1. Natural disease and Diving
James Fulcher, M.D.
Shanna Williams, PhD
9/5/2013
8-10:00am

2. Outline Scuba’s effects Sudden cardiac death
Pulmonary disease and complications
Discuss Scuba’s effects in light of pathology presented (this will be completed in each organ system separately)
Remember one thing- these are extreme examples that killed someone that was not breathing compressed air in a potentially deadly environment
Less impressive (subclincal) disease could be fatal while diving

3. Scuba’s Effects on Heart Disease
In a nutshell, diving is exercise
In these cases, diving might have been the most exercise they have had in years.
These patients might have a bad outcome walking around the grocery store, climbing stairs.

4. Immersion effect on the body
Cardiovascular changes during SCUBA diving: an underwater Doppler echocardiographic study
Body immersion induces blood redistribution (from peripheral to intrathoracic vessels) and is a powerful autonomic stimulus (activating both parasympathetic and sympathetic systems). For these reasons, concerns have been raised about the safety of diving for subjects with previous heart disease. The aim of this study was to evaluate cardiovascular changes occurring during recreational SCUBA diving, as assessed by underwater Doppler echocardiography.
Methods
Eighteen healthy experienced divers underwent a 2D Doppler echocardiography basally, during two 15' steps of still SCUBA diving at different depths (10 m followed by 5 m) and shortly after the end of immersion.
Acta Physiol (Oxf). 2013 Sep;209(1):62-8. doi: /apha Epub 2013 May 22.
Cardiovascular changes during SCUBA diving: an underwater Doppler echocardiographic study.
Marabotti C1, Scalzini A, Menicucci D, Passera M, Bedini R, L'Abbate A.

5. Immersion effect on the body
Results
During dive, left ventricular (LV) diastolic volume and early left ventricular filling significantly increased (5 m vs. basal: P < 0.05 andP < 0.01, respectively), while both deceleration time of the early filling rate and late diastolic filling velocity significantly decreased (5 m and 10 m dive vs. basal: P < 0.01). LV volume increase and diastolic filling changes persisted at postdive evaluation, where a significant decrease in heart rate was also observed (P < 0.01 as compared to basal, 5-m and 10-m dive).
Conclusion
This study documents that shallow-depth SCUBA diving induces LV enlargement and diastolic dysfunction. Direct underwater evaluation by Doppler echocardiography could be an appropriate tool for unmasking subjects at risk for underwater-related accidents.

6. Let’s think about what this means
Coronary arteries are filled during diastole
During systole, these arteries are compressed- particularly at the subendocardial level
Coronary artery filling pressure is Aortic diastolic pressure minus Left ventricle end diastolic pressure (LVEDP)
We just learned that diving increases LVEDP

7. Atherosclerosis- Scope of the disease
Per Robbins Pathology,
Atherosclerosic Cardiovascular Disease (ASCVD) causes about half of all deaths in the US and many developed countries
Myocardial infarction is responsible for about ¼ of deaths in the US.
Significant mortality and morbidity associated with CNS associated atherosclerosis

8. ASCVD Risk Factors Framingham heart study- started in 1948
Risk is multiplicative
2 risk factors increase risk 4 times…
Age
4th to 6th decade
Gender
Male gender
Estrogen’s protective effect is variable
Genetics
Some mendelian disorders but most are multifactorial, clustering with hypertension and diabetes

9. Modifiable Risk Factors
Hyperlipidemia
LDL vs HDL, Statins, Omega-3 fatty acids
Hypertension
Smoking
Prolonged use double death rate
Diabetes
Doubles risk
100 fold risk of Atherosclerotic associated gangrene

11. Pathogenesis Response to injury hypothesis Chronic endothelial injury
Accumulation of lipoproteins in vessel wall
Monocyte adhesion, migration to intima, formation of foam cells/macrophages
Platelet adhesion
Factor release
Smooth muscle proliferation
Lipid accumulation

12. Progression
Robbins

13. Progression of Atherosclerosis
Timeline is variable
“Clinically silent” is critical
Ends with enough blockage of the vessel to kill the individual
The degree of blockage depends on the health of the individual

14. Acute Plaque Change Sudden death Rupture/fissuring Erosion
Hemorrhage into atheroma
Plaques do not need to be large to have acute change
Robbins

