Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Block 9: Cardio, Renal and Resp II > Week 8 (Anesthetics, Transplant, Cardiac Life Support) > Flashcards

Week 8 (Anesthetics, Transplant, Cardiac Life Support) Flashcards

1
Q

Where do inhaled (volatile) anesthetics work?

A

Directly activate GABA-A receptor (allow Cl- to come into cell?) and inhibit nicotinic ACh receptors (which are usually excitatory) –> inhibition

Voltage gated ion channels (Na, K, Ca)

G-proteins

Protein kinase C

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Anesthetic effects

A

Explicit memory: amnesia

Consciousness: inhibition perceptive awareness, unconsciousness

Pain response: immobility to pain

Autonomic system: reflex blunting, autonomic depression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Stages of anesthesia

A

Analgesia

Excitement

Surgical anesthesia

Medullary depression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Minimum alveolar concentration (MAC)

A

Alveolar concentration (%) of an inhalation agent that produces immobility to noxious stimulation in 50% of subjects (humans: skin incision)

Advantages of MAC: short equilibration time, alveolar concentration represents partial pressure of anesthetic in CNS; consistency for given animal group or between species

Measures potency (increased MAC = decreased potency)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Things that affect MAC

A

Temperature: MAC decreases with decreasing body temp (approx 2-5% per degree); people who are colder are more likely to go unconscious

Age: MAC is maximal at 6 months of age and gradually decreases with age (MAC for octogenarian is 50% that of infant); gases become more potent as you age

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

MAC of commonly used gases

A

NO >100%

Desflurane 6-7%

Sevoflurane 2%

Isoflurane 1.4% (most potent)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Speed of induction: uptake and distribution

A

Alveolar partial pressures of gas agents govern partial pressure of gas agents in all other parts of body (including brain)

Two factors primarily affect the rate of rise of alveolar partial pressure: alveolar/inspired relationship (FA/FI); uptake by blood

Inspired gas –> alveolar concentration –> uptake

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What affects rate of rise of alveolar concentration?

A

Increased inspired concentration –> increases rate of rise of alveolar conc

Increased uptake by blood –> decreases rate of rise of alveolar conc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Inspired-alveolar relationship

A

Inspired concentration of the gas

Pulmonary ventilation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Uptake by blood

A

Decreased solubility increases alveolar concentration more rapidly

Increased CO (pulmonary blood flow) decreases alveolar concentration more rapidly

Alveolar-venous partial pressure difference: dependent upon tissue uptake which effects venous partial pressure; increased venous partial pressure decreases A-V partial pressure difference and increases alveolar partial pressure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Elimination

A

Occurs as anesthetics are transferred back from brain to alveolar space and exhaled

Less soluble anesthetics eliminated more rapidly

Duration of exposure: since there is accumulation of anesthetic in less perfused tissues (muscle, fat and skin)

Minute ventilation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What increases alveolar partial pressure of gas?

A

Increased inspired concentration of gas

Increased minute ventilation

Decreased solubility

Decreased CO

Decreased A-V difference (increased venous partial pressure)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Effect of N2O on closed gas spaces

A

Nitrogen 30x less soluble than NO

NO enters airspaces faster than nitrogen leaves so significant enlargement of airspaces

Airspaces include bowel, inner ear, pneumothoraces, air emboli

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Effects of inhaled anesthetics

A

Pulmonary: decrease or same TV, increase or same RR, decrease or same minute ventilation, increase apneic threshold, increase bronchodilation, increase or same airway irritability

Cardiovascular: decrease BP, decrease myocardial function, decrease (NO increases) SVR, increase (NO decreases) HR, increase or same coronary vasodilation

Brain: decrease metabolic rate, increase cerebral blood flow (increased ICP)

Kidney: decrease GFR

Uterus: except N2O, all others are relaxants (good for delivery, bad after because too much bleeding if uterus doesn’t contract again)

Toxicity: no studies have demonstrated mutagenesis, teratogenesis, and carcinogenesis with modern anesthetics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

