Robbins - Ch 11 Flashcards
The basic constituents of the walls of blood vessels are 1 and 2 admixed with a variety of extracellular matrix, including elastin, collagen, and 3.
- Endothelial cells
- Smooth muscles
- Glycosaminoglycans
What are the three layers that make up arteries and veins?
Intima, media, and adventitia. These layers are most distinct in arteries.
which vessels are the principal points of physiologic resistance to blood flow?
Arterioles
1 is a vascular anomaly that is characterized by saccular outpouching, that typically occurs in the circle of willis, and has an association with autosomal dominant polycystic kidney disease. The single biggest worry of this anomaly is 2.
- Berry aneurysm
2. Rupture can cause fatal subarachnoid hemorrhage
T or F: A-V fistulas is always due to developmental defect.
False. It’s most commonly a developmental defect, but may arise secondary to inflammation, trauma or rupture.
A-V fistulas come to clinical concern when _
- rupture that can lead to subarachnoid hemorrhage
- Large or multiple AV fistulas can produce clinically significant effects by shunting blood from arterial to the venous circulation forcing heart to pump more and leading to high output cardiac failure
1 is a focal irregular thickening in medium and large muscular arteries, classically presents as 2, can also occur in _3_vessels. First degree relatives are at increased risk. On x-ray they appear as 4. Prevalence is common in 5.
- Fibromuscular dysplasia.
- Renal artery stenosis
- Carotid, splanchnic, vertebral
- Beads on a string
- young women
Endothelial cells normally maintain a nonthrombogenic surface under normal conditions but become activated due to certain stimuli. Name some stimuli that which can lead to an activated endothelial cell.
- Turbulent blood flow
- HTN
- Complement, bacterial product, lipid product, glycation end product
- Virus
- Hypoxia, acidosis
- Components of tobacco smoke
When endothelial cell become activated due to a stimuli, what changes are seen?
- expression of adhesion molecules
- Expression of procoagulants and anticoagulants
- expression of vasoactive factors, growth factors, chemokines, cytokines
What is meant by endothelial dysfunction?
Normally, endothelial cells can cycle between basal and activated states, to respond to various stimuli but when certain stimuli are consistently present, the prolonged activated state can lead to endothelial dysfunction characterized by procoagulation, proinflammation, and smooth muscle stimulation
_ is the stereotypical response of the vessel wall to any insult.
Intimal thickening, potentially affecting blood flow.
Sustained diastolic pressure above _ mmHg or sustained systolic pressure above _ mmHg is considered hypertension and is at increased risk of atheroscleortic disease.
89 and 139. Makes up about 30% of the population
90-95% of HTN are 1 and 5% are _ 2_
- Idiopathic or essential
2. secondary HTN due to underlying renal or adrenal disease, renal artery stenosis, or other.
Risk factors for essential HTN include:
- High Na intake
- stress
- obesity
- smoking
- physical inactivity
Blood pressure is a function of 1 and 2, both of which are influenced by multiple genetic and environmental factors, and is modified and maintained by the 3
- Cardiac output (CO)
- Peripheral vascular resistance (PVR)
Mean arterial pressure (MAP) = CO x TPR
- renin-angiotensin-aldosterone system (RAAS)
CO is a function of _ and _.
Stroke volume (SV) and heart rate (HR)
The most important determinant of stroke volume is 1, which is rgulatd through 2 homeostatis
- filling pressure
2. Sodium
Heart rate and myocardial contractility is mainly regulated by _ and _ systems which also have important effects on vascular tone.
alpha and beta adrenergic systems
Peripheral vascular resistance is regulated predomiantly at the level of which vessels and by what?
arterioles by neural and hormonal inputs
What are some vasodilactors and vasoconstrictors?
Vasodilators: kinins, prostaglandins, and NO)
Vasoconstrictors: angII, catecholamines, and endothelin
In states of low volume, or low peripheral resistance, or a decreased glomerular filtration rate, 1 is released by 2 in the _ 3_ arterioles in the kidney
- renin
- JG cells
- afferent
Describe some of the roles of vascular smooth muscle cells.
- Migrate and proliferate in response to mediators
- Elaborate cytokines and growth factors
- Synthesize and remodel extracellular matrix
- Cause vasoconstriction or dilation in response to physiologic or pharmacologic stimuli
what is neointima?
Injured endothelium and underlying vessel wall heals by stimulating smooth muscle cell ingrowth and exracellular matrix production leading to intimal thickening
This type of hypertension is characterized by systolic pressure more than 200 mm Hg, diastolic pressure more than 120 mm Hg, can lead to renal failure, retinal hemorrhage and if is left untreated can lead to death in 1 to 2 years.
