Cardiomyopathies, Myocarditis, Pericarditis, Tumors, and Transplant Flashcards
What two general categories of cardiomyopathies are there and how do these differ?
Primary and Secondary
Primary
• Confined to Myocardium - (e.g. myocarditis)
Secondary
• Systemic - (e.g. Hemochromatosis)
What are 3 general types of Cardiomyopathy will you generally see?
Dilated Cardiomyopathy
• ALL CHAMBERS of the heart are HUGE
Hypertrophic Cardiomyopathy
• Ventricular Walls are thickened, possible causing atrial dilation
Restrictive Cardiomyopathy
• Something is causing the heart to be squeezed
Differentiate the typical causes of Dilated, Hypertrophic, and Restrictive Cardiomyopathy.
Dilated
• SYSTOLIC DYSFUNCTION (fucked up contractility)
• ^^Most commonly caused by Chronic Alcoholism
• Dystrophin gene mutations
Hypertrophic
• DIASTOLIC DYSFUNCTION (impaired contractility)
• Idiopathic Hypertrophic Subaortic Stenosis (IHSS)
Restrictive
• Diastolic dysfunction from Infiltration of Material
• common culprits => AMYLOIDOSIS, HEMOCHROMATOSIS, RADIATION INDUCED FIBROSIS
What drug type of myopathy is misfolded dystrophin linked to?
• What drug do we give that can have a similar effect on the heart?
dystrophin - protein mutated in muscular dystrophy (x-linked rec., elarged calves) is part of a complex that links cytoskeleton of muscle fiber to surrounding extracellular matrix
• Doxorubicin - (anthracycline - DNA chelating agent)
Describe the physical appearance of a heart of a person with a Dilated Cardiomyopathy?
• Major risk of these morphologic changes?
- Flabby
- All Chambers Dilated
- Thin Walls - but VARIABLE VENTRICULAR THICKNESS
major risk:
• Mural thrombi and Emboli
• ALSO, see valvular regurgitation due to chamber dilations
What vitamin deficiency commonly seen in alcoholics may commonly lead to Cardiomyopathy?
• TYPE of cardiomyopathy?
• DISEASE MANIFESTATIONS
• Enzyme affected/process affected
BeriBeri caused by a thiamine (vitamin B1) deficiency leads to a DILATED cardiomyopathy i
TWO TYPES:
• wet beriberi - causes heart failure
• dry beriberi- affectsnervous system - leading to psychiatric symptoms
Enzyme:
• Affects Alpha-ketoglutarate dehydrogenase in the CITRIC ACID CYCLE
What are hypertrophic cardiomyopathies often diagnosed?
On autopsy after an athlete drops dead while playing sports (these usually aren’t too symptomatic prior to this)
Hypertrophic Cardiomyopathy
• Part of Heart Cycle affected
• Appearance/cause of death
Diastole is affected in this disease that results from ASYMMETRIC INTERVENTRICULAR HYPERTROPHY this leads to obstruction of Ventricular OUTFLOW also known as Idopathic Hypertrophic Subaortic Stenosis (IHSS)
Hypertrophic Cardiomyopathy
• Who is affected?
• Root etiology?
• what is the actual cause of death?
- 1/500 people are affect, and adults and children are affected equally
- 100% Genetic and many different proteins may be defective but most often it is ß-MYOSIN HEAVY CHAIN that gets affected
- Actual cause of death is Arrhythmia
What parameter of heart function is most affected in patients with hypertrophic cardiomyopathy?
• why are these patients predisposed to Arrhythmia?
• Key Histological Finding
• End Diastolic Volume is reduced because of septal enlargement in the left ventricle ultimately leading to reduced cardiac output
- Excess collagen deposited between myocytes prevents communication
- myocytes should be aligned in parallel however in Hypertrophic Cardiomyopathy they are swirls
What is the function of the ß-myosin heavy chain?
KEY COMPONENT of the SARCOMERE
***Note: most clinical findings related to Hypertrophic Cardiomyopathy are related to DECREASED COMPLIANCE AND FILLING OF LEFT VENTRICLE
Restrictive Cardiomyopathy
• Size Changes
• Gross Findings
• Etiology of Gross Findings
Size is NOT really affected in restrictive cardiomyopathy except for Bi-atrial dilation due to resticted movement of ventricle
• Myocardium will be firm
What type of cardiomyopathy is associated with HFE gene mutation?
