Cyanosis Pathophysiology rounds Gideon Daniel, DVM Internal medicine resident 8/22/13.

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?