Malignant hyertension
Blood volume is affected by what factors?
- Sodium
- Mineralocorticoids (aldosterone)
- Natriuretic factors that induce Na excretion
What is Liddle syndrome?
Gain of function mutation in an epithelial Na channel protein that increase distal tubular reabsorption of Na in response to aldosterone. —> secondary hypertension
Hypertension is associated with what two forms of small arteriolar disease?
Hyaline ateriolosclerosis and hyperplastic arteriolosclerosis
Describe the pathology of hyaline arteriolosclerosis
Endothelial cell injury with plasma leakage into arteriolar walls and increased smooth muscle cell matrix synthesis. Appears as diffuse pink hyaline on thickened arteriolar wall –> luminal stenosis
_ is usually seen in malignant hypertension and appears as concentric laminated (onion skin) arteriolar thickening with basement membrane and smooth muscle cell proliferation
Hyperplastic arteriolosclerosis
The intimal thickening as seen in hyaline arteriolosclerosis is made up or _
amorphous numerous plasma proteins that have leaked through.
The most common cause of secondary hypertension is _
Primary hyperaldosteronism due to a gene defect affecting enzymes involved in aldosterone metabolism.
Factors that are though to be contributory to essential hypertension include:
- Genetic factors that which alters net sodium reabsorption
- reduced renal Sodium excretion –> increase in fluid volume –> increase CO, peripheral vasoconstriction –> elevated BP. “resetting of pressure natriuresis” at the expense of increase BP
- Vasoconstrictive influences such as increased peripheral resistance
- Environmental factors such as smoking, obesity, physical inactivity, heavy salt intake
In _ due to chronic HTN, the arteriolar narrowing of hyaline arteriosclerosis causes diffuse impairment of renal blood supply and cause diffuse impairment of renal blood supply and glomerular scarring
Nephrosclerosis
The onion-skin like thickening as seen in hyperplastic arteriolosclerosis is accompanied by 1 deposits and vessel wall necrosis (necrotizing arteriolitis), particularly seen in 2
- fibrinoid
2. Kidney
Hardening of arteries is termed as
arteriosclerosis, characterized by wall thickening and loss of elasticity.
what are the three general patterns of arteriosclerosis?
- Arteriolosclerosis which affects small arteries and arterioles and may cause ischemic injury via hyaline or hyperplastic changes
- Monckeberg medial sclerosis: calcification of walls of muscular arteries typically involving internal elastic membrane. do not encroach lumen and so not significant
- Atherosclerosis - hardening and most clinically important
Atherosclerosis is a slowly progressive disease of which vessels?
large to medium sized muscular and elastic arteries.
What is atheromas?
Aka atheromatous or atherosclerotic plaques that protrude into vessel lumens. It consists of a raised lesion with a soft grumous core of lipid (mainly cholesterol) covered by a fibrous cap.
How does atherosclerosis cause pathology?
- Mechanically disrupt flow
- Plaque rupture leading to vessel thrombosis
- Weakening the underlying vessel wall and leading to aneurysm formation
What are the 4 major/classic risk factors leading to ahterosclerosis?
- Hyperlipidemia (esp LDL)
- HTN
- Smoking
- Diabetes
What are some nonmodifiable (constitutional) risk factors for atherosclerosis?
- Genetic abnormalities (hypercholesterolemia)
- Age (increased risk with age) between 40-60 risk of MI increase 5x.
- Gender: male more than women. Women more at risk after menopause (
Up to 20% of all cardiovascular events occur in the absence of major risk factors. Describe some of the additional risk factors.
- Inflammation (linked to atherosclerotic plaque formation/rupture). CRP can be measured as a marker
- hyperhomocystinemia (serum levels correlate with coronary atherosclerosis, peripheral vascular disease stroke and venous thrombosis)
- Metabolic syndrome (central obesity-insulin resistance, dyslipidemia, HTN) hypercoagulability.
- Lipoproteins: an altered form of LDL
- Hemostatic factors (Factor V leiden, elevated plasminogen activator inhibitor 1, platelet derived factors, thrombin etc)
Early lesions composed of intimal collections of foamy macrophages and smooth muscles cells that gently protrude into the vascular lumen is known as _
fatty streak
In the pathogenesis of atherosclerosis, describe the response to injury model.
Views atherosclerosis as a chronic inflammatory and healing response of arterial wall to endothelial injury. Lesion progression occurs through interaction of modified lipoproteins, monocytes-derived macrophages, and T lymphocytes with endothelial cells and smooth muscle cells of the arterial wall.