IV anesthetics

A

Rapid induction of anesthesia

Continuous sedation with infusion

Ex: propofol, ketamine, etomidate, dexmedetomidine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

One compartment model

A

Drug administration –> V1 central compartment –> elimination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Three compartment model

A

Drug administration –> V1 central –> V2 rapid equilibrating compartment or V3 slower equilibrating compartment –> elimination or Ve effect site to elimination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Propofol

A

Most frequently used IV anesthetic

Administered as bolus (induction) or infusion (maintenance)

Metabolized in liver and excreted in kidney, and 20% excreted in lungs

Abuse potential (“milk of amnesia”)

Initial distribution half-life = 1-8 minutes

Slow distribution half-life = 30-60 minutes

Elimination half-life = 4-23 hours

Primary effect is hypnosis (sedation by potentialting GABA-induced Cl by acting on GABA-A); pleasure seeking by increase DA in nucleus accumbens; anti-emetic by decreasing 5HT in area postrema

Minimal analgesia

Decrease ICP, decrease CMRO2

Decrease BP, O2 supply and demand

No predictable change in HR

Bolus decreases RR and TV and can cause apnea (exaggerated by narcotics)

Infusion causes decrease TV and rate with overall decrease in minute ventilation (exaggerated by narcotics)

Induces bronchodilation

Other effects: euphoromimetic, pain on injection, sepsis/infection, anaphylaxis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Ketamine (PCP)

A

Glutamic acid inhibitor at NMDA receptor

Metabolized by liver

Slow distribution half-life = 11-16 min

Elimination half life = 2-3 hours

Unconsciousness and analgesia

Dissociative anesthesia: patients appear to be in cataleptic state with eyes open and many reflexes intact but profound analgesia and amnesia

Some opioid mu receptor activity

Increase ICP, cerebral metabolism, CBF

Increase BP, HR, CO, O2 demand and work, SVR, PVR (central mechanism that enhances SNS to release NE)

No effect on central respiratory drive

Bronchodilator

Increased salivation with possible airway obstruction in children

No pain on injection

Undesirable psychological reactions during awakening (vivid dreaming, extracorporeal experiences and illusions), associated with excitement, confusion, euphoria and/or fear, attenuated by benzos

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Etomidate

A

Imidazole derivative

Half life 3 minute initial redistribution, 29 minute slow distribution half life, 2.9-5.3 hour elimination

Cleared by liver

Hypnosis (GABA agnoist)

After bolus, CMRO2 decreases by 45%, CBF decreases by 34%, net increase in cerebral O2 supply-demand ratio

Reduction in ICP

EEG similar to barbiturates, ultimately burst suppression; increases EEG activity in epileptogenic foci

Minimal cardiovascular effects (and no effect on SNS or baroreceptors)

Respiratory effects: minimal effect on ventilation, ventilatory response to CO2 depressed (leads to brief periods of apnea), doesn’t release histamine, mild pulmonary vasorelaxant effects

Potetial problems: mild decrease in cortisol (not likely relevant), pain on injection, N/V, myoclonus and hiccups

Uses: bolus to induce general anesthesia; useful in pts with compromised CV system; useful in neurosurgical procedures because decreased ICP (?) and good cerebral O2 supply/demand and good CV stability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Summary of clinical uses for IV anesthetics

A

Propofol: short cases, outpatient cases, neurosurgical cases, ophthalmology cases, other cases involving patients with reasonably normal myocardial function (most common agent)

Ketamine: trauma cases with significant hypovolemia/shock, pediatric cases (especially congenital heart with right to left shunt)

Etomidate: cardiac and vascular cases, heart and lung transplant cases, patients with significantly depressed myocardial function, also can be used in neurosurgical cases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Dexmedetomidine

A

Alpha2 agonist but highly selective (more than clonidine)

Sleep-like hypnosis

Minimal effect on respiration

Decreases HR, BP, CO

Becoming increasingly popular to use as infusion in intubated pts in ICU

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Other IV anesthetics

A

Barbiturates

Benzodiazepines

Narcotics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Local anesthetic

A

Drugs that produce reversible, conduction blockade of impulses along central and peripheral nervous pathways after regional anesthesia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Cocaine as topical anesthetic