15. Plaque Rupture- increased during stress or exercise

16. Aortic Dissection Related to plaques and hypertension Exercise
Stimulant drug abuse
Aortic plaques can occur outside of coronary plaques

17. Myocardial Infarction
AKA Heart attack
Epidemiology
Risk factors
Age
10 % of myocardial infarctions occur in patients less than 40 years of age
45% of myocardial infarctions occur in patients less than 65 years of age
Atherosclerosis
Equal frequency in blacks and whites
Men have a greater risk than women
After menopause there is significant development of coronary artery disease

18. Myocardial Infarction Pathogenesis
Progression of ischemic necrosis
The subendocardium is most vulnerable therefore this is the location at which irreversible injury tends to occur initially
Persistence of ischemia results in progression of the ischemia to involve increasingly more of the transmural thickness
Robbins and Cotran Pathologic Basis of Disease

19. Myocardial Infarction Pathogenesis
Factors that affect the morphologic features and size of an infarct include
Location, severity , and rate of development of the obstruction
Size of affected vascular bed
Duration of occlusion
Metabolic demands
Collateral blood supply
Oxygenation of blood
Chronic ischemia can stimulate development of collateral blood vessels and therefore provide some buffering to the time required to cause necrosis

20. Sudden Cardiac Death
Definition: Sudden cardiac death refers to unexplained death of cardiac origins in persons without symptomatic heart disease or occurring soon after symptoms

21. Sudden Cardiac Death Pathogenesis
Generally seen in the setting of ischemic heart disease
Other causes- (10-20%)
Congenital structural defects
Aortic valve stenosis
Mitral valve prolapse
Myocarditis
Cardiomyopathy
Dilated
Hypertrophic
Pulmonary hypertension
Cardiac hypertrophy
Cocaine
Catecholamines
Other

22. Sudden Cardiac Death Morphology
Coronary atherosclerosis with >75% stenosis involving one or more vessels is seen in 80%-90% of patients
Plaque disruption is seen in about 50% of cases
Acute MI is seen in about 25% of case- this is limited by our ability to “see” acute MI at autopsy

23. Sudden Cardiac Death
Electrical abnormalities of the heart that predispose to sudden cardiac death include
Long QT syndrome
Short QT syndrome
Wolff-Parkinson White syndrome
Others
Channelopathies is a term that refers to a group of disorders that is due to mutations in genes needed for normal ion channel function
This include the long QT syndrome
Various mutations can predispose to this
Certain channelopathies can affect other tissues as well such as skeletal muscle

24. Arrhythmogenic Right Ventricular Cardiomyopathy
This is an inherited disorder (most commonly autosomal dominant) of cardiac muscle that results in right ventricular failure and various rhythm disturbances which may result in sudden death.
This process is characterized by fibrofatty replacement of the right ventricle and to much lesser degree the left ventricle
The right ventricular wall is thin
Modified from Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition, 8th ed.
Copyright © 2009 Saunders, An Imprint of Elsevier
The image on the left is a gross photograph of the heart in a patient with arrhythmogenic right ventricular cardiomyopathy. Notice the replacement of the right ventricular free wall with fat. The right image is a histologic section of the right ventricle. Notice the fibrosis (blue) and fat.

25. Hypertrophic Cardiomyopathy
Definition: Hypertrophic cardiomyopathy is characterized by:
Myocardial hypertrophy,
A poorly compliant left ventricular myocardium resulting in abnormal diastolic filling
About 25% of patients have left ventricular outflow tract obstruction at rest caused by contact between anterior leaflet of mitral valve and interventricular septum during systole

26. Hypertrophic Cardiomyopathy Morphology
Gross: Myocardial hypertrophy usually without ventricular dilatation. Classically there is asymmetrical thickening of the ventricular septum as compared with the free wall of the left ventricle.10% of cases have a symmetrical thickening. The thickened septum bulges into the lumen of the left ventricle. There is often endocardial thickening of the left ventricular outflow tract and thickening of the anterior mitral leaflet
Microscopic: Myocyte hypertrophy, Myocyte disarray, and fibrosis.
Modified from Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition, 8th ed.
Copyright © 2009 Saunders, An Imprint of Elsevier
In frame A note the septum bulging into the left ventricular outflow tract. Frame B: Note the disarray and branching of the myocytes. There is also interstitial fibrosis.