• Symptoms Seen in these patients, cause?
• Primary or secondary?
RESTRICTIVE Cardiomyopathy of the LEFT VENTRICLE
HFE gene mutation = Hepcidin protein = HEREDITARY HEMOCHROMATOSIS => no Hepcidin means ferroportin stays upregulated and Iron gets deposited into tissue including the Heart
• patients have Liver Cirrhosis, Pancreatic Problems, Heart Problems, Reproductive Problems, and Skin Color Changes
What phase of the heart cycle is affected by hereditary hemochromatosis?
Diastole due to failure of stiffened ventricle to expand - this is what makes it a RESTRICTIVE Cardiomyopathy
True or False, Iron Overload Cardiomyopathy is the same as hereditary hemochromatosis and they are both considered restrictive cardiomyopathies.
FALSE, iron overload cardiomyopathy (secondary to lots of blood transfusions etc.) is just considered a dilated cardiomyopathy now instead of a restrictive one like Hereditary Hemochromatosis
What Three NON-viral pathogens are commonly associated with Cardiomyopathy?
•what kind of cardiomyopathy is implicated?
3 non-viral pathogens:
•Toxoplasmosis gondii
• Borrelia burgdoferi
• Trypanosoma cruzi
Which should be higher on you differential viral infectious myocardiditis or bacterial infectious myocarditis?
• What will you be looking for on biopsy?
*VIRAL infectious myocarditis is much more common (should be higher on you dd)
• Since the most common cause is viral you will usually see Lymphocytic Infiltrate
What will be the heart’s gross appearance in any type of infective myocarditis?
• microscopic appearance?
Gross:
• May be NORMAL or DIALATED
• May be Flabby and pale
• Mural Thrombi may be present
Microscopic Appearance
• Inflammatory infiltrate(lymphocytes-viral, neutrophils-bacterial)
• edema
• myocyte injury
A South American (who lives in a house with a thatched roof) comes in with an infectious myocarditis. What should pathogen should you suspect?
• diagnosis?
• carrier?
Trypanosoma cruzi - protazoan is probably the pathogen to blame
- *Dx: Chagas Disease
carrier: Reduviid Bug**
**note this diagnosis is typically made on the basis of a history and a peripheral blood smear
What would you expect to see if you biopsied the heart of someone with Chagas disease?
Trypanosomes (little fish egg looking gametes) are bundled up inside myocytes
Surrounding infected myoctes will be inflammatory infiltrate of NEUTROPHILS, LYMPHOCYTES, MACROPHAGES, EOSINOPHILS (occasionally)
What type of infectious myocarditis might be aqcuired by a pregnant lady changing the litter box?
• Other people who might get this?
Toxoplasma gondii - obligate intracellular parasitic PROTOZOAN
•Preganant women and heart transplant patients contract this most often
• NOTE: in transplant patients its most often a reactivation of a latent infection - most ppl. around cats are carriers
What is the histological appearance of Toxoplasma gondii?
pseudocyst containing BRADYZOITES of T. gondii appears IN myocardial cell
Borrelia burgdorferi
• type of pathogen?
• Carrier?
• Disease caused?
• Tale-Tale Sign?
Borrelia burgodorferi - bacteria that causes lyme disease. This is typically carried Ixodes scapularis (black legged tick) and Ixodes pacificus (WESTERN black legged tick)
• sign = Target Rash
What are 3 causes of NON-infectious myocarditis?
• Immune mediated (e.g. SLE)
• Hypersensitivity/Drug Mediate
• Giant Cell Myocarditis
T or F: Drug hypersensitivity reactions commonly lead to non-infectious myocarditis.
FALSE, these reactions very rarely cause CHF or death
Giant Cell Myocarditis
• Microscopic appearance
• relation to Giant Cell Vasculitis
• Px
Microscopically inflammatory infiltrate with multinucleated GIANT CELLS are seen. FOCAL and often EXTENSIVE NECROSIS is seen.
**This is NOT a progressive form of temporal vasculitis
POOR PROGNOSIS
What are two causes of PERICARDIAL (not myocardial) disease?
• what is the common result of both?
Effusions and inflammatory conditions both result in FIBROSIS AND CONTRICTION
What are some primary and secondary causes of Pericarditis?
• Frequency?
Primary pericarditis - UNcommon
• Viral
• concurrent MYOcarditis
Secondary pericarditis
• Uremia - COMMON CAUSE
• Autoimmune Diseases (Rheumatic Fever, and SLE)
• Metastasis
What causes Uremeia and what condition is this associated with?
Uremia - causes 2° PERICARDITIS
• associated with Renal dysfunction - causing fluid, electrolyte, metabolic, and hormonal abnormalities
What is the typical gross appearance of a pericarditis?
• microscopic?
• Fibrinous Rough Ragged Appearance
• Microscopically you see the bubble gum pink amphorous fibrin deposition at the edges of the myocardium
What are 3 ways in which a pericarditis may progress?
- May cause immediate complications like tamponade
- May resolve
- Progression to chronic fibrosing process
Determine what type of process likely lead to the following pericardial effusions:
*Serous
*Serousanguineous
*Chylous
Serous:
*often caused by heart failure
Serousanguineous:
*blunt chest trauma, malignancy, ruptured MI, Aortic dissection
Chylous:
*mediastinal lymphatic obstruction
What is the most common way to end up with heart cancer?
METASTASIS
What are 4 cancer that you will sometimes see metastasis to heart tissue?
1. Pleural Mesothelioma (48%)
2. Melanoma (28%)
3. Lung Adenocarcinoma (21%)
4. Undifferentiated Carcinomas (19%)
5. Lung Squamous Cell Carcinoma (18%)
6. Breast Carcinoma (16%)
What are 4 ways in which Sarcoma of the Skin, Melanoma, Urothelial Carcinoma, or Non-Hodkin’s lymphoma can get from their primary locations to the heat?
- Through Bloodstream
- Direct Extenstion (of mediastinal mass)
- Intercavitary Diffusion through IVC - RENAL CELL CARCINOMA
- Lymphatics
What symptom might you have that lets you know cancer has spread to the heart?
Effusion
What are two PRIMARY tumors of the heart?
1. MYXOMAS
2. RHABDOMYOMAS
Myxomas
- Prevalence
- Most Frequent location
- Complications
most common primary tumor
Located in the LEFT Atrium most freuquently
These tumors are peduculated and thus movable. This gives them the tendency to slide into the mitral or tricuspid valves to obstruct flow and/or destroy leaflets via wrecking ball effect
What tumor type is associated with cells that look like spiders?
Rhabomyoma
Rhabdomyoma
- epidemiology
- cause
- prognosis
Rhabdomyoma = spider cells
- Typically seen in VENTRICLE of CHILDREN and INFANTS
- Caused by mutation in TSC1 or TSC2 TUMOR SUPPRESSOR genes leading to tubular sclerosis and myocyte overgrowth
• most Spontaneously Regress
What are the major risks associated with cardiac transplants?
- Acute Rejection (Mediated by host T-cell response against graft MHC) and allogenic arteriopathy
- Opputunistic infections and post-transplant lymphoproliferative disorders (PTLD) often caused by EBV
****NOTE: kids who have never been exposed to EBV are the most likely to have severe PTLD effects*****
What is on your differential for lymphocytic infiltration of myocardium?
• How does patient Hx make this easy?
Graft Rejection in Heart Transplant and Viral Myocarditis will both present this way - History of transplant makes this easy
What is allograft arteriopathy?
• critical stenosis of INTIMA (note: elastic lamina and media are left in tact)
this is most likely antibody (b-cell) mediated causing phagocyte release of cytotoxic granules leading to fibrosis of intima over time
*****What is shown here and What are some possible causes of the appearance seen here?
• which is most common
Dilated Cardiomyopathy (you can see all 4 chambers enlarged) could be caused by:
- CHRONIC ALCOHOLISM (beriberi thiamine def.)
- DYSTROPHIN mutation
• DOXYRUBICIN
*****Why did they probably autopsy this person?
They probably dropped dead playing sports and cause of death was unknown - hypertrophic cardiomyopathy
• you can see a banana shaped left venticle that is severly hyptrophied
******What do you suspect the microscopic appearance of fibers in this heart are?
Hypertrophic Cardiomyopathy you will see fibers in disarray - no bundles pointing in any particular direction
*****What genetic mutation is likely associated with this this histologic appearance in a grossly enlarged heart?
ß-Myosin Heavy Chain - this Sarcomeric Protein is the one most often mutated in hypertrophic cardiomyopathy
H and E stain of Hypertrophic Cardiomyopathy
******What has caused the gross appearance of the heart seen here? describe key features.
Color changes can be seen in the myocardium that are too diffuse to be a myocardial infarction (which would tend to affect only areas of the LAD, RA, LCA)
Also Atrial Dilitation can be see due to stiff ventricular tissue that it must push against
CAUSE: CONSTRICTIVE MYOCARDITIS - caused by amyloidosis, hemochromatosis, etc.
******This patient probably experiences the most trouble during which phase of the cardiac cycle?
why?
• KEY HISTOLOGIC FEATURES
- This myocardium has stained positive for PRUSSIAN BLUE STAIN indicating that have hemochromatosis
- This is either a Dilated or REstrictive Cardiomyopathy (depending on if the condition is hereditary)
- in either case DIASTOLE is probably the biggest issue here because the ventricle will likely be STIFF
*****This person has a cardiomyopathy. What was it caused by?
Amyoloidosis = Restrictive cardiomyopathy
**Notice extensive deposition of material BETWEEN heart fibers
*****What’s the differential on this heart tissue? why?
• Lymphocytic infiltrate of the myocardium is indicative of either Viral Myocarditis OR Transplant rejection - use history to tell difference
******What type of myocarditis caused this?
VIRAL - see lymphocytic infiltrate
******What is the etiology here?
NOTHING - this is NORMAL myocardium
******Que es?
Lymphocytic infiltrate of myocardium
*******What is happening here? gross appearance of the heart?
BACTERIAL endocarditis - notice ABCESS formation
• GROSSLY as with viral myocarditis you will see a Flabby, Pale - possible dilated, heart that may have mural thrombi on it
******This person just came from south america and now has myocarditis. Dx?
CHAGAS DISEASE caused by TRYPANOSOMA CRUZI is seen here
• Carried by the Reduviid but
******Type of myocarditis?
Trypanosoma cruzi
******What might immunocompromised people want to avoid to not get this bug?
• Causative agent?
AVOID cats they carry Toxoplasma gondii (pregnant women will want to steer clear too)
*******What caused the skin appearane seen here?
This is Lyme Disease (target rash) caused by BORRELIA BURGDORFERI - carried by Ioxdes Scapularis tick
******What is this?
Giant Cell Myocarditis
******What is the most likely cause of the heart appearance seen here?
- Lab values?
- what microscopic appearance would you expect to see?
UREMIA - secondary but most likely cause of fibrinous pericarditis - caused by DETERIORATION of RENAL FUNCTION
• This person would likely have a very high serum Creatinine
Mircroscopic = Fibrinoid border of myocardium shown here
*****What is seen here?
• Acute Bacterial Pericarditis - FIbrinopurulent (supprative)
******What probably killed this person?
• CHRONIC pericarditis that is CONSTRICTIVE
******Most likely cause?
• SEROUS pericardial effusion most likely due to CONGESTIVE HEART FAILURE or HYPOALBUMINEMIA
********Most likely cause?
Blunt Chest Trauma, Maligancy, Ruptured MI, or Aortic Dissection
*******Most Likely cause?
Mediastinal Lymphatic obstruction causing a Chylous Pericardial Effusion
******What is about to kill this person?
Cardiac Tamonade
******What drug could you possibly treat this patient with?
Vemurafenib (if V600E positive) - because this is metastatic Melanoma of the Heart
******What are some key histological features of this PRIMARY cardiac cancer?
• where is is likely located?
• Gross appearance
MYXOMA - you see a lot of ACELLULARITY with some fibroblast-like Myxoma cells and small vessles
Typically located in the LEFT VENTRICLE - may have a wrecking ball effect on the mitral leaflets
*****Key Histological Features?
• Genetic mutation responsible
• Gross appearance, px?
Key feature - SPIDER CELL in lower middle caused by TSC1 or TSC2 mutation causing a RHABDOMYOMA
Gross appearance is as seen here - huge myoctye overgrowth - the children and infants who get these tumors are lucky because they often spontaneously regress
*******What kind of Transplant rejection is seen here?
ACUTE - notice lymphocytic infiltrate
*****What kind of transplant rejection is seen here?
Allograft Ateriopathy - causing CRITICAL STENOSIS of lumen by expanstino of ONLY THE INTIMA