Explain the sequence of events in the atherosclerosis progression.
- Endothelial injury and dysfunction, causing increased vascular permeability, leukocytes, adhesion, and thrombosis
- Accumulation of lipoproteins
- Monocyte adhesion to endothelium then migration to intima and transformation into macrophages and foam cells
- Platelet adhesion
- Factor released from activated platelets, macrophages, and vascular wall cells, inducing smooth muscle cell recruitment
- Smooth muscle cell proliferation, EC matrix production and recruitment of T cells
- Lipid accumulation
The two most important causes of endothelial dysfunction are
- Hemodynamic disturbances (plaque formation usually occur at openings of exiting vessels, branch points, posterior abd aorta due to flow disturbance that’s normally seen in these locations.
- Circulating lipids (increased LDL, decreased HDL and increased abnormal lipoproteins) (Hypercholesterolemia) -lipids taken up by macrophages and oxidized and modified and accumulates within macrophages –> foam cells –> secretes Il-1 –>recruits more macrophages and T cells.
In descending order, the most extensively involved vessels are_
- lower abd aorta
- Coronary arteries
- popliteal arteries
- internal carotid arteries
- circle of willis
Morphologically, atherosclerotic plaques have what three principal components?
- Smooth muscle cells, macrophages, and T cells
- Extracellular matrix, including collagen, elastic fibers, and proteoglycans
- intracellular and extracellular lipid
Atherosclerotic plaques are susceptible to what clinically important pathologic changes?
- Rupture, ulceration, or erosion –> thrombosis
- Hemorrhage into a plaque
- Atheroembolism
- Aneurysm formation
Consequences of atherosclerotic disease include:
- Atherosclerotic stenosis
- Acute plaque change
- Thrombosis
- Vasoconstriction
- Vessel wall weakening
Critical stenosis is the stage at which the occlusion is sufficiently severe to produce tissue ischemia and typically occurs at when occlusion produces _% decrease in luminal cross sectional area.
70
What is acute plaque changes?
Plaque erosion, frank rupture, or hemorrhage into the plaque, which expands the plaque volume and can increase luminal stenosis
1 Plaques that are at increased risk of rupture and is characterized by large deformable atheromatous cores, thin fibrous caps, and/or increased inflammatory cell content. Whereas 2 have a core that is characterized by minimal atheromatous cores and thicker, well collagenized fibrous caps with little inflammation.
- vulnerable plaques
2. Stable plaques
what is a true aneurysm?
Saccular (one side) or fusiform (both sides) dilation of all three vessel wall layers
What is a false aneurysm/pseudoaneurysm?
An extravascular hematoma that communicates with the intravascular space (pulsating hematoma)
what is a arterial dissection?
when blood enters the arterial wall as a hematoma dissecting between layers. Often are aneurysmal, but not always
Aneurysm can occur whenever the connective tissue of the vascular wall is weakened, whether by acquired or congenital conditions. List and explain some factors that can lead to vascular weakening.
- Defective vascular wall connective tissue as seen in 1. marfan syndrome due to defective fibrillin synthesis; 2. Loeys-Dietz syndrome mutation in TGF-beta receptors leading to defective synthesis of elastin and collagens I and III; 3. Ehlers Danlos syndrome (defective collagen type III; 4. Scurvy vit C deficiency leading to poor collagen cross linking
- Imbalance of college degradation and synthesis, esp increased MMP, decreased TIMPs. Example in AAA, local production of cytokines (IL4, and 10) stimulate release of elastolytic MMP from macrophages
- loss of smooth muscle cells or synthesis of noncollagenous or nonelastic extracellular matrix (poor O2 diffusion due to increased diameter by which O2 must diffuse leading to degenerative changes of the media (cystic medial degeneration).
Explain how syphilis is implicated in aneurysm formation
Tertiary syphilis characterized by obliterative endarteritis shows predilection for small vessels including those of vasa vasorum. this leads to ischemic injury of the media and thus aneurysmal dilation
what are the two most important causes of aortic aneurysm?
atherosclerosis and HTN
Aneurysms due to infection are called 1, and can originate 2, 3, and_4.
- Mycotic aneurysm
- embolization of a septic embolus usually a complication of endocarditis
- extension of an adj suppurative process
- By circulating organisms
Abdominal aortic aneurysm (AAA) typical occur due to _
atherosclerosis. Frequently in male smokers over 50.
Although they’re uncommon, inflammatory AAA accounts for 5-10% of all AAA and occur in younger patients. Explain how these appear morphologically
Pt usually presents with back pain and elevated inflammatory markers like CRP. Grossly they are characterized by dense abundant lymphoplasmacytic inflammation with many macrophages associated with dense perioartic scarring that can extend into the anterior retroperirtoneum.
Pts with immunoglobulin G4 (IgG4)-related disease are also develop inflammatory AAA. Explain how the aneurysm arise and why it’s important to identify these aneurysm promptly.
Affected individual have aortitis and periaortitis that weaken the wall sufficiently and can give rise to aneurysms. Recognition is important since it responds well to steroid therapy
What complications are associated with AAA?
- rupture into peritoneal cavity —> fatal hemorrhage
- obstruction of a vessel branching off from the aorta
- Embolism from atheroma or mural thrombus
- impringement on another structure (ureter or verebrae
Risk of rupture of AAA is directly related to size. What size is at greater risk rupture?
6cm or larger
What sized AAA requires aggressive usually by surgical bypass with prosthetic grafts.
5cm or larger
What signs and symptoms do patients with thoracic aortic aneurysm present with?
- respiratory difficulties due to encroachment on lungs and airway
- difficulty swallowing
- persistent cough
- pain caused by erosion of bone
- cardiac disease as aortic aneurysm leads to aortic valve dilation with valvular insufficiency or narrowing of coronary ostia
- rupture
Pt with syphilitic aneurysm is most likely to die from _
heat failure secondary to aortic valvular incompetence
Where as AAA is more commonly due to atherosclerosis, Thoracic aortic aneurysm is more commonly due to
hypertension induced cystic medial degenerative. Less commonly congenital defect in connective tissue synthesis like in Marfans
Aortic dissection occurs mainly in two groups of patients:
- men aged 40-60 with antecedent HTN
- younger adults with systemic or localized abnormalities of connective tissues affecting the aorta like Marfans
Less common but can occur: iatrogenic: following arterial cannulation durign catheterization procedures or cardiopulmonary bypass; pregnancy 3rd trimester
The classic presentation of a patient with aortic dissection is _
severe chest pain, radiating to the back between the scapulae
The most serious complications of aortic dissection is when it involves what part of the aorta?
between the aortic valve and the distal arch.
Vast majority (and dangerous) of aortic dissection arise in what part of the aorta?
ascending aorta
Classify aortic dissection according to DeBakey
Type A: proximal lesion involving with both the ascending and descending aorta (types I) or just the ascending aorta (Type II)
Type B: arise after the branching of the great vessels, usually beginning distal to the subclavian artery (also called Type III).
the most common cause of death of aortic dissection include:
rupture into pericardial, pleural, or peritoneal cavities.
What are some common clinical manifestations of aortic dissection?
- cardiac temponade and aortic insufficiency
- extension into great arteries of the neck, or into the coronary, renal, mesenteric, or iliac arteries, causing vascular obstruction and ischemic consequences such as MI, involvement of spinal arteries causing transverse myelitis
How is Type A aortic dissection usually treated? Type B?
Type A: aggressive antihypertensive coupled with surgical plication of aortic intimal tear.
Type B: conservatively; either with surgery or antihypertensive meds only
The clinical manifestations of vasculitis include:
constitution signs and symptoms like fever, myalgias, arthralgias, and malaise. Specific signs and symptoms are referable to the specific tissues involved.
The two common pathogenic mechanisms of vasculitis are immune-mediated inflammation and direct invasion of vascular walls by infectious pathogens. Why is it important to make that distinction?
Immunosuppressive therapy is appropriate for immune-mediated vasculitis but could very well be counter-productive for infectious vasculitides.
immunologic injury in noninfectious vasculitis may be caused by what four general ways
- Immune complex deposition
- Antineutrophil cytoplasmic antibodies
- Antiendothelial cell antibodies
- autoreactive T cells
Immune complex vasculitis is implicated in what systemic conditions?
- SLE,
2. drug hypersensitivity, 3. secondary to exposure to infectious agent.
How does drug hypersensitivity vasculitis commonly present?
Skin lesions are most common.
_ is a neutrophil azurophilic granule constituent that shares homology with many microbial peptides, and are associated with polyangiitis.
PR3-ANCA
_ is a lysosomal granule constituent involved in O2 radical generation and are induced by several therapeutic agents, particularly propylthiuracil and are associated with microscopic polyangiitis and Churg-Strauss syndrome
MPO-ANCA
Explain the plausible mechanism for ANCA vasculitis
Drugs or cross reactive microbial antigens induce ANCA formation; or leukocyte surface expression or release of PR3/MPO incites ANCA development in susceptible host. Subsequent infection, endotxoin exposure or inflammatory stimulus elicits cytokines such as TNF that upregulate the surface expression of PR3 and MPO on neutrophils and other cells.
Why is ANCA-associated vasculitides described as Pauci immune?
ANCA autoantibodies are against cellular constituents and do not form circulating immune complexes and thus these lesions do not contain demonstrable ab and complement
Giant cell arteritis is most common form of vasculitis among what age group?
Older than 50
_ is a chronic vasculitis described as chronic inflammatory disorder of a large small-size arteries that principally affects arteries in the head.
Giant cell arteritis.
Giant cell arteritis stems from _ cell mediated immune response against one of handful of vessel wall antigen that drives subsequent proinflammatory cytokine production particularly TNF
T cell
describe the clinical features of giant cell arteritis
- rarely before age 50
- symptoms may be vague such as fever, fatigue, wt loss. Or may present with facial pain or headache, most intense along the course of superficial temporal artery which can be painful to palpation
- Ocular symptoms appear abruptly in about 50% of pts; ranges from diplopia to complete blindness
What features of giant cell arteritis supports that it has a cellular immune etiology
- granulomatous responses
- correlation with certain MHC class II haplotypes
- Prompt therapeutic response to steroids
How is diagnosis of giant cell arteritis confirmed?
biopsy and histology
_ is a granulomatous vasculitis of medium and larger arteries characterized mainly by ocular disturbances and marked weakening of pulses in the upper extremities (pulseless disease)
Takaysu arteritis
In many ways, Takayasu arteritis are similar to giant cell arteritis. the distinction is typically made based on what features?
Age of patients. In patients older than 50, the diagnosis is giant cell aortitis, while those younger than 50 its Takayasu
Takayasu arteritis classically involves what structures?
Classically involves the aortic arch. In 1/3 of patients the remainder of aorta and its branches with pulmonary artery involvement in half the cases; coronary and renal arteries may be similarly affected.
A 34 yr old patient presents with fatigue, recent weight loss, and fever. He also complained about changes in vision that have been getting progressively worse. On physical exam, his carotid and upper extremities pulses were noticeably weak. you suspect a type of vasculitis. What is the usual course of this disease?
(Patient has Takayasu arteritis) Disease course is variable. In some rapid progression, while others enter a quiescent stage after 1 to 2 years permitting long term survival albeit with visual or neurologic deficits.
Polyarteritis nodosa (PAN) typically involves what type of arteries and spares which ones?
involves small or medium sized muscular arteries, typically renal and visceral vessels but spares pulmonary circulation.
A patient presents with a fever, diffuse myalgias, abdominal pain, a peripheral neuropathy, as well as hypertension and a recent weight loss of 10 pounds. The patient has a past medical history of hepatitis B and C and is seropositive for HBsAg. Angiography demonstrates a “string of pearls appearance” in the renal artery, as well as in several other organ systems with the exception of the pulmonary arteries.
A. what is the diagnosis?
B. What therapy is usually effective?
C. what age group does it commonly affect?
D. Histologically what are characteristic findings?
E. What kind of necrosis is seen in vessel wall?
F. The inflamed vessel wall are susceptible to what complication?
G. Classic presentation include
A. Polyarteritis Nodosa (PAN)
B. immunosuppressive therapy is usually effective (90% cure rate)
C. may affect any age group, but classically young adults
D. Classic PAN is characterized by segmental transmural necrotizing inflammation of small to medium sized arteries containing neutrophils, esoinophils, lymphocytes and macrophages (NOT granulomatous like you’d see in giant cell arteritis).
E. Fibrinoid necrosis
F. Thrombus formation, aneurysm, or rupture
G. rapidly accelerating HTN due to renal a involvement, abd pain, bloody stools; diffuse myalgias; peripheral neuritis, predominantly affecting motor nerves
A 4-year-old male presents with conjunctival injection and a rash that has persisted for quite some time. On physical exam the patient has a bright red tongue, adenopathy, and hepatosplenomegaly as well as a fever that has persisted for the past 7 days. Pt was treated with IV immunoglobulin and recovered.
A. what is the diagnosis?
B. What is the typical age group involved?
C. What sized vessels are typically involved?
D. Greatest risk for these patient is involvement of what?
E. Vascular damage is primarily mediated by activation of what cells
F. What is the typical presentation?
G. What’s the treatment?
A. Kawasaki disease
B. Illness of infancy and childhood (80% of patients are 4 or younger);
C. Arteritis affecting large to medium-sized, and even small vessels.
D. Clinical significance stems primarily from a predilection for coronary artery involvement that can cause aneurysms that rupture or thrombose, resulting in acute MI.
E. Vascular damage is primarily mediated by activated T cells and monocytes/macrophages
F. Typical presentation can be remembered by: Crash and burn: CRASH stands for: conjunctivitis, Rash, Adenopathy, Strawberry tongue, Hepatosplenomegaly. Burn represents fever.
G. usually self limited but IV immunoglobulin and aspirin are indicated to lower the risk of a coronary event
_ is a necrotizing vasculitis that generally affects capillaries, as well as small arterioles and venules.
Microscopic polyangiitis. Also called hypersensitivity vasculitis or leukocytoclastic vasculitis.
How are the lesions seen in microscopic polyangiitis distinguished from those of polyarteritis nodosa?
All lesions of microscopic polyangiitis tend to be of the same age in any given patient and are distributed more widely.
90% of patients with microscopic polyangiitis develops what renal disease?
necrotizing glomerulonephritis
What vessels are usually involved in microscopic polyangiitis?
The skin, mucous membrane, lungs, brain, heart, GI, kidneys and muscle can all be involved. kidney and lungs are particularly common.
How does microscopic polyangiitis look histologically?
Segmental necrotizing inflammation with fibrinoid necrosis. Leukocytoclastic vasculitis is the classic term associated with it.
Microscopic polyangiitis has an association with which antineutrophil cytoplasmic antibodyies?
MPO-ANCA
The classic presentation of microscopic polyangiitis involves _
depends on the vascular bed involved, but major clinical features are hemoptysis, hematuria and proteinuria, bowel pain or bleeding, muscle pain or weakness, and palpable cutaneous purpura.
Pts with microscopic polyangiitis, except for those in whom widespread renal or brain involvement develop, what therapy induces remission and markedly improves long term survival?
Immunosuppressive therapy
A 21-year-old Caucasian male presents to your office with wheezing and rhinitis. Laboratory results show peripheral eosinophilia and antibodies against neutrophil myeloperoxidase.
A. What is the most likely diagnosis, provide a brief definition.
B. what vessels (size and location) are typically involved?
C. Almost half of the deaths in these patients are due to _
D. This disease usually resembles PAN or m.Polyangiitis with the addition of what two charcterisitics?
E. Which ANCA positivity is usually seen?
A. Churg-Strauss syndrome, aka Eosinophilic granulomatosis with polyangiitis, aka allergic granulomatosis and angiitis. Commonly defined as a syndrome of small-vessel necrotizing vasculitis classically associated with asthma, allergic rhinitis, lung infiltrates, peripheral hyperesoinophilia, and extravascular necrotizing granulomata.
B. Small vessels
C. Heart involvement leading to cardiomyopathy from eosinophilic infiltrates.
D. Granulomas and eosinophils
E. Mostly MPO-ANCAs
A 21 year old college student presents to the university clinic concerned that he might have contacted an STI from a one-night-stand a couple of weeks ago. He has painful ulcerative lesions on his penis and oral mucosa. The only inconsistent finding with this presentation is a mild arthritis. Pt states this is not the first time he has had something like this. Upon further workup and proper diagnosis, doc treated him with TNF-antagonist therapy and patient recovered fully.
A. what is the likely diagnosis?
B. What classic triad of symptoms are associated with this disease
C. What HLA haplotype has an association with this disease?
D. What geographic location is it mainly found?
E. Aneusrysm formation is a risk factor if it involves _
F. Treatment?
A. Behcet disease: small to medium vessel neutrophilic vasculitis
B. Classically presents as a clinical triad of recurrent oral aphthous ulcers, genital ulcers, and uveitis.
C. HLA-B51
D. Eastern mediterranean and Fast East.
E. Visceral organ systems.
F. Immunosuppression with steroids or TNF-antagonists
A 62-year-old Caucasian male presents to your office with hemoptysis and hematuria. On physical exam you note a saddle nose deformity. Laboratory results show an elevated level of cytoplasmic antineutrophil cytoplasmic antibody.
A. what is the likely diagnosis?
B. what ANCA are you likely to see on serology?
C. THis disease is a necrotizing vasculitis characterized by a triad of:
D. If it’s limited, what signs are usually present? Diffuse?
E. What immune cell mediates the hypersensitivity?
F. How do the lesion appear histologically?
G. What gender is more?
H. What are some classic features:
I. How is this disease distinguished from PAN?
J. What’s the usual treatment?
A. Granulomatosis with polyangiitis, previsouly called Wegner granulomatosis.
B. PR3-ANCA
C. 1) necrotizing granulomas of the upper respiratory tract or lower respiratory tract, or both; 2) Necrotizing or graulomatous vasculitis affecting small to medium sized vessel mostly in the lungs and upper airways; 3) Focal necrotizing, often crescentic glomerulonephritis
D. Limited form is restricted to respiratory tact. Widespread can affect eyes, skin, other organs notably the heart.
E. T cells
F. granulomas with geographic patterns of central necrosis and accompanying vasculitis. In the glomeruli you’ll see focal and segmental necrotizing glomerulonephritis.
G. Male, average age of 40
H. Persistent pneumonitis with bilateral nodular and cavitary infiltrates, chronic sinusitis, mucosal ulceration of the nasopharynx, and evidence of renal disease
I. clinically resembles PAN except that there is also respiratory involvement
J. Immunosuppressive therapy is usually successful. Untreated 80% mortality in one year.
An 31-year-old Israeli male with a history of heavy smoking presents to your office with painful ulcerations on his hands and feet. Upon examination, he is found to have hypersensitivity to intradermally injected tobacco extract.
A. What is the likely diagnosis? What is this disease usually defined/characterized as?
B. Which arteries are usually involved?
C. Histologically how do the lesions appear?
D. what is the clinical manifestation?
A. Thromboangiitis obliterans aka Buerger Disease. Characterized by segmental, thrombosing, acute and chronic inflammation of medium-sized and small arteries, mainly tibial and radial arteries with occasional secondary extension into the veins and nerves of extremities.
B. Medium sized and small arteries
C. Focal acute and chronic vasculitis with small microabsesses compound of neutrophils surrounded by granulomatous inflammation
D. cold-induced Raynaud phenomenon, leg pain, instep foot pain indued by exercise, and superficial nudular phebitis. Vascular insufficiency can eventually lead to frank gangrene.
Vasculitis resmbling hypersensitivity angiitis or classic polyarteritis nodosa can sometimes be associated with what other disorders?
- Rheumtoid arthritis,
- systemic lupus erythematosus,
- Malignancy
- systemic illness such as cryoglobulinemia, antiphospholipid ab syndrome; Henoch schonnlein purpura.
Infectious vasculitis is usually caused by what bacteria/fungi and what is the most significant complication?
Bacteria: pseudomonas; fungi: aspergillus and Mucor species.
can weaken arterial walls and culminate in mycotic aneurysm or induce thrombosis and infarction.
_ results from exaggerated vasoconstriction of arteries and arterioles in extremities, particularly fingers, toes, nose, earlobes, lips; and can induce paroxysmal pallor and cyanosis in severe cases.
Raynaud phenomenon
In Raynaud phenomenon, how do the digits classically present?
red, white, blue color changes from most proximal to most distal, correlating with proximal vasodilation, central vasoconstriction, and more distal cyanosis.
Distinguish between primary and secondary raynaud phenomenon.
Primary: exaggerated central and local vasomotor responses to cold or emotion; predilection for young women. Usually symmetric involvement of extremities. usually benign
Secondary: refers to vascular insufficiency due to arterial disease cuased by other entities like SLE, scleroderma, Buerger disease or atherosclerosis. Usually has asymmetric involvement of extremities. Worsens with tiime.
A 48-year-old male presents to his primary physician with the chief complaints of fever, abdominal pain, weight loss, muscle weakness, and numbness in his lower extremities. UA is normal. A biopsy of the sural nerve reveals transmural inflammation and fibrinoid necrosis of small and medium arteries. Chart review reveals a remote history of cigarette smoking as a teenager and Hepatitis B seropositivity. What is the most likely diagnosis?
PAN
Cardiac Raynaud is characterized by _
excessive vasoconstriction of myocardial arteries or arterioles that may cause ischemia or infarct.
What endogenous/exogenous agents can lead to myocardial vessel vasopasm?
Endogenous: epinephrine from pheochromocytoma or elevated thyroid hormone; Exogenous: cocaine or phenylephrine.
How does myocardial vessel vasospasm present hisotologially?
contraction band necrosis: microscopic areas of necrosis characterized by myocyte hypercontraction
Takotsubo cardiomyopathy is associated with which vascular hyperreactivity disorder?
Myocardial vessel vasospasm. Takotsubo cardiomyopathy is also known as broken heart disease cuz of it’s assocation with emotional duress.
Varicose veins are abnormal dilation of veins with valvular incompetence secondary to _
sustained intraluminal pressure as seen in stasis, congestion, thrombus, edema, and ischemia of overlying skin (stasis dermatitis “browny induration”)
Esophageal varices is mainly due to 1. Clinical significance arise from possibility of 2.
- portal hypertension (often due to cirrhosis) opens portosystemic shunts which direct blood to veins at the gastroesophageal junction.