A

Cocaine is vasoconstrictive (less bleeding in surgical area)

ENT uses cocaine for endoscopy of nose/sinuses (can anesthetize mucous membrane)

Only ester that is metabolized in the liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Procaine

A

Local anesthetic

Disadvantages are that it has short duration, systemic toxicity, allergic reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Lidocaine

A

Most widely used cocaine derivative

Inhibits membrane depolarization by blocking conductance of Na+ into cell (reversibly binds and inactivates Na+ channels)

Blocks conduction in peripheral nerves

Action ends when concentration falls below critical minimal level

Rapid onset of action, 2 hr duration (4 hr with epinephrine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Different nerve fibers and which ones are affected by local anesthetics

A

Small C fibers (unmyelinated) and small/medium sized A delta fibers (myelinated) are more sensitive to action of local anesthetics than larger fibers, so patients may be able to feel sensations such as pressure and vibration but not pain

A alpha: muscle spindle

A beta: muscle spindle, touch

A gamma: touch, pressure

A delta: pain

B: preganglionic autonomic

C: pain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Chemical structure of local anesthetics

A

Amine end is hydrophilic

Aromatic end is lipophilic

Linked by intermediate chain: amino amides have amide link and amino esters have ester link

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Amino amides

A

Amides have “i” in first part of word

Lidocaine

Mepivacaine

Prilocaine

Bupivacaine

Etidocaine

Dibucaine

Metabolized by liver and allergic reaction less likely

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Amino esters

A

Esters have no “i” in first part of word

Tetracaine

Procaine

Chloroprocaine

Cocaine

Benzocaine

Metabolized by pseudocholinesterase (a plasma enzyme) and more likely to have allergic reaction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What determines physiologic activity of local anesthetics?

A

Lipid solubility determines potency (increased lipid solubility leads to faster blockade of Na+ channels)

Diffusibility influences speed of action

Protein binding related to duration of action

Percent ionization at physiologic pH: nonionized form diffuses across nerve membrane so means faster onset of action; decreased pH shifts equilibrium toward ionized form which delays onset of action (slower onset of action and less efficetiveness in presence of inflammation which has acidic environment)

Vasodilating properties

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Adjuvants to local anesthetics

A

Bicarbonate: to speed onset of action by increasing pH

Epinephrine: vasoconstrictor so washout of anesthetic slower so longer duration of local anesthetic

Opioids: analgesic so can use less local anesthetic, less motor blockade but same sensory blockade

Hyaluronidase: enzyme that breaks collagen so better tissue penetration of local anesthetic; only used in ophtho cases for retrobulbar block

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Metabolism of local anesthetics

A

Esters metabolized by plasma enzyme pseudocholinesterase and excreted in urine

Exception is cocaine which undergoes metabolism in the liver

PABA is an allergen and a metabolite of hydrolysis by pseudocholinesterase (?)

Amides metabolized in liver and should be used with caution in pts with liver disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Adverse effects of local anesthetics

A

Due to the anesthetic solution:

Systemic toxicity (cardiovascular and CNS)

Allergy (hypersensitivity reaction; hives, swelling)

Neurotoxicity

Tissue irritation

Cardiovascular toxicity: decrease depol of cardiac tissue, decrease conduction velocity; vasodilation leading to hypotension; negative inotropic effect leading to bradycardia, v-fib, asystole

CNS toxicity: light headedness, tinnitus, circumoral numbness, metallic taste, double vision, drowsiness, slurred speech, nystagmus, seizures leading to hypoxia, acidosis, hyperkalemia, respiratory arest

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Progression of symptoms in lidocaine toxicity

A

Numbness of tongue

Lightneadedness

Visual disturbance

Muscular twitching

Unconsciousness

Convulsions

Coma

Respiratory arrest

CVS depression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Special toxicity considerations

A

Benzocaine: methemoglobinemia

2-chloroprocaine: back pain when large doses used and is related to EDTA in preparation

