Pathoma-Lecture-Notes

6.3 Chronic Leukemia

1. What is chronic leukemia? What are it's types?
- Chronic leukemia is proliferation of MATURE circulating lymphocytes.
- It's usually seen in adults and have insidious onset.
- Types:

Cancer name Cell type high Remarks

Chronic lymphocytic Naïve B cells (CD5 - Most common leukemia overall
- See smudge cell (like someone smashed a cell in slide) -
leukemia (CLL) and CD20 +ve) - - See generalized lymphadenopathy
- Small lymphocytic lymphoma is a type of CLL that affects tissue
naïve kids smudge

their food

Complicati • Transformation to diffuse large B-cell lymphoma (richter
ons transformation) - see enlarging lymph nodes or spleen

• Hypogammaglobulinemia - INFECTION MOST COMMON
CAUSE OF DEATH

Associatio • Autoimmune hemolytic anemia
n

Picmonic:

CaLL - CLL

Epid - Most common leukemia in adults (old people in pic)

Presentati - Often asymptomatic - both elderly are happy and dancing
on - Smudge cell - cell smudged on glass of grandpa

Associatio - Autoimmune hemolytic anemia - both IgM and IgG - cold
n and warm sea anemone

Hairy cell leukemia Mature B cells (TRAP - Lymphadenopathy usually absent
(rare leukemia)
+ve (tartarate - Marrow fibrosis (dry bone marrow tap)

resistant acid

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resistant acid
phosphatase) and
hairy cytoplasm) -
hairs trap; mature
people are hairy

Picmonic:

Hairy guy with Basketball - hairy cell leukemia

Presentati - Splenomegaly (can be the only finding) - hairy cells
on accumulate in spleen - spleen baloon

- Lymphadenopathy usually absent

Treatment - Excelent response to 2-CDA (cladribine) - cloud ribbons

Adult T cell Mature CD4+ cells - Associated with HTLV-1; common in Japan and caribbean
- Skin rash, generalized lymphadenopathy, hepatosplenomegaly,
leukemia/lymphoma - lytic (punched out) bone lesion with hypercalcemia

Mycosis Fungoides Mature CD4+ cells - Excellent treatment to chemotherapy
(cutaneous T-cell that infiltrate skin
lymphoma) - See sezary cells (cerebriform nuclei) in blood smear
- CD4 accumulation in skin produces rash, plaques and nodules called
pautrier microabscess

Fig - Sezary cells, pautrier microabscss - microcospic and gross

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6.4 Myeloproliferative Disorders

1. What is myeloproliferative disorders? What's its presentation?
- Myeloproliferative disorders is neoplastic proliferation of mature cells of myeloid lineage
- Disease presents in late adulthood (50-60 years)
- Presentation:

○ Hypercellular bone marrow with increased WBC
○ All cells in myeloid lineage are increased, classification is based on what cell is dominantly

present

2. What are types of myeloproliferative disorders? What is characteristic mutation?

Disorder Dominant cell Mutation

Chronic myeloid Granulocytes (neutrophil, t(9;22) aka philadelphia
leukemia (CML) eosinophil, basophil); increased chromosome - present in 95% of pt
basophil (HY)

Polycythemia vera RBC JAK2 kinase mutation
(PV)

Essential Platelets JAK2 kinase mutation
thrombocythemia
(ET)

Myelofibrosis Megakaryocytes JAK2 kinase mutation (50% of cases)

Chronic myelogenous leukemia (CML)
1. What is the mutation that causes CML? What's treatment?
- T(9;22) produces philadelphia chromosome. It creates fusion of BCR on ch 22 with ABL receptor
tyrosine kinase protein. It leads to increased tyrosine kinase activitiy.
- Treatment
○ Imatinab - blocks tyrosine kinase activity (HY)
○ Hydroxyurea - inhibits ribonucleotide reductase (DNA synthesis) - prevent cell dividion
○ IFN alpha - increased destruction of cells
○ Hydroxyurea and IFN alpha can be used in many disease where cell divides too much

2. What is presentation and complication?
- Splenomegaly is common
- Complication:

○ Transformation to AML (2/3rd of cases)
○ Transformation to ALL (1/3rd of cases)

3. How do you diagnose CML?
- Peripheral blood smear shows leukocytosis - too much WBC
- FISH can be used to see philadelphia chromosome (seen in 95% of cases); however gene

translocation is seen in 100% of cases.

