cyanosis pathophysiology rounds gideon daniel, dvm internal medicine resident 8/22/13
TRANSCRIPT
Cyanosis Pathophysiology rounds
Gideon Daniel, DVM Internal medicine resident
8/22/13
Objectives
O2 transport
Selected disease processes Shock Methemoglobinemia Smoke inhalation Cyanide Carbon monoxide
Cyanosis
Result of desaturation of Hgb Central (abnormal pulmonary function) Peripheral
Takes about 5 g/dL of unoxygenated hgb to manifest cyanosis
“should invoke a feeling of panic and institution of aggressive oxygen, ventilation or fluid therapy”
O2 transport
Ventilation
Pulmonary gas exchange
O2 interaction with hemoglobin (hgb)
O2 delivery to tissue
Extraction of O2 at the tissue
Ventilation
Mechanical process that causes gas to flow into and out of the lungs
VT = VA + VD
VT : total ventilation
VA : alveolar ventilation
VD : dead space ventilation
PCO2 (arterial CO2 tension): primary driving force for ventilation PCO2 = VCO2/ VA x K
VCO2 – total volume of CO2 produced by metabolism
Diffusion
D: Diffusion rate
ΔP: partial pressure difference
A: cross-sectional area of the pathway
S: solubility of the gas
D: distance of diffusion
MW: molecular weight of the gas
Take home message: rate of transfer proportional to tissue area and partial pressure of difference and inversely related to thickness Ex: CO2 diffuses 20x more rapidly than O2
Inspired Gas
Warmed and saturated with water vapor (in trachea) PH20 : 47mmHg at normal body temp (37 C)
PIO2 (partial pressure of inspired oxygen) PIO2 = (PB – PH20) x FIO2
= (760-47) x 0.21
= 150mmHg
Alveolar Gas concentration
Less than inspired air in trachea Due to addition of CO2 from pulmonary capillary
blood
Estimated form alveolar gas equation PAO2 = PIO2 – PaCo2/ R
R= Respiratory quotient = 0.8 Normal: 150 – (40/0.8) = 100mmHg
Pulmonary gas exchange
Impaired when PaO2 < PAo2
Degree can be quantified by calculating alveolar-arterial O2 (PAO2 – PaO2 or A-a) gradient Normal < 10mmhg (room air) Short formula: 150-PaCo2 x 1.25 (if using R= 0.8)
PaO2/Fio2 Ratio Normal > 500 mmHg
The “120” Rule Since alveolar O2 and CO2 should ~ 150mmHg
“Up/Down Offset” Method Using reciprocal relationship b/w PaO2 and PaCo2 Assuming PaCo2 40mmHg and PaO2 100mmHg
Causes of hypoxemia
low PIO2
Hypoventilation
R-to-L Shunts**
Diffusion barrier
VQ mismatch
Low PI02
Relatively uncommon
Decrease in barometric pressure (high altitudes)
Improper inhalant anesthetic technique
Hypoventilation
If alveolar ventilation is abnormally low, then PO2 falls and PCO2 rises
CNS depression (disease or drugs- opioids, barbiturates)
Damage to chest wall
High resistance to breathing Obstructive airway disorders Restrictive lung dz
Results in increased arterial and alveolar CO2
Diffusion impairment
When there is inadequate equilibration of O2 tension across the alveoli and capillaries
Relatively infrequent
Due to thickening of alveolar-capillary membrane Diffuse pulmonary interstitial
dz Loss of alveolar or capillary
surface area (vasculitis) Physiology (high cardiac
output during exercise)
Right-to-left shunt
Blood enters arterial system without passing ventilated areas of lungs
Cardiac disease PDA, VSD, ASD, tetralogy of Fallot
Have a decreased PaO2 with a normal or decreased PaCO2 and widened (A-a) O2 gradient FAILS TO IMPROVE WITH O2
PCO2 can be normal d/t hypoxemia increasing respiratory drive
Can be calculated: Qs/Qt = (SC02 – Sao2) / (SC02- SvO2)
> 10% abnormal
VQ mismatch
Clinical approach
O2 content in blood
CaO2 = (1.34 x Hgb x SaO2) + (0.003 x PaO2) 1.34: the amt of oxygen (mL) that each gr of hgb
can hold If it is 100% saturation SaO2- measured or calculated % hgb saturation
with oxygen 0.003 is the solubility of oxygen in plasma Normal in dogs ~20 mL o2/dL