Bupivacaine: CVS toxicity at serum concentration slightly above seizure threshold, cardiac arrest that is resistant to resuscitation (pt needs to be on bypass until bupivacaine wears off)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Techniques for regional anesthesia

A

Topical anesthesia

Local infiltration

IV regional anesthesia: Bier block

Peripheral nerve block: brachial plexus, median nerve

Spinal anesthesia

Epidural anesthesia

Caudal block

39
Q

NTs used in peripheral nervous system

A

Somatic nervous system: Ach acts on nicotinic receptors of motor neurons of skeletal muscle

ANS sympathetic nervous system (thoracolumbar region with ganglia near spinal cord): Ach is preganglionic but NE is primary postganglionic (Epi for adrenal glands and Ach for sweat and salivary glands though)

ANS parasympathetic nervous system (cervicosacral region with ganglia near innervated tissue): Ach only!

40
Q

Ach is the NT for what?

A

Ach is NT for:

All preganglionic parasymp and symp ANS fibers

All postganglionic parasymp ANS fibers

Postganglionic symp fibers to sweat and salivary glands

All somatic motor neurons released at NMJ

41
Q

Nicotinic Ach receptor (nAchR)

A

Receptor is ligand-gated ion channel

2 Ach molecules required to bind 2 alpha subunits to open Na/K ion channel

42
Q

Muscarinic Ach receptor (mAchR)

A

G protein coupled receptor

Ach is ligand

43
Q

Nicotinic vs muscarinic receptors

A

Nicotinic receptors use ion gated mechanism for signaling; sufficient ligands cause ion channel to open; diffusion of Na and K across receptor causes depolarization, the end-plate potential, that opens voltage-gated Na+ channels which allows for firing of AP and potentially muscular contraction; primary receptors of autonomic ganglia and sole Ach receptors at NMJ

Muscarinic receptors use intracellular G proteins as signaling mechanism; ligand (Ach) binds receptor which has 7 transmembrane regions; receptor bound to intracellular G proteins which activate other ionic channels via second messenger cascade; found at some autonomic ganglia and effector organs

44
Q

Botulinum toxin

A

Degrades synaptobrevin (SNARE protein) preventing Ach containing vesicles from fusing with presynaptic plasma membrane –> blockade of Ach release –> flaccidity (“floppy baby”)

In case of poisoning, treatment is antitoxin and supportive care (mechanical ventilation)

Medical therapies include treatment of migraines, spasticity, cosmetics, etc

45
Q

Summary of Ach at the NMJ

A

Ach released from presynaptic nerve terminal into synaptic cleft after nerve impulse

Ach then binds 2 alpha subunits of nAchR opening the ion channel to Na+ and K+

When sufficient nAchRs are activated, transmembrane potential increases from -90 mv to -45 mv and AP is propagated over skeletal muscle surface causing contraction

46
Q

Use of neuromuscular blockade in anesthesiology

A

NMB used daily by anesthesiologists to facilitate endotracheal intubation, provide muscle relaxation as needed for intraabdominal, orthopedic, laparoscopic and delicate surgeries

47
Q

Succinylcholine

A

Depolarizing neuromuscular blocker

Structurally similar to Ach (competitive agonist) and binds 2 alpha subunits of nicotinic receptor to open the channel

Rapid (<60 sec) depolarization of muscle cells causes fasciculations followed by flaccid paralysis

Use when rapid and/or brief paralysis desired (rapid endotracheal intubation for patients at risk for pulmonary aspiration, for pts with potentially difficult ET intubation, relaxation for very short procedures such as direct larygoscopy/biopsy)

Remains bound for several minutes because NOT broken down by acetylcholinesterase; diffuses away from motor end plate and quickly degraded into acetic acid and choline by pseudocholinesterase (which is NOT found at NMJ)

Muscle function usually returns after 5-10 min

Side effects: hyperkalemia due to depolarization (more in pts with recent burns, renal failure, neuro/muscular disorders), myalgias, increased ICP, intragastric pressure, ophthalmic pressure; may cause prolonged paralysis if pt has atypical pseudocholinesterase; malignant hyperthermia

48
Q

Nondepolarizing neuromuscular blockers (NDMBs)

A

Everything else other than succinylcholine!!