27. Hypertrophic Cardiomyopathy Clinical
In symptomatic patients the most common complaint is dyspnea, mostly due to diastolic ventricular dysfunction. Other symptoms include syncope, angina pectoris, and fatigue.
Syncope can occur without warning during exertion and may be due to
Outflow tract obstruction worsening with increased contractility
Ventricular or atrial arrhythmia
Angina due to focal myocardial ischemia
Cardiac hypertrophy
Elevated left ventricular pressure
Abnormal intramural arteries
Unfortunately the first manifestation of this disorder may be sudden cardiac death, frequently in children and young adults during or after physical exertion.

28. Hypertrophic Cardiomyopathy Clinical
There may be a harsh systolic ejection murmur caused by ventricular outflow obstruction due to the anterior mitral leaflet moving toward the ventricular septum during systole.
Other complications include include:
Atrial fibrillation
Ventricular arrhythmias
Embolization due to mural thrombus formation (possible stroke)
Cardiac failure
Sudden death
Hypertrophic cardiomyopathy is the most common cause of sudden, unexplained death in young athletes.

29. Hypertrophic Cardiomyopathy Clinical Manifestations
Mild forms are often asymptomatic S4
Due to blood flow striking a stiffened left ventricle
Findings in those with outflow obstruction
Carotid pulse
Brisk rise in early systole
Quickly declines due to obstruction
Systolic murmur of LV outflow obstruction
Crescendo-decrescendo
Heard best at left lower sternal border
Mitral regurgitation may be heard

30. Hypertrophic Cardiomyopathy Diagnosis
Diagnosis is suspected based on murmur and symptoms
Consider in unexplained syncope in young athletes
EKG
Left ventricular hypertrophy
Left atrial enlargement
Atrial and ventricular arrhythmia
Echocardiography
Asymmetrical wall thickness can be identified
Outflow tract obstruction may be seen
Parasternal long-axis view (during systole) of hypertrophic cardiomyopathy (HCM). Severe LV hypertrophy is present, as is systolic anterior motion of the anterior mitral valve leaflet (arrow).

31. “B” is the problem

32. Polyarteritis Nodosa

33. The next charts are FYI references
Lots of these are testable now in the living and the dead
Costs vary but are generally $500-$2000
There are more genes that cause the phenotypes (disease) than we can test for
AKA- if you have the “right” mutation, we are really good, if not- we will miss it everytime

34. Arrythomogenic Right Ventricular Cardiomyopathy (ARVC)
Structure Affected
Myocyte desmosomes
Gene Association & Inheritance Pattern AD
Plakoglobin (PKP2)
Desmoplakin (DSP)
Plakophilin-2 (PKP2)
Desmoglien (DSG2)
Desmocollin (DSC2) AR
Clinical Presentation
Ventricular arrhythmias
Sudden cardiac death
Gross Anatomical Change
Fibro-fatty myocardial replacement →
RV dilation/myocardial thinning
Histopathology
Fibro-fatty myocardial replacement
Necrotic myocytes
Patchy mononuclear infiltrate
EKG Findings
Epsilon wave
RBBB
T wave inversion (V1-3)

35. Familial Hypertrophic Cardiomyopathy
Structure Affected
Sarcomere proteins
Gene Association & Inheritance Pattern AD
Beta (β)-myosin heavy chain (MYH7)
Myosin binding protein C (MYBPC3)
Cardiac troponin T (TNNT2)
Cardiac Troponin I (TNNI3)
Clinical Presentation
Left ventricular outflow obstruction
Diastolic dysfunction
Myocardial ischemia
Mitral regurgitation
Gross Anatomical Change
Left ventricular hypertrophy
Histopathology
Hypertrophied myocytes
Myocyte architecture disarray
Interstitial fibrosis
Decreased arteriole diameter
EKG Findings
Strain pattern
Pathologic Q waves
Left axis deviation
LVOT & MR have associated systolic murmurs (crescendo-decrescendo after S1 at apex and l sternal border and holosystolic murmur at apex radiating to axilla)
Decreased intramural arteriole diameter->myocyte ischemia->gross myocyte fibrous replacement
Pathologic Q-septal depolarization of hypertrophied tissue
Left axis deviation (LAD) is a condition whereby the mean electricalaxis of ventricular contraction of the heart lies in a frontal plane direction between -30° and -90°. This is reflected by a QRS complex positive in lead I and negative in leads aVF and II.
Strain pattern (downsloping ST &T in lateral leads)

