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

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Presentation on theme: "Cyanosis Pathophysiology rounds Gideon Daniel, DVM Internal medicine resident 8/22/13."— Presentation transcript:

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

2 Objectives  O2 transport  Selected disease processes  Shock  Methemoglobinemia  Smoke inhalation  Cyanide  Carbon monoxide

3 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”


5 O2 transport  Ventilation  Pulmonary gas exchange  O2 interaction with hemoglobin (hgb)  O2 delivery to tissue  Extraction of O2 at the tissue

6 Ventilation  Mechanical process that causes gas to flow into and out of the lungs  V T = V A + V D  V T : total ventilation  V A : alveolar ventilation  V D : dead space ventilation  PCO2 (arterial CO2 tension): primary driving force for ventilation  PCO2 = VCO2/ V A x K  VCO2 – total volume of CO2 produced by metabolism

7 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

8 Inspired Gas  Warmed and saturated with water vapor (in trachea)  P H20 : 47mmHg at normal body temp (37 C)  PIO2 (partial pressure of inspired oxygen)  PIO2 = (P B – P H20 ) x FIO2 = (760-47) x 0.21 = 150mmHg

9 Alveolar Gas concentration  Less than inspired air in trachea  Due to addition of CO2 from pulmonary capillary blood  Estimated form alveolar gas equation  P A O2 = PIO2 – PaCo2/ R  R= Respiratory quotient = 0.8  Normal: 150 – (40/0.8) = 100mmHg

10 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


12 Causes of hypoxemia  low PIO2  Hypoventilation  R-to-L Shunts**  Diffusion barrier  VQ mismatch

13 Low PI02  Relatively uncommon  Decrease in barometric pressure (high altitudes)  Improper inhalant anesthetic technique

14 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

15 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)

16 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:  Q s /Q t = (S C02 – Sao 2 ) / (S C02 - Sv O2 )  > 10% abnormal

17 VQ mismatch

18 Clinical approach


20 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  is the solubility of oxygen in plasma  Normal in dogs ~20 mL o2/dL

21 Hemoglobin

22 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 Hg HQ by 3.1

23 Oxygen binding to hemoglobin

24 Oxyhemoglobin dissociation curve 95-99%Normal 90-94%Moderate Hypoxia <90%Severe Hypoxia

25 Factors affecting the curve

26 Summary Shift to the right (tissue) Shift to the left (lungs) EffectsDecreases affinity for O2Increases affinity for O2 P50IncreaseDecrease COIncreaseDecrease H+IncreaseDecrease TempIncreaseDecrease 2,3 DPGIncreaseDecrease Bohr effect: hgb’s oxygen binding affinity is inversely related to acidity and Co2 Haldane effect: deoxygenating blood assists in carrying CO2

27  Carried in 3 forms:  Dissolved  Bicarbonate  CO2 + H 2 0 ⇋ H2Co2 ⇋ H+ ⇋ HCO3-  Carboxyhemoglobin  More linear than O2 dissociation curve  Small differences between arterial and venous CO2 (5mmhg) Carbon dioxide transport


29 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

30 Oxygen extraction ratio (OER)  OER: O2 consumed (VO2)/(DO2)  OER = [(SaO2- SvO2)/SaO2] x 100  Normal ~  Lowered OER represents improved relations of DO2 to VO2

31 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

32 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

33 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%

34 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


36 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

37 Etiologies  Acetominophen  Topical benzocaine  Phenazopyridine  Nitrates/nitrites  Skunk musk

38 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


40 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

41 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

42 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

43 Carbon monoxide pathophysiology  Two main mechanisms  Hypoxic injury  Cellular toxicity  May explain acute and delayed effects

44 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

45 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  DNS (delayed neuropsychiatric syndrome)  Mech not completely understood

46 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

47 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


49 References  Full recovery following delayed neurologic signs after smoke inhalation in a dog. Mariani JVECC  Clinical and neuropathologic findings of acute carbon monoxide toxicity in Chihuahuas following smoke inhalation. Kent, et al JAAHA  Methemoglobinemia caused by hydroxycarbamide ingestion in a dog. Wray  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  Carbon monoxide toxicity: a case series. JVECC  Small animal critical care medicine. Silverstein, Hopper, 1 st edition. Chapters 28, 86, 87, 9  Cyanosis and congenital methemoglobinemia in a puppy. Fine, et al JAAHA  The hemoCue for point of care hemoglobin measurement and packed cell volume estimation in cats. Posner JVECC 2005.

50  Determination of p50 for feline hemoglobin. Herrmann JVECC  Guyton Textbook of medical physiology 11 th edition. Chapter 39 and 40  Fluid, electrolyte and acid-base disorder in small animal practice 4 th edition. DiBartola Pages  Textbook of respiratory disease in dogs and cats. King Pages  Respiratory physiology 8 th edition. West Ch 3-6.  Respiratory function of hemoblobin. Hsia NEJM  Hypoexima: A quick reference. Bach Vet Clincs of NA  The veterinary ICU book. Wingfield, Raffe. Ch 2 and 21.

51 Questions?

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