Quarternary ammonium compounds with structures similar to Ach

Bind selective alpha subunits of nicotinic receptors

Bulky molecules bind nAchR and act as competitive antagonists to prevent depolarization

Reversal due to slow release into NMJ and then hepatic/biliary and/or renal metabolism

49
Q

Two classes of NDMBs

A

Benzylisoquinolines: curare derivatives including d-tubocurare, atracurium, cisatracurium

Aminosteroids: pancuronium, vecuronium, rocuronium

50
Q

When do you see the effect of NDMBs?

A

No evidence of NM blockade when even 70% of nAchR are blocked!

Once 80-90% of nAchRs are blocked then NM transmission fails

This margin of safety essential in modern anesthesia and is basis for monitoring NM blockade in OR

51
Q

Short acting NDMBs

A

Mivacurium: duration 12-20 min; like succinylcholine metabolized by pseudocholinesterase; but discontinued by manufacturer

52
Q

Intermediate acting NDMBs

A

Cisatracurium: duration 40-75 min; metabolized by Hofman elimination (pH and temp dependent enzymatic degradation NOT organ dependent; good for pts with liver and kidney disease)

Vecuronium: duration 45-90 min; primarily hepatic/biliary but some renal excretion

Rocuronium: like succinylcholine, rapid onset makes appropriate for rapid intubation; duration 35-75 min; primarily hepatic/biliary but some renal excretion

53
Q

Long-acting NDMBs

A

Pancuronium: duration 60-120 min; atypically increases HR by vagal antagonism at cardiac receptors; long-acting NDMBs with primarily renal excretion

54
Q

Side effects of NDMBs

A

Histamine release by atracurium, pancuronium, mivacurium (and morphine!) can cause bronchospasm, flushing, peripheral vasodilation (avoid in severe asthmatics, septic and other susceptible pts)

Allergic reactions can cause anaphylaxis

55
Q

What happens with NDMBs when surgery ends?

A

Problem: residual weakness at end of surgery may prevent adequate spontaneous ventilation

Solution: reverse the paralysis by increasing amount of Ach at NMJ (neostigmine) to competitively beat out NDMB and cause muscle contractions

56
Q

Reversal of NM blockade

A

AchEIs reversibly bind and inactivate AchE in NM junction

Used to increase level of Ach in NMJ to compete with NDMBs for binding sites, thereby reversing NDMB paralysis

57
Q

Problem with NM blockade reversal

A

Ach is also increased at MUSCARINIC receptors!

SLUDGE

Antimuscarinic (atropine) agents must be used to block effects of Ach and avoid cholinergic effects!

58
Q

Neostigmine

A

Reversibly inhibits AchE to allow Ach to remain elevated to stimulate nicotinic and muscarinic receptors

Most commonly used reversal agent in OR

Weak nAchR agonist so excess dosing can itself cause weakness

Also inhibits pseudocholinesterase activity, so NEVER give succinylcholine after administering neostigmine

59
Q

Edrophonium

A

Reversible AchEI

Rapid onset only 1-2 min, lasts >1hr only at higher doses

Less than 10% as potent as neostignime

Used to diagnose myasthenia gravis: if strength improves after giving edrophonium it means Ach levels got high enough to overcome Ach receptor antibodies, leading to resumption of stimulation at NMJ

60
Q

Pyridiostigmine

A

Reversible AchEI

20% as potent at neostigmine

Limited inhibition of pseudocholinesterase

Used to treat myasthenia gravis

61
Q

Physostigmine (“antilirium”)

A

Tertiary amine

Only AchEI that crosses BBB

Used to treat CNS anticholinergic toxicity and for antagonism of volatile anesthetic effects especially in patients with Alzheimer’s disease

62
Q

Irreversible AchEIs

A

Organophosphates

Form very stable bonds to enzyme AchE –> increased Ach

Used in ophthalmology to induce miosis and thereby decrease intraocular pressure

Key ingredient in pesticides

Acute treatment of organophosphate poisoning is with anticholinergic agent atropine but definitive treatment is pralidoxime (must be given before “aging” occurs though)

63
Q

What happens even if you give an appropriate dose of neostigmine for reversal of NM blockade?