36. Catecholinaminergic Polymorphic Ventricular Tachycardia (CPVT)
Structure Affected
Sarcoplasmic reticulum
Gene Association & Inheritance Pattern AD
Cardiac ryanodine receptor (RyR2) AR
Calsequesterin-2 (CASQ-2)
Clinical Presentation
Stress induced V tach/V fib
Syncope
Juvenile sudden death
Gross Anatomical Change
None identified
Histopathology
EKG Findings
VT with beat to beat variation
Bidirectional VT (QRS alternans)
RyR2-channel that mediates Ca release from the SR, mutation increases leakiness, increasing after depolarization, leading to ventricular arrhythmias
Calsequestrin-2-protein (bound to RyR2) = major SR Ca reservoir

37. Long QT Syndrome Structure Affected Na, K, Ca channels, Ankrin B
Gene Association
LQT1 through LQT12 (1-3 most common)
Inheritance AD
Romano-Ward syndrome AR
Jervell and Lange-Nielsen syndrome
Clinical Presentation
Long QT
Bilateral sensorineural hearing loss
Gross Anatomical Change
Fatty infiltration AV node
Histopathology
EKG Findings
Men QT > 470ms
Women QT > 480ms in F
Includes many (Romano-Ward syndrome and Jervell and Lange-Nielsen syndrome etc.)
These mutations tend to prolong the duration of the ventricular action potential (APD), thus lengthening the QT interval. 
QT measured from lead II

38. Brugada Syndrome (Types B1-B6)
Structure Affected
Myocyte Sodium Channel
Gene Association AD
Sodium Channel 1.5 subunit (SCN5A)
Sodium Channel 1.8 subunit (SCN10A)
Clinical Presentation
V fib
Sustained polymorphic v tach
Syncope
Gross Anatomical Change
Rarely
RV outflow tract obstruction
Localized inflammation and fibrosis
Histopathology
May include
Right ventricular myocarditis
EKG Findings
Pseudo RBBB and persistent ST elevation in V1-V2
Coved ST formation
Saddleback ST formation
Pathogenesis Summary
Gene mutation→delayed Na channel current→
reentrant extrasystole→V tach/V fib→sudden cardiac death

39. Noonan Syndrome Structure Affected
Cell signaling & differentiation apparatus
Gene Association & Inheritance AD
PTPN11
SOS1
RAF1
KRAS
NRAS
BRAF
Clinical Presentation
Characteristic facies
Neck webbing
Short stature (delayed growth)
Pectus excavatum ,carinatum, or scoliosis
Delayed puberty
Cryptorchidism/infertility
Gross Anatomical Change
Pulmonary stenosis
Hypertrophic cardiomyopathy
Histopathology
Patchy fibrosis with myocyte disarray
Myocyte size variability/hypertrophy
Foci chronic inflammation
EKG Findings
Left Axis Deviation
Abnormal Q Waves
Characteristic facies:
Deep philtrum
Widely spaced eyes (blue/blue-green) Low-set ears rotated backward
High-arched palate
Poor tooth alignment
Micrognathia

40. What about the lungs and diving
We are potentially increasing vascular congestion
We are increasing alveolar pressures
Lung overinflation injuries are easy to understand with two facts in mind-
We are breathing air at increased pressure, on ascent volume of air inside alveoli increases
Alveoli are not particularly sturdy

41. Normal lung

42. Relatively normal lung

43. Emphysema in a smokers lung

44. Lots of blood in the trachea
This is a extreme example but a lung lesion that is vascular would not behave well while diving
Particularly central masses with large feeding vessels

45. Asthma and diving
Reactive bronchioles increase air trapping at the level of the alveoli
The most common gross autopsy finding at autopsy is hyperinflation
Microscopic findings are diagnostic

46. Reactive bronciole

47. Aspiration Thank god vomit will flow through a regulator
Chew your food well
Hangovers and diving are generally a bad idea
A quick ascent after some small bronchiole plugging would act like asthma

48. Conclusions Scuba is exercise that can be mild or severe
Immersion increases diastolic filling creating diastolic dysfunction
Lung injuries occur due to overinflation, risk factors include air trapping diseases (asthma)and microscopic tissue loss (emphysema)
There is no enforced “fitness to dive” program/screening for recreational diving
Until there is better screening, there will be cardiac and pulmonary events while diving