Hemoglobin
The HemoCue for point-of care hemoglobin measurement and packed cell volume estimation in cats. Posner et al JVECC 2005
Hgb measured in clinical pathology laboratory or is estimated from pack cell volume
HemoCue used only 10 uL of blood and is portable and quick
PCV can be estimated by multiplying HgHQ by 3.1
Oxygen binding to hemoglobin
Oxyhemoglobin dissociation curve
SpO2 PaO2
95-99% Normal
90-94% Moderate Hypoxia
<90% Severe Hypoxia
Factors affecting the curve
Summary
Shift to the right (tissue)
Shift to the left (lungs)
Effects Decreases affinity for O2
Increases affinity for O2
P50 Increase Decrease
CO Increase Decrease
H+ Increase Decrease
Temp Increase Decrease
2,3 DPG Increase Decrease• Bohr effect: hgb’s oxygen binding affinity is inversely
related to acidity and Co2 • Haldane effect: deoxygenating blood assists in
carrying CO2
Carried in 3 forms: Dissolved Bicarbonate
CO2 + H20 ⇋ H2Co2 ⇋ H+ ⇋ HCO3-
Carboxyhemoglobin
More linear than O2 dissociation curve
Small differences between arterial and venous CO2 (5mmhg)
Carbon dioxide transport
DO2 and VO2
Oxygen delivery (DO2): mL of o2 delivered to peripheral tissue each min DO2 = CaO2 x CO
= [(1.34 x Hgb x SaO2) + (0.003 x PaO2)] x (HR x SV)
Oxygen consumption (VO2): mL of O2 consumed by the tissue each min Vo2 = (CaO2 – CvO2) x Q
Oxygen extraction ratio (OER)
OER: O2 consumed (VO2)/(DO2) OER = [(SaO2- SvO2)/SaO2] x 100
Normal ~0.2- 0.3
Lowered OER represents improved relations of DO2 to VO2
The “critical” DO2
B: Point at which compensatory mech fail to meet tissue requirements
Below critical point- oxygen extraction falls in proportion to decrease in oxygen delivery and products of anaerobic metabolism start to accumulate in blood
Shock
Definition: inadequate cellular energy production Secondary to poor tissue perfusion decrease in
DO2 in relation to VO2
Decreased DO2 d/t Loss of intravascular volume (hypovolemic) Maldistribution of vascular volume (distributive) Cardiac pump failure Hypoxemia (severe anemia, pulmonary dysfunction,
methemoglobinemia) Other= hypoglycemia, cytopathic
Monitoring oxygen delivery
Indirect indicators pH, HCO3, BE, CO2 gradient, lactate, HR, BP, CVP,
crt, extremity temp, UOP
SvO2 (venous oxygen saturation) Assesses whole body Vo2/Do2 relationship Reflects changes in Cao2, CO, local blood flow, local
VO2, affinity of Hb for O2 Normal: 65-80%
Assessment of Svo2
SvO2- mixed venous O2 saturation Assessed from pulmonary artery
ScvO2- central venous O2 saturation Cr vena caval/RA via central line < 70% indicates tissue hypoxia Can be a surrogate for SvO2
Methemoglobinemia
Hgb with oxidized Fe 3+
Incapable of carrying O2 Increases the affinity for oxygen
in the remaining ferrous Hgb Shifts the curve to the left
High levels (> 20%) can cause cellular hypoxia and shock
May see concurrent heniz bodies
Gives blood a darker brown color and results in dusky cyanotic or chocolate-colored mm
Etiologies
Acetominophen
Topical benzocaine
Phenazopyridine
Nitrates/nitrites
Skunk musk
Case reports
Methemoglobinemia caused by hydroxycarbamide (hydroxyura) ingestion in a dog – Wray, JSAP 2008 Treated with methylene blue, oxygen, prbc
transfusion, NAC and fluids Methgb resolved within 16hrs
Cyanosis and congenital methemoglobinemia in a puppy – Fine JAAHA 1999 Due to deficiency of methemoglobin reductase
enzyme Causes mild signs Consider preemptive measures before surgical
procedures
Smoke inhalation
Death due to hypoxia from carbon monoxide toxicity
Other complications seen Direct thermal or irritant gas injury- URT, LRT Dermal burn injury ARDS Bacterial pneumonia Neurologic signs
Cyanide toxicity
Incidence and significance remains undefined May contribute in smoke inhalation Found in very low concentrations in foods in the form