A

Inhibition of AchE causes increased Ach which causes increased muscle contractility but ALSO cholinergic crisis (SLUDGE = salivation, lacrimation, urination, defecation, GI upset/hypermotility, emesis) and bradycardia

Excessive dosing can exacerbate weakness

64
Q

Preventing adverse reaction to AchEIs

A

Pretreat with an anticholinergic agent to act at muscarinic receptors

Ex: glycopyrrolate, atropine

65
Q

Anticholinergics/antimuscarinics

A

Atropine: fast onset, shorter duration, crosses BBB, used in tx of bradycardia and as part of ACLS

Glycopyrrolate: intermediate onset, longer duration, does NOT cross BBB, may also be used to counteract bradycardia (induced by surgical stimulation of parasymp nervous system)

66
Q

Pralidoxime

A

Antidote for AchEIs because reactivates inhibited AchE

Treat organophosphate exposure

Helps prevent phosphorylation by organophosphate and helps reactivate AchE

Also used to treat patients exposed to nerve gas or with OD of pyridostigmine (cholinergic crisis) in myasthenia gravis

67
Q

Reversal agent/anticholinergic combinations in anesthesia

A

Safe and effective reversal is based on speed of onset and duration of action fo drugs used

Neostigmine/glycopyrrolate

Edrophonium/atropine

Pyridiostigmine/glycopyrrolate

Physostigmine/not applicable

68
Q

Sugammadex

A

Novel NMB reversal agent

Negatively charged cyclodextrin molecule that reverses NMB by electrostatically binding aminosteroid nondepolarizing agents

Most avidly encapsulates Rocuronium, less avidly binds vecuronium and no binding of benzylisoquinolines

Binding creates concentration gradient favoring release of rocuronium fron nAchR

Equal or faster recovery time after rocuronium compared with succinylcholine

Overcomes problem of inability to achieve timely/complete NMB reversal and complications by relying on Ach

69
Q

Why are living donor transplants better than deceased donor transplants?

A

Because living donor kidneys are healthier–they’re alive!

NOT because of matching

70
Q

Benefits of kidney transplant

A

Transplant doubles anticipated lifespan of patient waiting for transplant

Life-prolonging, and quality-of-life-enhancing

71
Q

Causes of death of people waiting for kidney transplant

A

Diabetes mellitus

glomerulonephritis

Hypertension

Other

Annual death rate overall is 6.3%

72
Q

Types of transplant rejection

A

Hyperacute rejection (antibody-mediated)

Acute rejection (cell-mediated, antibody-mediated, vascular rejection)

Chronic rejection

Chronic allograft nephropathy (CAN)

73
Q

3 signal hypothesis of how body responds to antigen

A

Signal 1: APC presents antigen to T cell receptor (“kiss”)

Signal 2: Costimulation by B7 on APC to CD28 on T cell (“hug”); after 2 signals, calcineurin (phosphatase enzyme) dephosphorylates NFAT so NFAT can now get into the nucleus and cause transcription of IL-2 and CD25 –>

Signal 3: self-proliferation signal

74
Q

Cyclosporin and tacrolimus

A

Calcineurin inhibitors

Block the dephosphorylation of NFAT so NFAT cannot get into the nucleus to cause transcription of IL-2 and CD25 –> no signal 3 to cause proliferation of T cell

Slow down process of responding to foreign antigen

Note: don’t have to tweak immune system THAT much, just cut calcineurin activity by 50% and this is enough

75
Q

Belatacept

A

CTLA-4 Ig

Like abatacept in RA

Blocks costimulatory molecule (B7) from interacting with counterpart on T cell

76
Q

Basiliximab

A

Mab to CD25 receptor (the receptor for IL-2) on T cells

Blocks signal 3 so T cell cannot proliferate

77
Q

Sirolimus/everolimus

A

AKA Rapamycin

Blocks mTOR so cannot do cell division

78
Q

Syndromes of calcineurin inhibitor toxicity

A

Prolonged DGF

Acute reversible decrease in GFR (due to vasoconstriction caused by calcineurin)

Post-transplant TTP

Chronic CI toxicity

Electrolyte disturbance

79
Q

Why do non-renal transplant recipients develop CKD?