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4. How do you distinguish CML from lukemoid reaction (reactive neutrophilic leukocytosis)?

CML Lukemoid reaction

Negative leukocyte alkaline phosphatase Positive leukocyte alkaline phosphatase (LAP) stain
(LAP) stain (LAP present in normal
neutrophils but absent in malignant
neutrophils)

INCREASED BASOPHILS (HY) No increase in basophil
t(9;22) present t(9;22) absent

5. Picmonic for CML

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CML Camel
Mutation - t(9;22) - ninja and double tutu

- Makes philadelphia chromosome (philadelphia cream cheese)
- BCR-ABL fusion protein created - VCR - Abraham lincoln
Treatment - Imatinib - eye-mat

Polycythemia vera (PV)
1. What is PV?
- Increase in RBC, WBC and platelets but main presentation is based on too much RBC.

1. What are presentation of PV?
- Presentation based on increased viscosity of blood:

○ Flushed face due to congestion (plethora)
○ Intense itching, especially after bathing (due to histamine release from increased mast cells

due to heat)
○ Erythromelalgia - severe burning pain, and red-blue discoloration due to blood clots in

vessels of extremities; melalgia = buring pain in limbs
○ Hepatosplenomegaly (splenomegaly because there's too much RBC so amount of bad RBC

will be high and spleen has to eat them; hepatomegaly because liver makes RBC due to
mutation in JAK2 kinase).
○ Gout - proerythroblasts (RBC witn nucleus) will leak out and be eaten by spleen. Metabolism
of nucleus increases uric acid.
○ Venous thrombosis

 No. 1 cause of budd-chiari syndrome
 Dural sinus thrombosis
 Retinal vein thrombosis

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Fig: polycythemia presentation - from left to right: dural sinus thrombosis, Erythromelalgia, facial
plethora, itching, hepatosplenomegaly, gout

2. How do you treat PV?
- Phlebotomy (first line)
- Hydroxyurea - second line (inhibits ribonucleotide reductase - DNA synthesis)
- Interferon alpha - increased destruction of proerythroblasts (can induce gout)

3. What's prognosis of PV?
- Death within a year without treatment

4. How do you distinguish PV from reactive polycythemia?

PV Reactive polycythemia

Normal SaO2, low erythropoietin - If due to lung disease or high altitude- Low SaO2, high
(EPO) EPO
- If due to ectopic EPO production, SaO2 normal, high EPO

Essential thrombocythemia vs Myelofibrosis
1. Differentiate essential thrombocythemia vs myelofibrosis

Essential thrombocythemia (ET) Myelofibrosis

Neoplastic proliferation of platelets - Neoplastic proliferation of megakaryocytes
megakaryocytes divide too much. (megakaryocyte = cell with big nucleus)
Thrombocyte = platelet

Associated with JAK2 kinase mutation Associated with JAK2 kinase mutation

Presentation Presentation:
- increased risk of thrombosis and/or - Increased risk of thrombosis and/or bleeding,
bleeding (low platelet due to too infection
much thrombosis) - Hepatosplenomegaly - they will produce blood
- Splenomegaly - spleen has to eat cells as marrow is fibrosed (MOST COMMON
too much platelets CAUSE OF SPLENOMEGALY IN PT >55 YEAR
- Rarely progress to marrow fibrosis OLD)
or acute lukemia - Marrow fibrosis (due to PDGF production from
- Rare risk for hyperuricemia or gout megakaryocytes) will impinge on bone and

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- Rare risk for hyperuricemia or gout megakaryocytes) will impinge on bone and
(only platelets are increased which cause bone pain
don't have nucleus) - Splenomegaly due to extramedullary
hematopoiesis (due to marrow fibrosis)
• Enlarged megakaryocytes in bone - Leukoerythroblastic smear (tear drop RBC - RBC
marrow biopsy squeezing through fibrosed marrow, nucleated
RBC, immature granulocytes)

Fig: leukoerythroblastic smear, marrow fibrosis

- Diagnosis: - Diagnosis:
• Diagnosis of exclusion • Tear drop RBC
• See platelets >450k for >2 months • Bone marrow tap will be dry; see fibrosis in
biopsy

- Treatment: - Treatment:
• Asprin for low risk pt to prevent • Stem cell transplant - replace fibrosis
clot • Transfusion to give blood cells that’s missing
• Hydroxyurea , interferon alpha to
reduce megakaryocyte formation
• Plateletpheresis - take excess
platelet from circulation in
emergency condition

- Leukoerythroblastic anemia is anemia due to space occupying lesion in marrow

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6.5 Lymphadenopathy (LAD)

1. When do you see painful vs painless lymphadenopathy?
- Lymphadenopathy is enlarged lymph nodes.
- Painful:

○ Lymph nodes draining a region of acute infection (acute lymphadenitis)
- Painless:

○ Chronic inflammation (chronic lymphadenitis)
○ Metastatic carcinoma
○ Lymphoma
2. What are indications depending on what part of lymph node is enlarged?
- Follicular enlargement (B cell region):
○ Rheumatoid arthritis
○ Early stages of HIV
- Paracortex enlargement (T cell region):
○ Viral infection (ex - EBV)
- Sinus histiocytes enlargement:
○ Lymph nodes draining with cancer

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6.6 Lymphoma, 6.7 Hodgkin Lymphoma

1. What is lymphoma?
- Neoplastic proliferaion of lymphoid cells that makes a mass; may arise in lymph node or extranodal tissue.

2. Distinguish Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).

Hodgkin lymphoma Non-Hodgkin lymphoma

Frequency 40% 60%

Malignant cells Reed-Sternberg cells (owl eye cells) - B cells - Lymphoid cells - many subtypes - most are B cell

induce inflammation and fibrosis than T cells

Mass Inflammatory cells and fibrosis (reactive cells) Lymphoid cells
composition

Clinical - Painless lymphadenopathy - Painless lymphadenopathy
- B symptoms - Classically seen in late adults
- Bimodal: classically seen in young adult
and >55 yrs

Spread Contiguous (touching); rarely extranodal Diffuse; often extranodal

Staging Guides therapy Limited importance
Radiation mainstray treatment

Leukemic phase Doesn't occur Occurs

Prognosis Much better prognosis than non-Hodgkins

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Association EBV HIV and autoimmune diseases

Hodgkin lymphoma (HL)
1. What are Reed-sternberg cells?
- Large B cells (CD 15 and CD 30 +ve) with multilobed nuclei and prominent nucleoli that looks like Owl eye
- They produce cytokines which attract inflammatory cells and cause fibrosis (can be seen in biopsy)

2. What are presentation of Hodgkin lymphoma?

- Due to cytokine release:
○ B symptoms - fever, chills, wt loss, night cells
○ Presence of reactive inflammatory cells that make bulk of tumor
○ Fibrosis

3. What are different subtypes of Hodgkin lymhoma and what are their characters?

Subtype Characters

Nodular sclerosis - Most common type of HL
- Classic pt is young adult female
- Presents as enlarged cervical or mediastinal lymph nodes
- Biopsy:

• Lymph node is divided by band of fibrosis
• Reed sternberg cells are present in lake like spaces (lacunar cells)

Fig: band of fibrosis (left), lacunar cells (a variant of Reed sternberg cells - right)

Mixed cellularity - Associated with abundant eosinophils (reed sternberg cells produce IL-5)

Lymphocyte rich - Best prognosis of all types

Lymphocyte depleted - Most aggressive of all types
- Usually seen in HIV pt or old pt

Non-Hodgkin lymphoma

1. What are types of non-hodgkin lymphoma?

- Non-hodgkin lymphoma is classified based on cell size, cell type (B or T), pattern of cell growth, cell surface markers,

translocations.

- Types:
○ Small B cells
 Follicular lymphoma - enlarged and too many follicles
 Mantle cell lymphoma - cancer of mantle (area around follicle)
 Marginal zone lymphoma - cancer of marginal zone (area around mantle)
 Small lymphocytic lymphoma (CLL that involve tissue)
○ Intermediate B cell lymphoma
 Burkitt lymphoma
○ Large B cells
 Diffuse large B-cell lymphoma

2. What are the causes of the different NH lymphoma? Remarks
NH lymphoma Cause

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NH lymphoma Cause Remarks

Follicular t(14;18) - BCL2 on ch 18 moves to Ig heavy chain locus on ch14 - Can progress to diffuse large B
lymphoma (BCL2 inhibits apoptosis by blocking Bax and bac from making cell lymphoma (presents as
channel in mitrochondrial membrane so cytochrome C can leak enlarging lymph node)
out)

Mantle cell t(11;14) - Cyclin D1 on ch 11 goes to Ig heavy chain locus on ch14 - Often present in late
lymphoma adulthood with painless
lymphadenopathy

Marginal zone - Chronic inflammatory state - Hashimoto thyroiditis, Sjogren - Marginal zone made of post-
germinal B cells
lymphoma syndrome, H pylori gastritis (causes MALToma - a type of
- Often present in child or young
marginal zone lymphoma) adult as extranodal mass:

Small - Chronic lymphocytic leukemia (naïve B cells; smudge cell) • African form - in jaws
lymphocytic affecting tissue • Sporadic form - in
lymphoma
abdomen
Burkitt - t(8;14) - c-myc on ch 8 goes to Ig heavy chain locus on ch14 (myc
lymphoma is a protein in RAS-MAPK pathway - cellular proliferation and
increased cyclin D production)
- Associated with BV infection
- Biopsy finding

Fig: starry sky appearance (night sky made of dark lymphocytes;
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Fig: starry sky appearance (night sky made of dark lymphocytes;
bright stars made up of mitotic figures)- left; right - african form
appearing on jaws

Diffuse large - Arise sporadically or transformation of low grade lymphoma (ex- - Most common NHL
B-cell follicular lymphoma, chronic lymphocytic leukemia) - High grade (aggressive)
lymphoma - Present in late adulthood as
extranodal mass or enlarging
lymph nodes

3. How do you distinguish follicular lymphoma from reactive follicular hyperplasia?

Follicular lymphoma Reactive follicular hyperplasia

- Cells are monoclonal - Cells are polyclonal

- Bcl2 expression in follicles (Bcl2 - anti-apoptotic - No Bcl2 expression in follicles
protein)

- Disruption of lymph node architecture - Preservation of lymph node architecture

- Lack of tingible body marcophage in germinal - Presence of tingible body marcophage (they eat bad B cells

center produced during somatic hypermutation)

Fig: bad lymph node architecture (follicles
present not only in cortex)

Fig: left (follulicular lymphoma lacking tingible body macohpage);
right (follicular hyperplasia with tingible body macrophage)
4. What's treatment of follicular lymphoma?
- Rituximab (anti-CD20 antibody) or low dose chemotherapy

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6.8 Plasma Cell Disorders (dyscrasias)

Multiple myeloma
1. What is multiple myeloma? What is molecular mechanism?
- MM is malignant proliferation of plasma cells in bone marrow. It's most common primary
malignancy of bone.
- Serum IL-6 (aka RANK-L) may be increased that induces plasma cell growth and Ig production.

2. What are clinical features of MM?

Bone pain with - Plasma cell produce IL-6 (RANK-L) that binds to RANK on
hypercalcemia osteoclasts (bone breaks down) - creates punched out lesions
mainly on skull and vertebra

Elevated serum protein (M - Classically due too much IgG (55% of cases) or IgA (25%)
spike present in serum production
protein electrophoresis -
SPEP)

Increased risk of infection - Even though too much Ig produced, lack of Ig specificity

Rouleaux formation on - Increased serum protein decreases charge between RBC and RBC
blood smear makes stacks
(rouleau = cylindrical
packet of coins)

Anemia • Plasma cells crowd out bone marrow so little RBC synthesis

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Primary AL amyloidosis - Due to too much Ig light chain (they deposit in tissue)

Proteinurea and renal - Free light chain protein excreted in urine as Bence Jones protein
failure - Light chain deposition in kidney can cause renal failure

Fig: Bence Jones crystal (see in Waldenstrom macroglobulinemia
too)

• Mnemonic CRAB
○ HyperCalcemia
○ Renal involvement / Roulex formatin
○ Anemia / Amylodosis
○ Lytic Bone lesions

Monoclonal Gammopathy of undetermined significance (MGUS)
1. What is MGUS? What's its significance?
- Increased serum protein with M spike on serum protein electrophoresis but no other feature of
MM (- no CRAB - no lytic bone lesion, no hypercalcemia, no rouleaux, no Bence Jones proteinura
etc)
- Significance:
○ Common in elderly (5% of >70 year old people)
○ 1% of pt with MGUS progress to multiple myeloma each year

Waldenstrom Macroglobulinemia
1. What is Waldenstrom macroglobulinemia? What are clinical features? What is treatment?
- B cell lymphoma with monoclonal IgM production (M for Macroblobulinemia)
- Clinical features:
○ M spike present - due to hyper IgM
○ Presentation based on hyperviscosicity of blood due to IgM pentamer (no CRAB findings
present)
▪ Retinal hemorrhage and stroke
▪ Bleeding - high blood viscosity leads to defective platelet aggregation
▪ Raynaud phenomena

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○ Generalized lymphadenopathy
- Treatment:

○ Plasmapheresis to remove IgM from serum

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6.9 Langerhans Cell Histiocytosis

1. What is langerhans cell histiocytosis? What is histology finding?
- It is neoplastic proliferation of Langerhans cells (dendritic cells in skin and mucus membrane derived from monocytes).

Histiocyte = tissue macrophage
- Histology finding:

○ Characteristic Birbeck (tennis racket) granules on electron microscopy
○ Cells are CD1a and S100 +ve by imunohistochemistry

Fig: Birbeck granules characteristic of Langerhans cell histiocytosis

2. Describe clinical features of different types of langerhans cell histiocytosis.

Disease Clinical presentations

Letterer-Swie disease (acute disseminated Malignant - Rapidly fatal due to multiple organ involvement
langerhans cell histiocytosis) proliferation of - Classic pt is <2 year old infant
Langerhans cells - Presentation:

• Skin rash
• Cystic skeletal defect

Eosinophilic granuloma Benign - Classic presentation is pathologic fracture in
Hand-Schuller-Christian disease proliferation of adolescents
Langerhans cells - Skin is not involved
in bone - Biopsy shows langerhans cells with mixed inflammatory
cells and lots of eosinophils
Malignant
proliferation of - Classic pt is >3 year old
Langerhans cells - Presentation:

• Skull rash, Lytic skull defect
• Diabetes insipidus
• Exopthalmos

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• Exopthalmos
- Classic features:

○ If you see person's name, it's malignant and you see rash
○ if disease has 2 person's name, pt is <2 year old
○ If disease has 3 person's name, pt is >3 years

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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

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• 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.

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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

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• 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.

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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.

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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

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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.

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- 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
- Cardiogenic shock
<4 hrs none none - CHF
- Arrhythmia
4-24 hrs Coagulative Dark discoloration
necrosis - Arrhythmia (it doesn't happen post 24 hrs
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

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

pallor scar

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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

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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)

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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

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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

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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.

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- 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)

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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

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- 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:

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- Association:
○ ASD alone or ASD + VSD

Coarctation of aorta Adult type
1. What's coarctation of aorta? What are two types?
- Coarctation of aorta is narrowing of aorta Narrowing is after aortic arch (not
Infantile type associated with PDA; if PDA
Anatomy Narrowing is after aortic arc but before 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,
tion often at birth - due to coarctation, lower - Presents as HTN in upper
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)

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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?

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