Chapter 7: Vascular Pathology

Vasculitis

1. What is vasculitis? What's it's prognosis?

• It is inflammation of blood vessel wall - can be both artery or vein (we'll talk about artery in this chapter).
• Initially, the inflammation weakens the blood vessel and can cause aneurysm. Later on, it causes fibrosis
of vessel wall and reduces lumen size and can cause ischemia.
2. What are layers of blood vessel?
• Intima - endothelial sitting on basement membrane
• Media - smooth muscle
• Adventitia - connective tissue

3. What is etiology of vasculitis? Is it infectious?

• Etiology mostly unknown. Not infectious.

4. What are clinical features of vasculitis?

• Non-specific symptoms (only tells us that inflammation is occuring)- fever, fatigue, weight loss, myalgia
• Symptoms of organ ischemia due to -
○ Thrombus formation - damage of endothelium exposes tissue factor and collagen that stimulates
clot formation
○ Reduced lumen size - Injury and healing of vessel wall causes fibrosis that reduces lumen size of the
vessel
○ Aneurysm - inflammation and necrosis of vessel wall weakens it leading to aneurysm

4.5. What are the types of arteritis?

• Large vessel arteritis - affects aorta and its major branches
• Medium vessel arteritis - affects muscular arteries that supplies organs (ex - renal artery, coronary
arteries)
• Small vessel arteritis- affects arterioles, capillaries and venules

Large vessel vasculitis Medium vessel vasculitis Small vessel vasculitis

Temporal Arteritis Polyarteritis nodosa Wegner granulomatosis
Takayasu Arteritis (aka pulseless disease) Kawasaki disease Microscopic polyangiitis
Buerger disease Churg-Strauss
Henoch-Schonlein

Large vessel vasculitis

5. What are clinical features of temporal (giant cell) arteritis - a type of large vessel arteritis?
• Vasculitis of old people (avg age 72) - usually affect female
• Classic location is branches of carotid artery-
○ Temporal artery - old people with new onset headache (classic involvement)
○ Opthalmic artery - see visual disturbance
○ Arteries of jaw - jaw claudication
• Polymyalgia (joint and muscle pain) with flu like symptoms a common association
• ESR is elevated (>100) and CRP too

6. How do you diagnose temporal arteritis? What's a caution point?

• Do a vessel biopsy - see inflamed vessel wall with giant cells and intimal fibrosis
• Granulomatous vasculitis

Vascutis, HTN Page 1.1

 • Granulomatous vasculitis
• Vessel is affected segmentally. Therefore, take a long segment out for biopsy. Negative biopsy doesn't
rule out disease.

Fig - temporal arteritis biopsy. M is the media, I is the intima, F is the area of fibrosis between media and
intima that has narrowed the lumen, circle above M shows giant multinucleated cells, circle left of F
shows inflammation.

7. What is treatment of temporal arteritis (HY)?

• Corticosteroid. Treat soon because of high risk of blindness due to involvement of ophthalmic artery.

8. Contrast symptoms of temporal arteritis with Takayasu arteritis (aka pulseless disease) - a type of large
vessel arteritis?
• Takayasu arteritis is same as temporal arteritis with a couple of exceptions-
○ Affects mainly adults <50. Classic pt is young asian female
○ Affects aortic arch at branch point instead of branches of carotid artery
▪ Visual and neurologic symptoms
▪ Weak or absent pulse in upper extremity (therefore disease called pulseless disease)
▪ ESR is elevated, vasculitis is granulomatous
▪ Treat with corticosteroids

Medium vessel arteritis

9. What is polyarteritis nodosa (a type of medium vessel arteritis)?
• Necrotizing vasculitis that affects vessels in many organs but spares the lungs

10. What is clinical presentation of polyarteritis nodosa? What chemical is it associated with?
• Classic pt is young adults
• Symptoms depend on vessel involved-
○ Renal artery involvement cause hypertension
○ Mesenteric arteries - abdominal pain with melena
○ CNS arteries - neurologic disturbances
○ ESkin lesions
• Associated with serum HBsAG (hepatitis B surface antigen)

11. Correlate pathophysiology of polyarteritis nodosa with imaging.

Vascutis, HTN Page 1.2

11. Correlate pathophysiology of polyarteritis nodosa with imaging.
• The disease has lesion of varying stage in same artery. Early character of disease is that it creates
fibrinoid necrosis that makes the vessel lumen wide (as dead vessel is weak, aneurysms occur). Late
character of disease is that it creates thick fibrosis that narrows the lumen. Therefore imaging gives a
"string-of-pearl" appearance with alternate thick and thin sections.

Fig - the red marking showing fibrinoid necrosis seen in polyarteritis nodosa.

Fig - 'pearl on string' appearance of polyarteritis nodosa

12. What is treatment of polyarteritis nodosa?

• Corticosteroids and cyclophosphamide
• Fatal if not treated

13. What are clinical presentation of Kawasaki disease- a type of medium vessel vasculitis?
• Classic pt is asian child under 4
• Presentation (very nonspecific - pt has like viral infection)
○ Fever>5 days
○ Shrieking irritability - extremely irritable kid
○ Conjuctivitis sparring area right next to iris
○ Erythematous rash of palms and soles and any mucocutaenous membrane (ex - strawberry tongue)
○ Enlarged cervical lymph nodes

14. What artery is preferentially involved in Kawasaki disease? (HY)

• Coronary artery

Vascutis, HTN Page 1.3

 • Coronary artery
• Complication -
○ thrombosis with MI (3 year old kid with MI) - due to endothelial damage and exposure of collagen
and tissue factor
○ aneurysm with rupture
((imagine a kid driving kawasaki bike with his hands and legs, his HR goes up - so the disease affects heart
mainly)

13. What is treatment of Kawasaki disease?

• Asprin to prevent thrombosis (antiplatelet drug - prevents formation of thromboxane A2)
• IVIG (intravenous immunoglobulins)
• Disease is self-limited

14. Why don't you give asprin to kids with viral disease?
• Because they can get Rye syndrome - encephalopathy and massive liver necrosis.

15. What is Buerger disease (medium vessel vasculitis)? How do you treat it?
• It's necrotizing vasculitis involving digits. Presents with ulceration, gangrene, and autoamputation of
fingers and toes.
• Disease associated with Raynaud phenomenon - pale to blue to red color change in digits due to
exposure to cold. Pale and blue color are due to vasospasm; red is due to return of circulation.
• Disease is associated with smoking - treatment is smoking cessation (HY)

Small vessel vasculitis (wegner granulomatosis, microscopic polyangitis, chug-strauss, and Henoch Schonlein)
• The first 3 of these disease can lead to RPGN.
• Henoch Schonlein has IgA deposition and can lead to IgA nephropathy

Wegner Granulomatosis Microscopic polyangiitis

Necrotizing vasculitis Necrotizing vasculitis
Necrotizing granuloma present Granulomas absent
C-ANCA positive P-ANCA positive
Affects nasopharynx, lungs, and kidney Affects lungs and kidney and other organs
Treatment - cyclophosphamide, corticosteroids. Treatment - cyclophosphamide, corticosteroid.
Relapse common Relapse common

Churg-Strauss Henoch-Schonlein purpura

Necrotizing vasculitis Most common vasculitis in children
Necrotizing Granulomas present Palpable purpura in buttocks pathognomic
P-ANCA positive Vasculitis due to IgA immune deposition. Can lead to
IgA nephropathy
See asthma and eosinophila - pt Disease usually follows upper respiratory tract
misdiagnosed with allergies often infection
Affects multiple organs including lung and GI involvement can cause GI pain bleeding
heart
Treat by steroids if necessary. Disease self limited.

16. What is Wegner Granulomatosis (a type of small vessel vasculitis)?

• Necrotizing granulomatous vasculitis involving nasopharynx, lungs, and kidneys. (think weCner's disease-

Vascutis, HTN Page 1.4

 • Necrotizing granulomatous vasculitis involving nasopharynx, lungs, and kidneys. (think weCner's disease-
and imagine a 'C' in a human body passing through nasopharynx, lungs and kidneys).

17. What is presentation of Wegner Granulomatosis?

• Usually affect middle-aged males
• Sinusitis or nasopharyngeal ulceration
• Hemoptysis with bilateral nodular lung infiltrates
• Hematuria due to RPGN (HY)
• Serum C-ANCA level correlate with disease activity

18. How do you diagnose Wegner Granulomatosis? How do you treat it?
• Pt are C-ANCA (cytoplasmic - anti neutrophil cytoplasmic antibodies) positive.
• Biopsy shows large necrotizing granuloma with adjacent necrotizing vasculitis.
• Treatment is Cyclophosphamide and corticosteroids. Relapse is common.

Fig - large necrotizing granuloma seen in Wegner granulomatosis. Granulomas are absent in microscopic
polyangiitis.

19. What is microscopic polyangiitis (type of small vessel vasculitis)? Contrast this disease with Wegner
granulomatosis (WG).
• Necrotizing vasculitis involving multiple organs (hence the name polyangiitis), especially lung and kidney
(similar to WG).
• It's very similar to WG but nasopharyngeal involvement and granulomas are absent.
• Serum P-ANCA (perinuclear - anti neutrophil cytoplasmic antibodis) correlate with disease activity instead
of C-ANCA.
• Treatment is same as WG - corticosteroids and cyclophosphamide. Relapses are common.

20. What are C-ANCA and P-ANCA?

• In C-ANCA, anticytoplasmic antibodies mainly target cytoplasm away from nucleus. In P-ANCA,
anticytoplasmic antibodies mainly target cytoplasm in perinuclear area (hence the name - perinuclear).

21. What is Churg-Strauss syndrome ( a type of small vessel vasculitis)?

• Necrotizing granulomatous vasculitis with eosinophils.
• Involves multiple organs, especially lungs and heart.
• Asthma and peripheral eosinophila.
• P-ANCA correlate with disease activity.

Vascutis, HTN Page 1.5

22. Differentiate Churg-Strauss and microscopic polyangiitis.
Churg-Strauss Microscopic Polyangiitis
• Necrotizing granulomas with eosinophils present • No granulomas
• Peripheral eosinophila and asthma present • No eosinophila or asthma
• Involves heart and lung • Involve lung and kidney
• P-ANCA correlate with disease activity • P-ANCA correlate with disease activity

23. What is Henoch-Schonlein purpura (type of small vessel vasculitis)?

• Vasculitis due to IgA immune complex deposition
• Most common vasculitis in children

24 What is presentation of Henoch-Schonlein purpura?

• Classic presentation is palpable purpura on buttocks and legs. Usually, purpura aren't palpable. It's
palpable in this case due to vasculitis
• GI involvement - GI pain and bleeding
• IgA nephropathy leads to hematuria (HY)
• Usually occurs following an upper respiratory tract infection - the infection generates IgA as IgA protects
mucosal site. Too much IgA cause deposition and disease.

25. How do you treat Henoch-Schonlein purpura?

• Disease is self-limited. Treat with steroids if severe. Disease may recur.

Vascutis, HTN Page 1.6

Hypertension

1. What are two types of hypertension?

• Pulmonary htn
• systemic HTN (systolic or diastolic BP >140/90) - 25% of US popn are hypertensive

2. What are primary and secondary hypertension?

• Primary HTN is when we don't know the etiology. It represents 95% cases of HTN.

3. What are risk factors for primary HTN?

• Age
• Race - high risk for African Americans, low risk for asians
• Obesity
• Stress
• High salt diet
• Lack of physical activity

4. How does high sodium cause HTN?

• Systolic BP is a function of stroke volume
• Diastolic BP is a function of total peripheral resistance
• Sodium increases blood volume and peripheral resistance so increases both systolic and diastolic
BP.

5. Describe renal artery stenosis as cause of secondary HTN. (HY)

• Low blood flow to justaglomerular apparatus causes release of renin. Renin converts
angiotensinogen to angiotensin I. Angiotensin I is converted to angiotensin II by ACE in lung
endothelium. Angiotension II increases BP by two ways -
○ Powerful vasoconstrictor - increases diastolic BP
○ Stimulate adrenal medulla to secrete aldosterone - it increases sodium reabsorption and
potassium excretion from DCT. Water follows sodium and body will have more water -
increases systolic BP.

6. What is clinical presentation of renal artery stenosis (RAS)?

• Atrophy of the stenosed kidney
• Increased blood renin

7. What are important causes of RAS?

• Artherosclerois (classically seen in old males)
• Fibromuscular dysplasia (classically seen in young females) - developmental defect of blood vessel
wall that results in irregular thickening of large and medium sized arteries, specially the renal
arteries.

8. Distinguish benign and malignant HTN.

Benign Malignant
Mild or moderate increase in BP Severe increase in BP (200/120 mm Hg)
Clinically silent May arise from preexisting benign HTN or de novo
Vessels and organs are damaged Pt presents with acute end organ damage - acute renal failure,
over time headache, papilledema
MEDICAL EMERGENCY - pt can have fibrinoid necrosis of blood

Vascutis, HTN Page 2.1

MEDICAL EMERGENCY - pt can have fibrinoid necrosis of blood
vessel wall

Vascutis, HTN Page 2.2

Arteriosclerosis

1. What is arteriosclerosis? What are it's 3 patterns?

- Arteriosclerosis is hardening of arterial wall.
- Patterns-
○ Atherosclerosis - thickening of intima due to plaque(occurs in medium and large sized
vessels)
○ Arteriolosclerosis - thickening of small vessels. Wall thickens due to protein deposition
(hyaline arteriolosclerosis) or hyperplasia of smooth muscle (hyperplastic arteriolosclerosis)
○ Monckeberg medial sclerosis - calcification of media. Not very clinically significant

Artherosclerosis
2. Describe histology of artherosclerosis.
- Artherosclerosis is an intimal plaque that obstructs blood flow. It contains necrotic lipid core with
a fibromuscular wall. The lipid core can undergo dystropic calcification.

Fig - artherosclerosis. M is the media, I is the intima, the circle represents the necrotic lipid core
with cholesterol crystals. The necrotic core is surrounded by a fibromuscular wall.

3. What are 4 most common sites for artherosclerosis?

- Note artherosclerosis occurs in large and medium sized vessels -
Abdominal aorta

Vascutis, HTN Page 3.1

 ○ Abdominal aorta
○ Coronary arteries
○ Popliteal artery
○ Internal carotid artery

4. What are key risk factors for artherosclerosis? (HY)

Modifiable Non-modifiable
HTN Age
Hypercholesteremia (LDL Gender (male and postmenopausal females at high risk.
increases risk and HDL reduces) Estrogen has protective effect on pre-menopausal females)
Smoking Genetics (positive family history)
Diabetes

5. What is pathogenesis of artherosclerosis?

- Intima is damaged --> lipids gets between intima and media -->lipid is oxidized and then
phagocytozed by macrophage --> this makes fatty streak. Fatty streak is seen as early as
teenagers.
- Inflammation, healing and increased deposition of lipid occurs. A fibromuscular cap occurs due to
inflammation and healing.

6. What are some complication of artherosclerosis?

- It's complications account for >50% of disease in western world
- Artherosclerosis is asymptomatic until occlusion is >70% (HY)
a) Stenosis of medium sized vessels (vessels that feed organs)
○ Peripheral vascular disease (popliteal A)
○ Angina (coronary A)
○ Ischemia bowel disease (mesenteric A)
b) Plaque rupture with thrombosis
○ MI (coronary A)
○ Stroke (MCA)
c) Plaque rupture with embolization
○ Results in artherosclerotic emboli (hallmark is cholesterol cleft in emboli)

Fig - presence of cholesterol cleft in embolus is hallmark of artherosclerotic embolus.

d) Aneurysm due to weak wall - MOA - usually media and adventitia receives nutrient by diffusion
from lumen. As artherosclerotic plaque increases, it creates diffusion barrier resulting in atrophy

Vascutis, HTN Page 3.2

 from lumen. As artherosclerotic plaque increases, it creates diffusion barrier resulting in atrophy
of media and adventitia.

Arteriolosclerosis
7. What is arteriolosclerosis?
- Narrowing of small arterioles.
- Causes - deposition of hyaline or hyperplastic media.

8. What is hyaline arteriolosclerosis?

- Proteins leaking into vessel wall causes vascular thickening
- Seen as pink hyaline on microscopy

Fig - pink hyaline in vessel wall characterstic of hyaline arteriolosclerosis

9. What are 2 causes of hyaline arteriolosclerosis? (VHY)

- Benign HTN - high pressure forces protein into the vessel wall
- Diabetes - non-enzymatic glycosilation of basement membrane makes vessel wall leaky and
protein leaks in. This is how diabetes can cause nephrotic syndrome (diabetic nephropathy).

10. What is key consequence of hyaline arteriolosclerosis? (HY)

- Reduced vessel diameter leads to end organ ischemia
- Classically produces glomerular scarring (arteriolonephrosclerosis) which progress to chronic renal
failure (that's how diabetic pt with long standing HTN die

Vascutis, HTN Page 3.3

 Fig - glomerular scarring seen in arteriolonephrosclerosis

11. What is hyperplastic arteriolosclerosis?

- Vessel wall thickens due to hyperplasia of smooth muscle
- 'Onion-skin' like appearance

Fig - onion skin like appearance of blood vessel in hyperplastic arteriolosclerosis

12. What causes hyperplastic arteriosloclerosis?

- Malignant HTN - this leads to acute renal failure (ARF) and fibrinoid necrosis of vessel

13. What are consequences of hyperplastic arteriosclerosis?

- Reduced vessel diameter leads to end organ ischemia
- Malignant HTN may lead to fibrinoid necrosis of vessel wall (another cause of fibrinoid necrosis is
vasculitis)
- Classically causes ARF with 'flea-bitten' appearance - flea-bitten necrosis is due to pin point
hemorrhages (HY)

Vascutis, HTN Page 3.4

 Fig - flea bitten kidney classic of hyperplastic arteriolosclerosis due to pin point hemorrhage -
leads to ARF. Contrast glomerular scarring in chronic renal failure due to arterionephrosclerosis

Monckeberg medial calcific sclerosis

14. Describe Monckeberg medial sclerosis.
- Calcification of media
- Does not obstruct lumen, therefore not clinically significant
- Seen as incidental finding in X-ray or mammography

Fig- Enclosure shows monckeberg medial sclerosis. Note how it's limited to media and doesn't
have much effect on lumen diameter.

Vascutis, HTN Page 3.5

Fig - mammography showing Monckelberg medial calcification of blood vessel

Vascutis, HTN Page 3.6

Aortic Dissection and Aneurysm

1. What is aortic dissection?

- Blood leaks into the media through a break in intima and it rips the media in half

Fig - aortic dissection

2. What are two things required for aortic dissection?

a. A ton of stress - therefore it mainly happens in proximal 10 cm of aorta
b. Pre-existing weakness of media - caused by HTN or inherited defect of connective tissue

3. How does HTN weaken media and lead to aortic dissection?

- HTN leads to hyaline arteriolosclerosis of vaso vasorum (blood vessel that supplies media and
adventitia of aorta). Media weakens due to low supply of blood.

4. What is the most common cause of aortic dissection?

- HTN

5. What are some connective tissue disorders that can lead to dissection?
- Marfan syndrome - mutation in fibrillin-1 protein. Fibrillin is the base on which elastic fibers are
laid down. Media has lots of elastic fibers
- Ehlers-Danlos syndrome - mutation in collagen or proteins that interact with collagen.

6. What is clinical picture of aortic dissection?

- Presents with tearing chest pain that radiates to the back
- Most common cause of death is cardiac tamponade. Other causes include aorta bursting open and
obstruction of arteries that branch off aorta.

Aneurysms
7. What are two classic location of aneurysm?
- Thoracic aneurysm
- Abdominal aneurysm

8. What is a classic cause of thoracic aneurysm?

- Tertiary syphilis- syphilis is end arteritis disease. It affects vaso vasorum and poor blood supply
weakens aortic wall. Weak vessel wall leads to aneurysm
- Tree bark appearance of aorta is classic finding - as vaso vasorum is affected, poor blood supply
leads to fibrosis and scarring

Vascutis, HTN Page 4.1

 Fig - normal aorta (left); tree bark like aorta in tertiary syphilis (right)

9. What are complications of thoracic aneurysm?

- Aortic insufficiency (HY) - as aorta dilates, the valves are pulled apart and can't close well
- Compression of mediastinal structures
- Thrombosis in wall of aneurysm due to disruption in laminar blood flow. It can embolize.

10. What is the most common site of abdominal aortic aneurysm (AAA)? Why is this the most
common site?
- Below the renal arteries and above aortic bifurcation
- Vasa vasorum stops at the level of renal artery bifurcation. Therefore, artherosclerosis of aorta
below this level leads to high level of media atrophy due to poor diffusion of nutrient and gases.
The weak aortic wall leads to aneurysm. (note - most common location of artherosclerosis in
human is abdominal aorta).

Fig: normal abdominal aorta (left); AAA (right) - note calcification of vessel wall and thrombosis
11. What is presentation of AAA?
- >60 year old smoker male with HTN
- Pulsatile abdominal mass that grows with time

12. What is complication of AAA?

- Rupture, especially when >5cm in diameter
- Presents with triad of hypotension, pulsatile abdominal mass and flank pain.

Vascutis, HTN Page 4.2

Chapter 8: Cardiac Pathology
8.1 Ischemic Heart Disease

- Infarction - tissue necrosis due to lack of oxygen

- Ischemia - inadequate blood supply to an organ
- Hypoxemia - (PaO2 < 60mm Hg)
- Early MI - <55 year for men and <45 for women
- 3 most common cause of chest pain in outpatient setting: GERD, anxiety, costochondral tenderness
- Pain with MI is usually described as pressure - elephant sitting on lung. Pleuritic chest pain is more sharp
- ST depression in AVR lead is more specific for pericarditis

1. What is most common cause of ischemic heart disease?

- Artherosclerosis of coronary arteries
- Risk factors same as risk factor for artherosclerosis - age, sex, race, smoking, HTN, diabetes

2. How long does a ischemia last before irreversible injury to cardiac myocytes occur?
- 20 minutes
Angina (reversible injury to cardiac myocytes)
3. Describe Stable angina. What type of damage is suffered by the cells?
- Chest pain develops with physical or emotional stress
- Caused due to >70% stenosis of coronary arteries
- Myocytes undergo reversible injury during stable angina (HY)

4. What is presentation of stable angina? What is seen on EKG?

- Chest pain <20 mins that radiates to left arm or jaw. If > 20 minutes, it causes myocardial infarction
(irreversible damage to myocytes)
- Diaphoresis, SOB
- Pain relieved by rest or nitroglycerin
- EKG shows ST segment depression - because subendocardial ischemia is seen as ST depression. Stable
angina causes subendocardial ischemia because blood vessels travel in epicardium and endocardium is last
part to receive blood.

5. Describe unstable angina.

- Chest pain occurs at rest (that's why called unstable)
- It's due to rupture of artherosclerotic plaque with thrombosis and incomplete occlusion of coronary artery
(rupture usually occurs at neck of plaque)
- Myocytes undergo reversible injury

6. What is presentation of unstable angina? What is seen on EKG?

- Relieved by nitroglycerin (venodialation reduces the work heart has to do)
- High risk of progression to MI because the thrombus can grow.
- ST depression on EKG - same reason as stable angina

Cardiac Page .1

 Fig - unstable angina in coronary artery. Note the dark thrombus. The thrombus has high chance of
growing and leading to MI.

7. What is prinzmetal angina?

- Vasospasm that completely clamps coronary artery - leads to transmural ischemia
- Chest pain irrespective of physical/emotional exertion
- Myocytes undergo reversible injury

8. What is presentation of prinzmetal angina?

- ST segment elevation - as coronary artery completely clamps down, we get transmural ischemia.
Transmural ischemia presents at ST elevation.
- Relieved by NG or calcium channel blockers

Myocardial infarction (irreversible injury to cardiac myocytes)

9. What is MI? What are it's causes?
- Necrosis of cardiac myocytes (irreversible injury)
- Main cause - rupture of artherosclerotic plaque with thrombosis and complete occlusion of coronary
artery
- Other causes - coronary artery vasospasm, emboli, vasculitis (ex - kawasaki disease)

10. What are clinical features of MI?

- Severe crushing chest pain (>20 minutes - cells die after this time)
- Diaphoresis, SOB
- Symptoms not relieved by nitroglycerin
- Mostly involve left ventricle. Right atria and ventricles are usually spared

11. What are key arteries involved in MI?

- LAD (most common) - leads to infraction of anterior wall of LV and anterior interventriclular septum
- Right coronary artery (2nd common) - infraction of posterior wall of LV and posterior interventricular
septum
- Left circumflex artery - infraction of lateral wall of LV

12. Describe initial phase of MI.

- Subendocardial necrosis involving <50% of myocardial thickness
- ST depression (recall subendocardial infraction leads to ST depression and transmrural infraction leads to
ST elevation)

13. What are lab enzyme tests of MI?

- Hallmark of irreversible damage to cell is membrane leak. So, cardiac enzymes will leak.

Cardiac Page .2

 - Hallmark of irreversible damage to cell is membrane leak. So, cardiac enzymes will leak.
- Troponin I - most sensitive and specific marker
○ Rises 2-4hrs post infraction
○ Peaks at 24 hrs
○ Returns to normal 7-10 days
- CK-MB - useful for detecting reinfarction
○ Rises 4-6 hrs after infraction
○ Peaks at 24 hrs
○ Returns to normal by 72 hours

14. What is treatment of MI?

- MONA (morphine, oxygen, nitrates, asprin)
- ACEi (decreases blood volume due to low aldo, and reduces peripheral vasoconstriction (afterload))
- Beta blocker (slow heart rate and reduce risk of arrhythmia)
- Definitive treatment:
○ Fibrinolysis or angioplasty
 Complications: contraction band necrosis and repurfusion injury (reperfusion injury occurs due
to free radical damage by neutorphils and oxygen.

Fig - the box shows necrotic myocytes (no nuclei) and the circles show contraction band necrosis

15. Describe time frame of MI (HY)

Time Microscopic Gross change Complication
change
<4 hrs none none - Cardiogenic shock
- CHF
- Arrhythmia
4-24 hrs Coagulative Dark discoloration - Arrhythmia (it doesn't happen post 24 hrs
necrosis because the conduction system is already
damaged and necrosis occurs < 1 day. So if
arrhythmia don't happen by then, it won't
happen.

1-3 days Inflammatio Yellow pallor - Fibrinous pericarditis (chest pain with friction

Cardiac Page .3

 1-3 days Inflammatio Yellow pallor - Fibrinous pericarditis (chest pain with friction
n rub)- only occurs with transmural infraction
(Neutrophil)

3 day - 1 Macrophage Yellow pallor - Rupture of ventricular free wall (cardiac

week s tamponade), papillary muscle (mitral regurg) or
interventricular septum (shock)
1-3 Granulation Red border (blood vessels)
weeks tissue with emerging from edge of infract
fibroblasts,
collagen and
blood
vessels

Months Fibrosis White scar - Aneurysm

- Mural thrombosis
- Dressler syndrome (autoimmune pericarditis)
(HY)

• Arrhythmia doesn't happen post 24 hrs because the conduction system is already damaged and necrosis
occurs < 1 day.
• Fibrinous pericarditis only occur with transmural infaract
• Papillary muscles are fed by right coronary artery
• Dressler syndrome - inflammation of pericardium and exposure of pericardial antigen can cause
autoimmune attack to pericardium

<1 day 1 day - 1 week 1 week- 1 month >1 month

Coagulative necrosis First neutrophils and then Granulation tissue Scar tissue
macrophage
• Dark discoloration of • Yellow pallor • Red border surrounding yellow • White
heart pallor scar

Cardiac Page .4

Fig - coagulative necrosis of heart showing dark discoloration (<1 day)

Fig- yellow pallor of heart post MI (1 day - 1 week)

Fig - fibrinous pericarditis (fibrin exudate during neutrophil rich stage (day 1-3 post MI) rubs when hear
contracts producing and characteristic friction rub). Only see during transmural infraction

Cardiac Page .5

Fig - 1-3 weeks post MI. The yellow pallor is central area of necrosis (granulation tissue?) surrounded by
emerging blood vessels from edge of infaract

Fig - Months after MI (white scar tissue)

Cardiac Page .6

 Fig - layers of heart muscle

16. What is sudden cardiac death? What is it's etiology

- Unexpected death due to cardiac disease with no symptom or death <1 hr after symptom arise
- Cause : ventricular arrhythmia
- Etiology:
○ Severe artherosclerosis (90% of cases)
○ Less common: cardiomyopathy, mitral valve prolapse, cocaine abuse

17. What is chronic ischemic heart disease?

- Poor myocardial function due to chronic ischemic damage (with or without infraction)
- Can progress to congestive heart failure

Cardiac Page .7

8.2 Congestive Heart Failure (CHF)

1. What is division of CHF?

- Left sided failure
- Right sided failure

2. Differentiate right and left sided CHF.

Left sided failure Right sided failure
Causes - HTN - Most common cause is left
- Dilated cardiomyopathy sided failure
- MI - Left-to-right shunt
- Restrictive cardiomyopathy - Chronic lung disease (cor
pulmonale)
Presentat - Presentation based on pulmonary congestion and - Jugular venous distension
ion pulmonary edema - Painful hepatosplenomegaly
- Dyspnea, paroxysmal nocturnal dyspnea (increased with characterstic 'nutmeg
venous return while lying flat), orthopnea (SOB while liver'
flat), crackles in lung - Cardiac cirrhosis
- Hemosiderin laden macrophage in lung (aka heart - Pitting edema
failure cells) - pulmonary capillaries burst due to
backing up
- Decreased flow to kidney activates RAS which leads
to fluid retention and worsens CHF
Treatmen ACE inhibitors
t

Cardiac Page .1

8.3 Congenital Defects

1. What is epidemiology of congenital heart defect?

- Occur during week 3-8 (organogenesis)
- Seen in 1% of live births
- Most diseases are sporadic
- Most common congenital heart defect is VSD

2. If there's a left-right shunt in heart, which direction does it initially present? Why does it reverse?
- Early shunt is left to right due to reduced resistance in pulmonary circulation.
- Shunt later becomes right to left - pulmonary circulation increases resulting in pulmonary HTN and
hypertrophy of pulmonary vessels

3. What is Eisenmenger syndrome (aka tardive cyanosis)?

- Serious hypoxemia caused by reversal of left-to-right shunt is called Eisenmenger syndrome.
- It can be present during atrial septal defect, VSD or patent ductous arteriosus

4. What are presentation of Eisenmenger syndrome?

- Right ventricular hypertrophy
- Polycythemia vera (increased RBC to combat hypoxemia)
- Clubbing, cyanosis

VSD
1. What's most common congenital heart defect? What is it associated with (HY)?
- Ventricular septal defect
- It's associated with fetal alcohol syndrome

2. How does it present?

- Early on, the shunt is left to right, later on it becomes right to left.

3. How is it treated?
- Small defects close spontaneously. Surgery for large defects.

Cardiac Page .1

 - Small defects close spontaneously. Surgery for large defects.

ASD
1. What are types of atrial septal defects?
- Ostium secundum (most common) - hole between atria. Ostium is primitive membrane that
divides heart to left and right sides.
- Ostium primum (aka endocardial cushion defect) -
○ ASD + valve defect + defect in intraventricular wall.
○ Endocardial cushion - junction of atrial septum, ventricular septum, tricuspid and mitral
valves.
○ Most associated heart defect with Down's syndrome
- Sinus venosus

Fig: osteum primum (left), osteum secundum (middle and right)

2. What's ASD presentation? What's an important complication?

- Split S2 sound: due to increased blood in right heart, pulmonic valve closes late.
- Paradoxical emboli are important complication - ex - DVT emboli will go to brain instead of lungs

PDA
1. What is patent ductous arteriosus? What's it associated with?
- Failure of ductous arteriorus to close after birth.
- Associated with congenital rubella
- Presents with left to right shunt between aorta and pulmonary artery. Later on, the shunt
becomes right to left due to pulmonary HTN and hypertrophy of pulmonary vessels

2. What's it's presentation?

- Asymptomatic at birth but has 'machine-like murmur'
- May lead to Eisenmenger syndrome results in lower extremity cyanosis (because ductus arteriosus
happen after upper extremity branching)

Cardiac Page .2

 happen after upper extremity branching)

3. What's it's treatment?

- Indomethacin - decreased PGE. PGE kEEEps PDA open.

Tetralogy of fallot
1. What is tetralogy of fallot?
- Stenosis of right ventricular outflow tract
- Right ventricular hypertrophy
- VSD
- Aorta that overrides the VSD
- Right to left shunt. Almost all others are left to right in the beginning.

2. What's it's presentation?

- Early cyanosis due to right-to-left shunt (more stenting = more cyanosis)
- Usually after exercise, pt squat to increase pulmonary blood flow (squatting increases systemic
resistance)
- Boot shaped heart on X-ray

Fig: boot shaped heart indicating tetralogy of falot

Transposition of great vessels

1. What is transposition of great vessels?
- Aorta arises from right ventricle and pulmonary artery arises from left ventricle. Right side does

Cardiac Page .3

 - Aorta arises from right ventricle and pulmonary artery arises from left ventricle. Right side does
systemic circulation and left side does pulmonary curculation
- Left and right sided blood never mix (early cyanosis)

2. What's it's presentation? What's it associated with? How do you treat?

- Presentation:
○ Early cyanosis (right and left sided blood don't mix)
○ Right ventricle hypertrophy and atrophy of left ventricle
- Treatment:
○ Create a shunt after birth is required for survival
○ Administer PGE (PGE kEEEps PDA open)
- Association:
○ Maternal diabetes

Truncus arteriosus
1. What is truncus arteriosus?
- It's when a single large vessel arises from both ventricles. (truncus fails to divide to aorta and
pulmonary artery)
- Presentation:
○ Early cyanosis

Tricuspid atresia (atresia means fail to form a tube)

1. What's tricuspid atresia? How does it present?
- It's failure of development of orifice of tricuspid valve.
- Presentation:
○ Hypoplastic right ventricle (ASD and VSD often present)
○ Early cyanosis
- Association:

Cardiac Page .4

 - Association:
○ ASD alone or ASD + VSD

Coarctation of aorta
1. What's coarctation of aorta? What are two types?
- Coarctation of aorta is narrowing of aorta
Infantile type Adult type
Anatomy Narrowing is after aortic arc but before PDA Narrowing is after aortic arch (not
associated with PDA; if PDA
present, it's infantile type)
Associati Associated with PDA and Turner syndrome (one Associated with bicuspid aortic
on X, no Y) (HY) valve (HY)
Presenta Presents as lower extremity cyanosis in infants, - Presents as HTN in upper
tion often at birth - due to coarctation, lower extremitties and hypotension with
extremity isn't supplied by LV but by RV. Upper weak pulse in lower extremities;
extremities are fine because LV supplies there often discovered in adulthood
- Collateral circulation across
intercostal arteries causes
engorged artieries and notching on
ribs on X-ray (HY)

Cardiac Page .5

Cardiac Page .6
8.4 Valvular Disorders

Acute rheumatic fever

1. What is pathogenesis of actue rheumatic fever?
- It's a systemic complication of group A strep which presents 2-3 weeks after streptococcal
pharyngitis
- Bacterial M protein mimics human protein and autoantibodies are generated.

2. How is acute rheumatic fever diagnosed?

- Diagnosis is based on evidence of group A strep infection (elevated ASO or anti-DNAse B titer) +
major (JONES) or minor criterea
- Minor criteria
○ Fever and elevated ESR (non-specific)
- Major criteria (JONES)
○ Joint (migratory polyarthritis) - swelling in pain in large joints (wrist, knee, ankle) that
resolve in days and move to another large joint
○ O (pancarditis)
 Endocarditis - Mitral valve is most commonly affected. See small vegetations along
line of closure that lead to regurgitation
 Myocarditis - Aschoff bodies seen (focal area of chronic inflammation). Presence of
Anitschkow cells (reactive histiocytes with slender, wavy nucleus), fibrinoid material
and giant cells. (myocarditis most common cause of death)
 Pericarditis - friction rub and chest pain
○ Subcutaneous Nodules
○ Erythema marginatum - nonpruritic rash with erythematous border commonly on trunk and
limbs
○ Sydenham chorea

3. What is most common cause of death in acute rheumatic fever?

- Myocarditis

4. What is prognosis of acute rheumatic fever?

- Acute attack usually resolvs but may progress to chronic rheumatic heart disease
- Repeat exposure with group A strep increases chance of rheumatic heat disease

Chronic rheumatic fever

1. What's presentation of chronic rheumatic fever?
- Mitral valve is most commonly affected, aortic valve is no. 2; other valves rarely affected
- Mitral valve - classic fish mouth appearancedue to stenosis (valve can't open well)
- Aortic valve - fusion of commissures

2. What's a complication of chronic rheumatic fever?

Cardiac Page 4.1

 2. What's a complication of chronic rheumatic fever?
- Infective endocarditis

Aortic stenosis
1. What are some causes of aortic stenosis?
- Normal wear and tear of valve
- Bicuspid aortic valve (speeds up wear and tear)
- Chronic rheumatic fever

2. What is its presentation?

- Presents in late adulthood (>60 years)
- Crescendo-decrescendo murmur with systolic ejection click (click is when the valve opens?)

3. How do you distinguish stenosis from chronic rheumatic fever vs normal wear and tear?
- In chronic rheumatic fever, there is fusion of commissures of aortic valves. Also, we see mitral
stenosis.

4. What are complications of aortic stenosis?

- Concentric left ventricular hypertrophy - may progress to cardiac failure
- Angina with syncope with exercise (decreased perfusion of heart and brain)
- Microangiopathic hemolytic anemia (see schistocytes)

5. How do you treat aortic stenosis?

- Valve replacement

Aortic regurgitation
1. What are causes of aortic regurgitation?
- Isolated aortic root dilation (most common cause)
- Aortic dissection, Syphillis (causes aortic root dilation)
- Valve damage, ex - infective endocarditis

2. What are clinical features of aortic regurgitation?

- Increased pulse pressure (water-hammer pulse) - diastolic pressure is low due to regurgitation,
systolic pressure increases due to increased stroke volume (pulse pressure is difference between
systolic and diastolic pressures)
- LV dilation and eccentric hypertrophy due to volume overload

3. What is treatment of aortic regurgitation?

- Valve replacement once LV dysfunction develops

Cardiac Page 4.2

Mitral valve prolapse
1. What is mitral valve prolapse? What are some etiologies?
- Mitral valve prolapse is ballooning of mitral valve into left atrium during systole
- It occurs due to myxoid degenration of valve making it floppy
- Etiologies:
○ Marfan syndrome
○ Ehlers-Danlos syndrome

2. What is presentation of mitral valve prolapse?

- Mostly asymptomatic
- Mid-systolic click followed by regurgitation murmur
- Murmur is softer with squatting (increased systemic resistance decreases left ventricular
emptying)

3. What are complications?

- Rare but infective endocarditis, arrhythmia and severe mitral regurg

4. What is treatment of mitral valve prolapse?

- Valve replacement

Mitral regurgitation
1. What are some causes of mitral regurgitation?
- Complication of mitral prolapse
- LV dilation
- Infective endocarditis
- Acute rheumatic fever - vegetation on valve edge prevent smooth closing
- Papillary muscle rupture after MI

2. What is presentation of mitral regurgitation?

- Holosystolic "blowing" murmur; lower when squatting (increased systemic resistance decreases
LV emptying) and expiration (increases blood return to LV)
- Volume overload and left sided failure

Mitral stenosis
1. What are some causes of mitral stenosis?
- Chronic rheumatic valve disease most common cause

2. What are presentations of mitral stenosis?

- Opening snap followed by diastolic rumble
- Volume overload with dilation of left atrium:
○ Pulmonary congestion with edema and alveolar hemorrhage
○ Pulmonary HTN and eventual right sided heart failure
○ A-fib with mural thrombus

Cardiac Page 4.3

8.5 Endocarditis

1. What is endocarditis?
- Inflammation of endocardium (mostly valves) usually due to bacterial infection.

Pathogen
1 S. viridans Most common cause of Subacute endocarditis (small
endocarditis; dental vegetations)
procedure
2 S. aureus Most common cause of Acute endocarditis (large
endocarditis in IV drug vegetations)
users
3 S. epidermidis Key organism to cause
endocarditis of prosthetic
valves
4 Strep bovis Cause endocarditis in pt
with colorectal carcinoma
(HY)
5 HAECK organism Hemophilus, Cause endocarditis with negative
Actinobacillus, blood culture (because
Cardiobacterium, pathogens difficult to grow)
Eikenella, Kingella
6 Nonbacterial Occurs if pt is
thrombotic hypercoagulable or has
endocarditis adenocarcinoma
7 Libman-Sacks Sterile vegetations on Associated with lupus
endocarditis both side of mitral valve
8 Coxiella burnetti Most common cause of
culture -ve endocarditis
1. Describe endocarditis due to S. viridans.
- Most common cause of endocarditis.
- Low virulence pthogen; therefore mainly infects previously damaged valves
- Results in small vegetations that don't destroy valves (therefore called subacute endocarditis)

3. Describe pathogenesis of endocarditis due to S. viridans.

- Damaged endocardial surface develops thrombotic vegetations
- During transient bacteremia (ex - dental procedure), bacteria can be trapped in these vegetations

4. Describe endocarditis due to S. aureus.

- Most common cause of endocarditis in IV drug abusers
- High virulence organism; can infect normal valves (mainly tricuspid)
- Vegetations are large and destroy valve (called acute endocarditis)

Cardiac Page 5.1

 Fig - staph aureus endocarditis

5. Describe clinical presentation of endocarditis. (FOR JANE)

- Fever
- Murmur
- Janeway lesion - mainly on palm and sole (painless)
- Osler nodules (hurts - ouch!) - mainly on finger and toes (painful)
- Roth nodules
- Hemolytic anemia (usually microcytic)
- Nailbed splinter hemorrhage
- Emboli

Fig - roth nodules (retinal hemorrhage); osler and roth nodules are immunologic.

Endocarditis may lead to glomerulonephritis and positive Rheumatic factor.

6. How does endocarditis lead to low blood iron.

- Acute phase reactant proteins are made (hepsidin being one major one). Hepsidin traps iron in
storage site. This leads to high ferritin. Also, bone marrow takes iron from blood because hepsidin
is trapping iron in storage site. That’s how serum iron decreases.

7. Describe nonbacterial thrombotic endocarditis.

- It is sterile vegetation seen on valves during hypercoagulable state or underlying adenocarcinoma.

Cardiac Page 5.2

 - It is sterile vegetation seen on valves during hypercoagulable state or underlying adenocarcinoma.
- These vegetations occur on bicuspid valves along lines of closure and lead to mitral regurg

8. Describe Libman-Sacks endocarditis.

- Sterile vegetations on both side of mitral valve - leads to mitral regurg
- Associated with lupus (HY)

9. Describe diagnosis of endocarditis.

- Surface Echo - 60% sensitive
- Transesophageal echo - 90% sensitive

- Endocarditis leads more often regurg of valves rather than stenosis

- If valve vegetation is >1cm, consider surgery of valves

Cardiac Page 5.3

8.6 Cardiomyopathy

1. Describe dialated cardiomyopathy.

- Most common type of cardiomyopathy
- Leads to systolic dysfunction (heart can't contract very well)
- Complications:
○ mitral and tricuspid regurg
○ Arrhythmia (heart's conduction system is stretched up)

2. What are some causes of dialated cardiomyopathy?

- Idiopathic in most cases
- Mutation - they are autosomal dominant
- Myocarditis - coxcakie virus most common pathogen
- EtOH abuse (HY)
- Drugs - doxorubicin, cocaine
- Pregnancy (HY) - occurs in 3rd trimester or soon after birth

Fig - myocarditis; notice the presence of lymphocytes. Most common cause is coxcakie virus;
acutely, it can cause death; in chronic cases, it can cause dialated cardiomyopathy

3. What is treatment for dialated cardiomyopathy?

- Nothing; pt need transplant

Hypertrophic cardiomyopathy
4. Describe hypertrophic cardiomyopathy.
- Massive hypertrophy of left ventricle
- Most common cause (HY): due to autosomal dominant mutations in sarcomere proteins

5. What are its clinical presentation?

- Diastolic dysfunction (heart doesn't fill well)
- Sudden death in young athletes due to ventricular arrhythmias.
- Syncope with exercise
- Biopsy (HY):
○ Myofiber hypertrophy with disarray

Cardiac Page 6.1

 Fig - myofiber hypertrophy and disarray (fibers oriented in different directions)common in
hypertrophic cardiomyopathy

Restrictive cardiomyopathy
6. What is restrictive cardiomyopathy and it's causes?
- Diastolic dysfunction
- Causes
○ Amyloidosis
○ Sarcoidosis
○ Hemochromatosis
○ Endocardial fibroelastosis (in kids) - there's fibrosis and elastosis in endocardium
○ Loeffler syndrome - eosinophilic inflammation of endocardium and myocardium

7. What is EKG finding of restrictive cardiomyopathy?

- Low voltage EKG
- Diminished QRS amplitudes

Cardiac Page 6.2

8.7 Cardiac Tumors

Myxoma Rhabdomyoma Metastasis

Most common cardiac tumor in
adults
Benign mesenchymal tumor with
abundant ground substance in
histology
Pedunculated mass in left atrium
Most common cardiac Most common cardiac tumor
tumor in children
Benign hamartoma of
cardiac muscle
Usually seen in ventricle Most commonly affects pericardium
and seen as pericardial effusion

Associated with tuberous Breast, lung carcinoma, melanoma and

sclerosis lymphoma common source of
metastasis
Myxoma
1. What is most common primary cardiac tumor in adults?
- Myxoma

2. What type of tumor is myxoma?

- Benign mesenchymal tumor with abundant ground substance in histology

2. What is its presentation?

- Pedunculated mass in left atrium that can obstruct mitral valve (syncope)

Fig: biopsy (abundant ground substance) and autopsy of myxoma

Rhabomyoma
1. What is most common primary cardiac tumor in children?
- Rhabdomyoma

Cardiac Page 7.1

 2. What kind of tumor is rhabdomyoma?
- Benign hamartoma of cardiac muscle
- Usually seen in ventricle

2. What is it associated with?

- Tuberous sclerosis (a genetic disorder that causes non-malignant tumors in many different organs,
primarily in the brain, eyes, heart, kidney, skin and lungs. Common presentation: seizures,
developmental delay, intellectual disability and autism)

Fig: rhabdomyoma

Metastasis
1. What is most common type of cardiac tumor?
- Metastasis (more common than primary tumors)

2. What are common sites of metastasis?

- Breast, lung carcinoma, melanoma and lymphoma

3. What is its most common presentation?

- Most commonly affects pericardium and seen as pericardial effusion

Cardiac Page 7.2