A

Because any transplant causes fibrosis in some way

20% of non-renal transplant recipients become candidates for renal transplant

80
Q

Indications for heart transplant

A

Intractable angina

Refractory heart failure

Uncontrolled ventricular arrhythmias

81
Q

Medications as alternative to heart transplant to improve survival

A

Baseline 5-year survival is 40% but with these meds, can raise that to 75%

ACEI

Beta blocker

Aldosterone antagonist

ICD

82
Q

Absolute and relative contraindications to heart transplant

A

Absolute contraindications:

Active malignancy

Active infection

Obesity with BMI > 35

Active substance abuse

Noncompliance

Lack of social support

Relative contraindication:

Diabetes with end-organ dz

Pulmonary HTN

Age > 70

Renal failure

Cerebrovascular/peripheral vascular disease

Cirrhosis

Pulmonary disease

83
Q

Status waiting for a heart transplant

A

Status 1A (days): PA cath + 2 drips; VAD < 30d; IABP or ventilator, exceptions

Status 1B (weeks): 1 inotrope; VAD > 30d

Status 2 (months): everyone else

Longer wait time for larger people and blood type O because just harder to find

84
Q

Mortality after heart transplant

A

Biggest mortality in first year is infection and rejection (only 10% of pts)

After that, conditional half life is 15 years

Cardiac allograft vasculopathy and malignancy more common in year 2 and beyond

85
Q

Significance of the fact that the transplanted heart is denervated

A

No afferents so no angina

No efferents so no vaual input so higher resting HR and rely on circulating epi and NE from adrenal during exercise

More exaggerated orthostatic response because loss of feedback regulation (baroreceptor reflex, RAAS)

Increased receptor density so more sensitive to circulating epi, NE

86
Q

Medications that have no effect or exaggerated effect in heart transplant

A

No effect: atropine, digoxin (because no vagus nerve)

Exaggerated effect: adenosine, beta agonists, beta blockers (because more alpha and beta receptors)

87
Q

Endomyocardial biopsy for rejection surveillance

A

Looking for cellular and humoral rejection

Only care about moderate and severe to treat

Treatment of rejection depends on whether pt is asymptomatic, reduced EF or in heart failure/shock

88
Q

Transplant coronary artery disease

A

Asymptomatic (denervation), fagitue, reduced EF

Panvascular disease, distal pruning

Rapid progression

Concentric lesions

Generally lipid poor, fibrointimal proliferation

89
Q

Management of transplant coronary artery disease

A

Diagnosis: surveillance angiograms, IVUS (not standard)

Prevention: aspirin, pravastatin (doesn’t interact with tacrolimus), vitamin C and E, sirolimus

Treatment: PCI but doesn’t work that well and pts usually need second transplant (TCAD is most common indication for second transplant)

90
Q

How long do heart transplants usually last?

A

10-15 years

91
Q

Indications for lung transplant

A

CF

Idiopathic pulmonary fibrosis (IPF)

COPD

Alpha 1 antitrypsin deficiency

PPH

92
Q

5 year survival rate for lung transplant

A
93
Q

Should we give induction immunosuppression at time of lung transplant?

A

No evidence that it makes any difference in terms of survival, but we do it at UCLA anyway

94
Q

Post lung transplant morbidity

A

Infection biggest problem in first 30 days (lung exposed to outside environment…)

Hypertension

Renal dysfunction

Hyperlipidemia

Diabetes

Bronchiolitis obliterans syndrome (chronic rejection after transplant; is progressive obstructive just like emphysema and is biggest cause of death more than 1 year after transplant; at 5 years, 50% of pts have this)

Skin cancer (squamous cell carcinoma) is problem!

Block 9: Cardio, Renal and Resp II (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions