorax = 9%
Dorsal abdomen = 9%
Ventral abdomen = 9%
Head/neck = 9%
```
229
Calculate the fluid requirement for burns
1-4 ml/kg x %TBSA
over 24 hours
230
Calculate the plasma requirements for burns
0.5 ml/kg x % TBSA after 12-24 hours
**colloids usually not start until 12 hours up to 24 hours when vascular permeability is stabilized**
231
Aminocaproic acid MOA
binds to fibrin competitively and inhibits the binding of plasminogen
232
Most frequent bacteria w/ SSTI and NSTI
Beta hemolytic strep although polymicrobital infection is common
233
Pathophysiology of neurogenic edema
massive sympathetic outflow causing pronounced vasoconstriction and systemic hypertension
- -> marked LV after load -> decrease stroke volume --> blood accumulation in the pulmonary circulation
- -> increase transient pulmonary hydrostatic pressure
234
What is the free water deficit equation?
= (Na current / Na normal) - 1) * 0.6 * BW
This gives you the volume in liters, convert to ml and divide over estimated hours to decrease Na by NO MORE than 0.5 to 1 meq/l/hour
235
What is the Na deficit calculation
(Target NA - patient NA ) * 0.6 * BW
236
What is the equation for alveolar ventilation
Va = RR x (Vt - Vd)
237
What is the equation for minute ventilation
= RR x TV
238
Equation to calculate MAP
= DAP + (SAP-DAP)/3
239
List positive and negative acute phase proteins
Positive
- CRP
- Fibrinogen
- Prothrombin
Negative
- Albumin
- Protein C
- Protein S
- Antithrombin
240
How does hetastarch decrease platelet function
binds directly to GPIIb/IIIa receptor on the platelet surface and inhibits binding of fibrinogen to the receptor
--> thus preventing outside to inside signaling, platelet up-regulation and ultimately formation of a platelet plug
241
What is the shock index?
= HR / SBP
**normal in people 0.5 to 0.7
cutoff in vet med > 0.9
242
What is antithrombin?
inhibits thrombin and factor Xa
lesser effect on IX and fVIIa-TF complex
243
What is protein C
inhibits factors Va and VIIIa
244
What is TFPI
Inhibits fVIIa-TF complex and factor Xa
245
What does G measure
= clot shear elastic
MA is used to derive
G = 5000 x MA (100-MA)
**measure of overall coagulant status**
246
Describe the 3-phase model of CPA
(1) electrical phase
- minimal ischemia
- lasts 4 minutes
(2) circulatory phase
- associated w/ energy depletion
- potentially reversible cellular damage
- btwn 4 and 10 minutes after CPA
(3) metabolic phase
- ischemic injury
- may require more advanced strategies than conventional BLS and ALS to reinstate cellular fxn
247
How do you determine the ATT score
Based on 6 parameters
- perfusion
- cardiac
- respiratory
- muscle/integument/eye
- skeletal
- neurologic
Score 0-3 and add up
score of 0 = slight/no injury
score of 3 = severe injury
total <= 18
Each point increase ATT score --> 2.3 to 2.6x decreased likelihood of survival
248
Compare contrast CO2 as measured by
PaCO2
PvCO2
EtCO2
```
PvCO2 = 3-5 lower than PaCO2
PaCO2 = middle
EtCO2 = 3-5 lower than PaCO2
```
249
Causes of metabolic acidosis (general)
w/ hypercholermia = b/c of HCO3 loss
w/o hyperchloremia = b/c gain of acid
250
What is measured/calculated on a blood gas machine?
What equation is used to calculate
How do you calculate?
```
pH = measured
pCO2 = measured
```
HCO3 = calculated
pH = 6.1 + log([HCO3] / [ 0.03 x PCO2 ])
251
% dead space (equation)
= (PaCO2 - EtCO2) / PaCO2
252
Fxn of 5HT3 and 5HT4 receptors
Serotonergic drugs = ~95% of body's serotonin (5-HT) is stored in the GI tract
5HT3 receptor activates extrinsic sensory nerves and is responsible for the sensation of nausea and induction of vomiting from visceral hypersensitivity
5HT4 receptor --> increases the presynaptic release of acetylcholine --> propulsive peristaltic and secretory refuels (cisapride vs metoclopramide)
253
How can we use % physiologic dead space as a weaning tool?
= (PaCO2 / EtCO2) / PaCO2
<= 0.5 --> more likely to be extubated
> 0.65 --> less likely to be extubated
254
What is the normal amount of dead space
30%
255
Describe the diving reflex
face contacts cold water
--> reflex mediated by trigeminal nerve
--> impulses to CNs --> decrease HR and increase BP
(shunts blood to cerebral and coronary circulation)
**reflex protects brain from hypoxia-induced injury**
256
How do you calculate MAP
DAP - {(SAP-DAP) / 3}
257
List arterial vasodilators used in CHF
Hydralazine
Amlodopine
Nitroprusside
Dopamine/Dobutamine
258
What are the 4 different types of immune reactions?
```
I = Immediated (IgE)
II = Cytotoxic (IgM, IgG)
III = Immune complex (IgM, IgG)
IV = Delayed hypersensitivity (T cell dependent)
```
259
Equations to calculate dynamic and static compliance
Dynamic
= TV / (PIP - PEEP)
Static
= TV (Pplat - PEEP)
260
What are the counter regulatory hormones?
**fxn to increase gluconeogenesis and antagonize insulin**
Epinephrine
Glucagon
Cortisol
Growth hormone
261
List medications commonly associated with QRS prolongation due to impaired Na channel influx
```
TCAs
Carbamezapine
Diphenhydramine
Quinidine
Procainamide
Amatadine
```
**slow Na channel influx in phase 0 --> prolong QRS and QT complexes**
262
How does hypo and hypercapnia affect cerebral blood flow?
Hypocapnia --> vasoconstriction
Hypercapnia --> vasodilation
263
Define coronary perfusion pressure and cerebral perfusion pressure
Coronary perfusion pressure = Aortic diastolic pressure - right atrial diastolic pressure
Cerebral perfusion pressure = MAP - ICP
264
Excitatory and inhibitory neurotransmitters in GI motility
Excitatory - Ach (main), substances P
Inhibitory - NO, VIP, ATP
265
Ach acts on which receptor to promote GI contraction?
Ach promotes contraction through muscularies type-2 receptors on the smooth muscle cell
**but it can also stimulate the release of NO --> causing smooth muscle relaxation**
266
How do you calculate INR
PTpatient / PTnormal
| normal is 0.9 to 1.7
267
How do you calculate corrected chloride?
Corrected Cl = measured Cl * (normal Na / measured Na)
268
Define inotropy, chronotropy, lusitropy, and dromotropy
Inotropy = force of contraction (ventricular contractility)
Chronotropy = heart rate (firing of the SA node)
Lusitropy = cardiac muscle relaxation
Dromotropy = conduction velocity through the AV node
269
Explain the cytological difference between iatrogenic hemorrhage and true hemorrhage
Iatrogenic = presence of platelets
True hemorrhage = lack of clotting, absence of platelets, evidence of erythrophagocytosis
270
What is the equation of motion?
Muscle pressure + ventilator pressure
= TV / compliance + (resistance x flow)
271
MOA of aminocaproic acid and tranexamic acid
lysine analogues
block binding/activation of plasminogen
decrease fibrinolysis
272
TFPI MOA
inhibits fVIIa (TF) and fXa
273
Fibrinogen binding site on platelet
to alpha2b Beta3 receptor
| formerly glycoprotein IIbIIIa
274
Cryoprecipatate vs CryoPoor
Cryoprecipitate - VIII, fibrinogen
CryoPoor - 2, 7, 9, 10, 11
275
Why are critically ill patients hypocoaguable?
Dilution
Hypothermia
Acidosis
276
tPA MOA
convert plasminogen to plasmin
--> degrades fibrin into soluble degradation products
277
Briefly describe cell-based coagulation
Initiation - vascular damage / inflammation enables contact btwn plasma and TF-bearing cells
**fVII binds to TF -> fVIIa -> thrombin-> activates platelets
Amplification - platelets are activated and have activated V and VIII
Propagation - lg scale thrombin generation --> fibrin
278
Bromethalin MOA
uncoupling of oxidative phosphorylation w resultant decrease in ATP production
-->. results in ATP dependent transport pumps not functioning (Na/K pumps)
- -> build-up of intracellular Na -->. H20 into cells
- -> cerebral edema and increased ICP
279
Calculate the fractional excretion of a solute
Fix = (Ux x Pcr) / (Ucr x Px)
280
Calculate creatinine clearance
= (Ucreatinine x urine flow) / Plasma creatinine
281
Calculate fractional shortening
LVIDd - LVIDs / LVIDd
Normal 30-45% dogs
40% cats
282
Define base deficit
amount of base that must be added to titrate 1 L of arterial blood to a pH of 7.4 at 37 C and PaCO2 of 40 mmHg
283
Critical DO2
at O2ER 70%
284
Calculate the oxygen extraction ratio
= VO2 / DO2
= (CaO2 - CmvO2) / CaO2
**normal is about 20% of blood delivered to the systemic capillaries is taken up by the tissues**
285
Equation for coronary perfusion pressure
CoPP = diastolic aortic pressure - right atrial diastolic pressure
286
Coronary perfusion pressure associated with ROSC?
> 15 mmHg during CPCR
287
Stroke index equation
= CI / HR
288
SVRI equation
= (MAP - CVP) / CI
289
O2 delivery equation
= CI x CaO2
290
O2 utilization or uptake equation
= CI x (CaO2 - CvO2)
291
Vascular resistance equations
R = (Pin - Pout) / Q
SVR = (MAP-RAP) / CO
PVR = (PAP-LAP) / CO
292
Henderson Hasselbach equation
pH = 6.1 + log10(HCO3 / 0.03*pCO2)
293
List the diuretics and where they act - including the channel
Furosemide - loop diuretic - LOH Na/K/2Cl channel
Thiazides - early distal tubule - Na/Cl channel
Osmotic diuretics - Mannitol - throughout - mainly LOH
Aldosterone sparing diuretic (spironolactone) - late distal tubule, collecting duct
Carbonic anhydrides inhibitors (acetazolamide) - proximal tubule and late distal tubule
294
Diethylstilbestrol
synthetic estrogen
increases urethral smooth muscle tone
295
Diazepam MOA
GABA A receptor agonist
GABA A receptors are ligand- gated CL-sensitive ion channels that are activated by GABA
--> increase in Cl conduction across the cell membrane --> cell hyperpolarization --> cells are less excitable and action potential development is limited
296
Components of the ATT score?
(1) perfusion
(2) skeletal
(3) muscle/eye/integument
(4) cardiovasular
(5) respiratory
(6) neurologic
Score 0-3
3 = severe injury
297
MOA of cyclosporine
blocks T cell function through inhibition of calcipeurin
decreased lymphocyte proliferatin
inhibits cytokine production
inhibits macrophage function
298
MOA azathioprine
purine analogue - inhibits cellular proliferation, lymphocyte activation, suppresses Ig production
cytotoxic antimetabolite converted to 6-mecaptopuriae
299
3 fates of glucose in the brain
(1) glycolysis to pyruvate
(2) pentose phosphate pathway (DNA or RNA synthesis)
(3) glycogenolysis under PK or PFK
300
SVR equation
= (MAP-CVP / Q) *80
301
Describe vasoconstriciotn/dilation in brain
Increased PaCO2 = vasodilation
Decreased PaO2 = 50-60 vasodilates
Increased cerebral metabolic rate = increased cerebral blood flow
302
What is the primary determinant of cardiac resting membrane potential?
K (intracellular to extracellular K ratio)
b/c K channels are mainly open at rest
303
What is normal resting and threshold membrane
resting membrane potential = -90
threshold membrane = - 60
304
CRP
= acute phase protein produced by hepatocytes in response to inflammatory cytokine release (TNF-alpha, IL-B)
*not the ideal marker for diagnosis of sepsis b/c prolonged 1/2 life and lack of specificity between sepsis/SIRS
305
Alfaxalone MOA
synthetic neuroactive steroid
306
5HT3 antagonists
= ondansetron, dolasetron
= competitive blockers of serotonin 5hT3 receptors
- peripherally and centrally CRTZ, MVC
307
Diazepam MOA
act via inhibitory neurotransmitter (GABA)
serotonin antagonism
decreased release/turnover of acetylcholine in CNS
308
Drugs that inhibit P450
= decrease clearance and increase concentration of drug
Fluoroquinolone inhibit clearance of bronchodilator theophylline and increase theophylline [ ] and methylxanthien toxicity
Cimetidine inhibits CYP enzymes, inhibit clearance of B-blockers, theophylline, cyclosporine, chloramphenicol
Erythromycin, phenobarbitals, corticosteroids, inhibit CYP
309
How does oscillemetric measure BP?
cuff inflated until audible sounds decrease - deflated by ~5mmHg and 1st sound = SAP
loads sound = MAP
sound where noise plateaus again = DAP
**calculage SBP and DBP from MAP**
310
Erythromycin MOA
= macrolide antibiotic
MOA: motion receptor agonist
- stimulates cholinergic and noncholinergic
- neuronal pathways that increase motility
**increase gastroesophageal sphincter pressure in dogs and acceleration of colonic transport**
311
Ohm's law
Flow = change in pressure / resistance
312
Thrombin inhibitors
block action of thrombin by blocking the binding site
= think "Rudin" for general names
313
ATT score and mortality link
each 1 point increase in ATT score -> 2.5x higher risk
314
Ketamine MOA
NMDA antagonist (Ca receptor)
decreases presynaptic release of glutamate
interaction w/ opioid receptors (mu/kappa preference) &&nalaxone doesn't antagonize effects
```
antagonist of muscarininc/nicotinic receptors
anticholinergic symptoms (increase HR and bronchodilator)
anesthesia at high doses (inhibit neuronal Na channels)
```
315
List the 2 main antiplatelet drugs and their MOA
Clopidogrel - inhibits P2Y12 receptor , interferì w/ ADP-induced platelet aggregation
Thromboxane A2 - activates GPIIb/IIIa, NSAIDs interfere w/ production of TXA2
316
Factor deficiencies of hemophilia
Hemophilia A= 8
| Hemophilis B= 9
317
Equation for fractional excretion of Na
= NAurine x Creatinine serum / Naserum x Creat urine
* 100
318
MOA of platelet adherence to vessel wall
exposed collagen binds GP1a-IIa
vwf binds GP1b
platelet-platelet adherence and fibrinogen GPIIb IIIa
319
Virchow's triad
blood states, endothelial dysfunction, hyper coagulability
320
Define the respiratory quotent
= volume of CO2 eliminated relative to volume of oxygen absorbed during oxidation
```
Fat = 0.7
Protein = 0.8
Carbs = 1
```
321
Cimetidine MOA
H2 receptor antagonist
Inhibits P450 enzymes
- lessen severity of acetaminophen intoxication
- decrease metabolism of theophylline, lidocaine, metronidazole
322
Domperidone MOA
dopamine antagonist, similar prokinetncs as metoclopramide, but has no cholinergic activity and is not inhibited y atropine
acts on CRTZ
323
What is abnormal automaticity
when pacemaker shifts away from SA node
324
Enhanced/suppressed automaticity
net gain of + ions --> increase steepness of phase 4
325
PVR equation
(PAP - PAOP) / Q. * 80
326
Excitatory vs inhibitory neurotransmitters
Excitatory = glutamate, aspirate, acetylcholine
Inhibitory = GABA
327
What are the reactions of enrofloxacin and theopylline
Enro can increase theophylline plasma [ ] to toxic levels b/c o impaired hepatic clearance of theophylline
328
Cisapride MOA and drugs that inhibit metabolizm
5HT4 agonist
drugs that inhibit metabolism: erythromycin, fluconazole, itraconazole
329
N-acetylcysteine
augments endogenous glutathione stores as it is hydrolyzed to cysteine
used to limit formation of toxic metabolite NAPQI by providing alternate glutathione substrate w/ acetaminophen toxicosis
330
Sotalol MOA
Class II (beta blocker)
Class III (K blocker)
331
Ketoconazole and cyclosporine
use of both drugs results in marked prolongation of the 1/2 life of each drug
both are inhibitors of P-gp and CYP3A
332
MAROPINTANT MOA
NK1 RECPETOR antagonist
- blocks actions of substance P in the area postrena an nucleus solitaries
333
Mycophenolate MOA
inhibits inosine-5' monophosphate dehydrogenase which is needed for purine synthesis
- lymphocytes need this pathway so get inhibition f T and B cell populations
334
Lefluonmide MOA
inhibits enzyme for pyrimidine synthesis
--> suppresses activated T and B cells and prevents proliferation
Inhibits IL-1 and TNF-alpha production
335
Platelets Gp Ib-IX-V
ligand surface bound vWF and thrombin
also for P-selectin on endothelial cell
336
Platelets GP VI
collagen
337
Platelets GP IIb IIIa
principle site for fibrinogen
338
TEG
R = evaluates intrinsic pathway and clot formation
K = measures speed of clot development
MA: represents clot strength
alpha angle: clot formation rate
339
Substances transported by albumin
```
benzodiazepines
cephalosporins
furosemide
NSAIDs
Bilirubin
Copper
```
340
Drugs that induce CYP450
= increase rate of metabolism / clearance of drug
```
Barbiruates (phenobarbitals)
omeprazole
rifampin
grisulvoulfvn
st johns wort
```
341
GP IIb IIIa
binds vWF and fibrinogen
key role in platelet adhesion, aggregation
342
MOA of ways to decrease K
10% Ca gluconate = increase threshold voltage
NaHCO3 = increase extracellular pH --> K moves intracellularly
Dextrose w/ insulin = allows for translocationof K into intracellular space
Terbutaline = stimulates Na/K atlases --> translocation of K into cell
343
Ranitidine
MOA: H2 receptor antagonist
acetylcholinesterase inhibition --> increase amount of acetylcholinesterase available to bind smooth muscle muscarinic cholinergic receptors
344
HES longer vs shorter
= branched polymers of glucose derived from hydrolysis of amylopectin
longer 1/2 life: larger molecular weight, higher degree of substitutions, higher C2:C6 ratio
345
Frozen plasma
plasma that is frozen > 8 hours or is FFP that has been in the freezer for a year
Plasma proteins II, VII, IX, X
346
Cryoprecipitate
fibrinogen
fibronectin
factor VIII
vwf
347
Categories of SSTIs
(1) polymicrobial (mixed anaerobes and aerobes, usually isolate 4+ organisms)
(2) mono microbial (beta-hemolytic strep)
(3) mono microbial gram negative
(4) fungal infections
348
how much dextrose does D5W contain
5 grams of dextrose per 100 ml of solution
5%
349
Beta blockers MOA
inhibit the current I(f) (an important pacemaker current)
- inhibit inward Ca current
slows AV nodal conduction in supra ventricular tachyarrhythmias
- slows sinus nodal discharge rate
- suppress ventricular tachyarrhytmias
ex. atenolol and esmolol
350
Class III anti-arrhythmics
block K channels
ex. stall, amiodarone
351
Digoxin MOA
slow sinus node discharge rate
prolong AV nodal refraction's
--> slow AV nodal conduction
352
LMWH vs unfractionaed heparin MOA
unfractionated heparin acts w/ antithrombin to inhibit the activity of factors IIa and Xa
LMWH - only Xa
353
Streprokinase MOA
combines w/ plasminogen to form an activator complex that converts plasminogen to plasmin (** = nonspecific plasmin activator)
**Plasmin degrades fibrin, fibrinogen, plasminogen, coagulation factors and streptokinase
Produced by streptococci --> can lead to antigenic stimulation
354
Tissue plasminogen activator
primary activator of plasmin --> degrades fibrin
355
Antifibrinolytic drugs
= aminocaproic acid and tranexamic acid
they reversibly block the lysine-binding site on plasminogen (which is essential for binding to fibrin)
356
Electrolyte changes with acute tumor lysis syndrome
Decrease Ca and increased K, Phos
357
Explain MOA of V2 receptors and AVP
V2 receptors on the basolateral membrane of the distal tubule and in the principal cells of the cortical and medullary collecting duct
Increased cAMP --> fusion of aquaporin-2 bearing vesicles w/ the apical plasma membrane
358
Bromethalin intoxication
cerebral edema and severe neurologic signs
toxic effects due to uncoupling of oxidative phosphorylation w/ resultant decrease in ATP production
--> decreased energy leads to nonfunctioning Na/K ATPase and increased intracellular Na --> water molecules into cells --> cerebral edema
359
Toxin of black widow spicers
alpha-latrotwxin
stimulates end plate action potential, forming an open channel for monovalent cation exchange
depolarization --> Ca and release of neurotransmitters (acetylcholine and NE) and inhibits their reuptake
later blocks neurotransmission, likely due to depletion of synaptic vesicle content at the NMJ
360
Beta-blockers MOA
decrease transmembrane Ca flow by decrease cAMP synthesis
--> decrease atrial and ventricular contractility
--> decrease HR, slow speed of excitation through AV nodes and ventricles
361
Type of Beta Blockers
B1 and B2 = sotalol and propranolol
B1 = atenolol and esmolol
362
Glucagon use with B blocker and Ca channel overdose
Glucagon secreted from pancreatic isolets
- binds to receptors distinct from L-type Ca channels and adrenergic receptors
--> stimulates cAMP --> Ca influx and release of Ca from SR
Glucagon has dromotropic, inotropic and chronotropic
363
MOA that NCPE occurs w/ Ca-channel blockers
inhibits alveolar fluid clearance by interfering w/ trans epithelial Na and K transport
364
Cimetidine P450 effects
inhibits P450
365
MOA of bee venom
Phospholipase A2 major allergen
Mellitin causes pain
Hyaluronidase disrupts collagen
Apamin is neurtoxic
Adolapin inhibits prostaglandin synthesis
Mas cell degranulation
366
Phenothiazines (acepromazine) MOA sedation
blocks postsynaptic dopamine and alpha1 adrenergic receptors
367
Thiazode diuretics
inhibit NaCl cotransporter on apical membrane of distal tubule
368
Hydralazine MOA
arteriolar dilator
Na retention and reflex tachycardia may occur
369
eX of arterial vasodilators
Nitroprusside
| Hydralazine
370
Drugs that inhibit AVP
glucocorticoids
low-dose opioids
Atrial natriuretic factor
GABA
371
Intrinsic or extrinsic pathways for heparin and warfarin
Warfarin - extrinsic
Heparin - intrinsic
372
MOA of aminoglycocoides
impair protein synthesis by binding to 30s ribosomal subunit
373
MOA fluroquinolones
inhibit DNA gyrase, topoisomerase
374
MOA macrolides
bind to 50s ribosomal subunit and suppress RNA synthesis
375
MOA chloramphenicol
inhibits protein synthesis in bacteria acts on 50s ribosomal unit
376
MOA spironolactone
aldosterone antagonist
-blocks effects of aldosterone on renal distal convoluted tubule and collecting duct --> decreased Na reabsorption and decreased K excretion
377
Albumin fxns
COP
wound healing
coagulation
scavenging free radicals
carrier for multiple substrates
**also a weak buffer by binding H ions**
378
Hypotonic fluid loss
DI or excessive panting
379
Ketones not deterred on UA
nitroprusside reagent in urine dipstick reacts w/ acetoacetate not B-hydroxybutyrate which is dominant ketone body in DKA
**measurement of serum beta-hydroxybutyrate is more sensitive than measurement of urine in ketones**
380
How do plasma proteins act as buffers
plasma proteins are made up of amino acids that act as weak acids and represent a buffer system in the plasma in most species
albumin - major determinant of total weak acid concentration
**if plasma proteins increase, more o these weak amino acids the can generate/donate protons and H+ will increase**
381
Name the counter regulatory hormones and which 2 elevate w/ in minutes?
Glucagon
Epinephrine
Cortisol
Growth hormone
Glucagon and EPI are unregulated in minutes
Growth hormone and cortisol take a few hours
382
Difference in osmolality and tonicity?
Osmolality = all osmoses in solution
Tonicity = effective osmoles
383
Describe the MOA for hypokalemia in DKA
(1) K binds to ketoacids
(2) decreased dietary intake
(3) insulin therapy worsens and drives K intracellularly
(4) loss - vomiting, osmotic diuresis
384
Define molar substitution
average # of hydroxyetyl residues per glucose subunit defines the MS
**with higher substitution associated w/ delayed enzymatic breakdown**
385
Increase in plasma osmolality is detected by _______ and result in ________
supra and paraventricular nuclei in hypothalamus
--> release of ADH (which increases water reabsorption by renal collecting ducts --> get more concentrated urine
386
How do hemoglobin-based oxygen carriers result in increased BP?
supports COP b/c has high COP (42)
(1) scavenges NO
(2) blockade of nitric oxide
(3) increased circulating [ ] of endothelial
387
Explain the chloride shift and when it occurs
w/ acute respiratory acidosis w/in 5-10 mins you see an increase in HCO3
b/c chloride enters the RBC in exchange for HCO3
388
How much does 4 ml/kg ov hypertonic saline expand ECF space
by 12-16 ml/kg
389
Name 3 natural colloids
albumin
fibrinogen
globulin
390
What is associated w/ a longer half life for HES?
Higher/larger molecular weight
Higher degree of substitusions
Higher C2:C6 ratio
391
Where is the thirst center located?
supraoptic and prep-tic nuclei in anteroventral region of 3rd ventricle in the brain
produces sensation of thirst
Increased plasma osmolality and decreased baroreceptor stretch stimulate thirst center
392
Define molar substitution
the average number of hydroxyetyl residues per glucose unit
Hetastarch 0.7
Hexastarth 0.6
Pentastarch 0.5
Tetrastart (0.4). = vetstarch
393
List the coag factors in the main blood/plasma products
FFP = all
FP = loses liable clotting factors (5, 8) has 2, 7, 9, 10, and plasma proteins
Cryopreciptate = 8, vwf, fibrinogen
Cryosupernatant = 2, 7, 9, 10, 11, 12, albumin, globulin, antithrombin, protein and S
394
HES affects on coagulation
Decreased FVIII and vwf --> decreased clot firmness
Profibrinolytic activity
Platelet dysfunction
395
Why should you not bolus hypotonic fluids
ineffective at expanding intravascular volume
may lead to life-threatening cerebral edema (rapid IV bolus --> decrease plasma and ECF osmolality b/c of Na level --> h2- shifts from ECT to ICF
396
Why do you get PU/PD w/ pyometra?
E. coli LPS endotoxin causes insensitivity to ADH at the distal convoluted tubule and collecting ducts
--> impairs concentrating ability which results in isosthenuria or hyposthenuria
397
How are the buffers alkalinizing in IVF
metabolism of these buffers consumes H ions --> alkalinizing effects
398
GPIIb/IIIa
binds fibrinogen and vwf
**is coated w/ use of HES - so decreased binding ability**
399
How are Mg and insulin fxn intertwined?
Mg is a cofactor for insulin release and fxn and maintenance of appropriate cellular sensitivity to insulin
Insulin deficiency may result from decreased Mg
400
Dilutional acidosis as explained by stewart
SID = strong cations - strong anions
**normal is 40-44**
0.9% Nacl --> 154-154 = 0 SID
LRS --> 130+4 - 109 = 28
both have an acidotic effect b/ decrease SID compared to normal but LRS effect is minimal
**albumin is also a weak acid and diluting it out has an alkalinizing effect --> so decreases the effect of a dilution acidosis
401
Atot
= total weak acid concentration
**mainly based on albumin
Atot = 2.43 * (total protein)
402
List biological buffers
Hgb
BOne
Protein
Bicarb (CO2 system)
403
Where are lactate, acetate, and gluconate metabolise
Lactate = liver
Acetate = muscle
Gluconate = **not metabolized, not a buffer**
404
Does metabolism of Norm-R, LRS, or P148 have an acidotic or alkalinizing effect
all alkalinizing b/c of metabolism of buffers (acetate, gluconate, lactate)
**so even through pH of IV fluids acidic, b/c of these buffers --> alkalinizing effect**
405
Free water deficit equation
= ((current Na/normal Na)-1) * 0.6* BW
406
Does MG affect GI motility?
Yes decreased mg--> decreased GI motility
407
Which drugs result in increased Mg
laxatives
antacids
enemas
408
Equation to calculate standard base excess
SBE = 0.93 * (HCO3 * -24.4 + (pH - 7.4))
409
Write the Henderson-hasselbach equation
pH = pK + log (HCO3/H2CO3)
= 6.1 * log (HCO3) + (0.03 * PaCO2)
410
Explain MG absorption
Thicken LOH - 80%
Proximal tubule 5-15%
Distal collecting tubules 5-10%
411
Cause of acute coagulopathy of trauma
Shock w/ tissue hypo perfusion
Sympathoadrenal activatio
Inflammation
412
Growth hormone effects on BG
GH antagonizes the effects of insulin by decreasing peripheral glucose utilization and promoting lipolysis
413
Cortisol effects on BG
increase glucose-facilitating lipolysis and release of amino acids from muscle for glucogenogenesis in the liver
414
Ammended insulin/glucose ratio
AIGR = (insulin*100) / (plasma glucose - 30)
AIGR > 30 suggests insulinoma
use has fallen out of failure as other causes of hypoglycemia can also have a AIGR > 30
415
Glucagon fxn
secreted from pancreatic alpha cellls
acts on liver to stimulate glycogenolysis and gluconeogenesis --> increases hepatic production of glucose
**reduces peripheral glucose utilization**
**transient as insulin counteracts effects**
416
Epi effects on BG
limits insulin secretion
and increases glucagon secretion
417
Corrected Na equation
**for every 100 mg/dl increase in BG --> Na decreases by 1.6**
Na corrected = Na(measured) + 1.6 (measured BG - normal BG / 100)
418
Medullary washout
abolition of medullary hypertonicity gradient
proper fxn of vasopressin and receptors allows water channels to be open in the tubular cells of the collecting duct - passage of water from tubular lumen into interstitial is passive and based on hypertonicity of renal medulla, enabled by renal counter-current mechanism
**if hypertonicity absent, urine will not become concentrated**
Medullary washout occurs (1) fluids extended period
(2) insufficiency solutes (decreased Na, decreased BUN
419
Hypoperfusion effects on coagulation
increased expression of thrombomodulin on surface of endothelial cells
- -> increases activated protein C
- -> inactivates fVIIa and fVa
- -> promotes fibrinolysis through inhibition of plasminogen activator inhibitor -1 (PAI-1)
420
Causes of RAC (resuscitation associated coagulopathy)
Persistent hypothermia, acidosis, hemodilution
--> results in hypofibrinogenemia, platelet dysfunction, thrombocytopenia, and decreased enzymatic activity
421
What is the theory behind damage control resuscitation
prevention of coagulopathy through permissive hypotension, limiting fluids, and delivering higher ratios of plasma and platelets
goal is permissive hypotension to minimize dilution coagulopathy secondary to fluid administration by maintaining a lower systemic blood pressure (MAP 50 instead of 65)
422
Type 1 vs type 2 error
Type 1 error = false positive
Type 2 error = false negative
423
Cushing's response (MOA)
when volume buffering and auto regulation exhausted --> intracranial hypertension results in decreased CBF, cerebral ischemia, and reaccumulation of H
--> stimulates catecholamine release
--> systemic vasoconstriction --> baroreceptors sense hypertension --> vaguely mediated decrease in HRand you get increased BP and decreased HR in response to intracranial hypertension
424
Tetanus (MOA)
= caused by neurotoxins released by clostridium tetani
toxin affects inhibitory interneurons, inhibiting release of glycine and GABA
--> nerves lose inhibitory control
425
Cheyne-stokes breathing
periods of apnea and hyperpnea
**seen w/ diffuse cerebral or thalamic disease and metabolic encephalopathies**
426
Central neurogenic hyperventilation
persistent hyperventilation that may result in respiratory alkalosis
**midbrain lesion**
427
Apneusis
= breathing pauses for a period at full inspiration
**pontine lesion**
428
Bilateral miosis
metabolic encephalopathies
-OR- diffuse midbrain compression and increased ICP
may precede mydriatic unresponsive pupils
429
Irregular or "ataxic" breathing
irregular frequency and depth of respiration the typically precedes complete apnea
**lower pons/medulla**
430
Physiologic nystagmus or "doll's eye" reflex
conjugate eye movements in response in response to vestibular input (turning head side to side)
loss - lesion medial longitudinal fascicles in the pons and midbrain. (CN III, IV, VI)
431
Ammonia
produced in intestinal tract as end product of amino acid, purine, and amine breakdown by bacteria, the metabolism of glutamine by enterocytes, and breakdown of urea by bacterial urease
then absorbed into portal blood --> converted to urea or glutamine in normal liver
432
MOA of lactulose and antibiotics with HE
lactulose minimizes ammonia production and absorption
intestinal bacteria hydrolyze lactulose --> producing organic acids that lower colonic pH
acidification traps ammonia in its NH4+ form preventing absorption by nonionic diffusion and also resulting in net movement of ammonia from blood into bowel lumen
Abx: decreased # of urease-producing bacteria
433
Benzos MOA
GABA agonist --> increased Cl intracellular flux
434
Phenobarbital
Barbiturate that facilitates GABA-ergic activity by prolonging opening of Cl channels
--> inhibits glutamate receptors and voltage-gated Ca channels
435
Keppra MOA
binds to synaptic vesicle protein SV2A
--> decreases release of neurotransmitter into synapse
436
KBr MOA
hyperpolarization of the neuron via the movement of the Br ions intracellularly through Cl channels
437
Respiration is mediated by.....
respiratory centers in the caudal brainstem between midpoint and cervicomedullary junction