of amygladalin Iatrogenic sources (nitroglycerin, nitroprusside)
Several intrinsic biochemical pathway for CN detox exists Formation of thiocynate
Hallmark- histotoxic hypoxia
Cyanohemoglobin further contributes to hypoxia
Carbon monoxide toxicity
Nonirritant gas, colorless, odorless
CO binding to hgb is > 200x the affinity than of O2 to hemoglobin Also shifts O2-hemoglobin curve to the left
Produced by incomplete combustion of hydrocarbons in fire, car exhaust, charcoal grills, generators
Carbon monoxide pathophysiology
Two main mechanisms Hypoxic injury Cellular toxicity
May explain acute and delayed effects
Clinical signs
Initial clinical signs reflects the gas’s effect on the CNS
Cardiopulmonary signs (tachycardia, tachypnea, arrhythmia)
Delayed neurologic signs
Classic cherry red mucous membranes
CO toxicity literature review
Carbon monoxide toxicity: a case series – Berent 2005 JVECC 4 dogs and 2 cats from the same household 5/6 survived (one euthanized for abdominal mass) 4/5 were thought to be temp deaf during recovery Treated with supportive care, o2, oxyglobin
Full recovery following delayed neurologic signs after smoke inhalation in a dog- Mariani JVECC 2003. DNS (delayed neuropsychiatric syndrome)
Mech not completely understood
Newer literature
The association of physical exam abnormalities and carboxyhemoglobin concentrations in 21 dogs trapped in a kennel fire - Ashbaugh JVECC 2012 Recorded clinical parameters, samples were taken on
admission and 24hrs later Clinical parameters associated with high levels of
carboxyhemoglobin RE/abnormal auscultation, lower temp Altered mental status and longer hospital stay
O2 therapy resulted in faster decline in carboxyhemoglobin
Successful outcome in a dog with neurologic and respiratory signs following smoke inhalation- Guillaumin JVECC 2013
Pulse oximetry
Pulse Ox Estimate of Sao2 Based on the measurement of the
ratio of light absorbed by tissue (660nm) to that at an infrared wavelength (940nm)
Absorption ratio reflects arterial oxygen saturation
Does not account for various hemoglobin species (carboxy, methgb) Co-oximetry
Pulse ox gap: difference between the % saturation measured and PaO2
References Full recovery following delayed neurologic signs after smoke inhalation in a dog.
Mariani JVECC 2003.
Clinical and neuropathologic findings of acute carbon monoxide toxicity in Chihuahuas following smoke inhalation. Kent, et al JAAHA 2010.
Methemoglobinemia caused by hydroxycarbamide ingestion in a dog. Wray 2008.
Successful outcome in a dog with neurologic and respiratory signs following smoke inhalation. Guillaurmin, et al JVECC 2013
The association of physical examination abnormalities and carboxyhemoglobin concentrations in 21 dogs trapped in a kennel fire. JVECC 2012.
Carbon monoxide toxicity: a case series. JVECC 2005.
Small animal critical care medicine. Silverstein, Hopper, 1st edition. Chapters 28, 86, 87, 9
Cyanosis and congenital methemoglobinemia in a puppy. Fine, et al JAAHA 1999.
The hemoCue for point of care hemoglobin measurement and packed cell volume estimation in cats. Posner JVECC 2005.
Determination of p50 for feline hemoglobin. Herrmann JVECC 2005.
Guyton Textbook of medical physiology 11th edition. Chapter 39 and 40
Fluid, electrolyte and acid-base disorder in small animal practice 4th edition. DiBartola Pages 287-301.
Textbook of respiratory disease in dogs and cats. King Pages 181- 192.
Respiratory physiology 8th edition. West Ch 3-6.
Respiratory function of hemoblobin. Hsia NEJM 2007.
Hypoexima: A quick reference. Bach Vet Clincs of NA 2008.
The veterinary ICU book. Wingfield, Raffe. Ch 2 and 21.
Questions?