- rupture
Hemorrhoids is dilation of the venous plexus at the 1.
anorectal junction. may cause pain, bleeding and ulcerate.
The single most important risk factor for developing a DVT in the LE is 1 and other risk factors include_2_
- prolonged inactivity/immobilization.
2. systemic hypercoagulability such as includes Factor V leign, polycythemia vera, cancer paraneoplastic syndrome.
The most serious potential consequence of DVT is
pulmonary embolism
What is Trousseau sign?
migratory thrombophelebitis where thromboses classically appear in one location, disappear, and then occur in another site. Associated with hypercoagulability states as seen as a result of paraneoplastic syndrome. Particularly seen with mucin-producing adenocarcinomas like lung, ovary , and pancreas.
Superior vena cava syndrome is usually caused by_1_ and clinical characteristic include 2.
- neoplasm that compress or invade the superior vena cava, such as bronchogenic carcinoma or mediastinal lymphoma.
- dilation of the veins of head, neck, and arms with cyanosis. pulmonary vessels can also be compressed and cause respiratory distress.
Inferior vena cava synndrome can be caused by 1 and clinically characterized by 2.
- neoplasm that compress or invade the IVC or by thrombosis of the hepatic, renal or lower extremity veins that propagates cephalad.
- Marked lower extremity edema, distention of superficial collateral veins of the lower abdomen with renal vein involvement –> massive proteinuria
Lymphangitis is commonly caused by _1 and vessels are filled with _2. Clinically presents as 3.
group A beta hemolytic streptococi.
- exudate of neutrophils and monocytes; and can produce cellulitis or focal absecsses.
- red, painful subcutaneous steaks andpainful enlargement of the draining lymph nodes.
Primary lymphedema is usually caused by _
isolated congenital defect of as familal Milroy disease which result in lymphatic agenesis of hypoplasia.
Secondary lymphedema is usually cuased by _
aka obstructive lymphedema, stems from blockage of a previously normal lymphatic due to malignant tumors, surgical procedures, post-irradiation fibrosis filariasis, postinflammatory thrombosis and scarring.
peau d’organge is due to _
persistent edema and subsequent deposition of interstitial connective tissue
Hemangiomas are characerized by_ and common sites include _.
localized increase in neoplastic blood vessels. Common sites include skin, mucous membranes of head and neck and in liver
This type of benign tumor is very common and accounts for 7% of all benign pediatric tumors.
Hemangiomas
Name 3 types of hemangiomas
- Capillary hemangiomas
- Cavernous hemangiomas
- Pyogenic granulomas
The most common type of vascular tumor, occurring primarily in skin or mucous membanes
Capillary hemangiomas
_ is a variant hemangioma is present at birth, grows rapidly for a few months, regresses and is usually gone by age 7
Juvenile (strawberry) hemangioma
This unencapsulated lesion is usually 1mm to several cm in size, is composed of closely packed aggregates of capillary-sized, thin walled vessels.
capillary hemangioma
These unencapsulated lesions are usually 1 to 2 cm in diameter, and exhibit large thin-walled vascular spaces. The skin and liver are a common site with lesions also occurring in the CNS. These do not regress and can be locally destructive. Associated with von Hippel-Lindau disease.
Cavernous hemangiomas
These are an ulcerated polypoid variant of capillary hemangioma, often following trauma; they resemble exuberant granulation tissue. They can also occur in pregnant women.
Pyogenic granuloma
this pregnancy tumor is essentially a pyogenic granuloma
Granuloma gravidarum
These are the analog to cavernous hemangioma, occurring in children in the neck or axilla; can sometimes be large ( up to 15 cm) and produce gross deformities. They are not well encapsulated and complete surgical resection can be difficult.
Cavernous lymphangiomas (cystic hygromas)
What is a glomus body?
component of the dermis layer of the skin, involved in body temperature regulation. The glomus body consists of an arteriovenous shunt surrounded by a capsule of connective tissue. Glomus bodies are most numerous in the fingers and toes.
_ is a benign, exquisitely painful tumor of modified smooth muscle cells arising from the glomas body; these tumor most commonly occur in the distal phalanges, especially beneath nail beds. Excision is curative.
Glomus tumor/glomangioma
Name 3 vascular ectasias
- Nevus flammus
- spider telangiectasias
- Hereditary hemorrhagic telangiectasia (HHT), also known as Osler–Weber–Rendu disease and Osler–Weber–Rendu syndrome, is an autosomal dominant genetic disorder that leads to abnormal blood vessel formation in the skin, mucous membranes, and often in organs such as the lungs, liver, and brain
- telangiectasias: a condition characterized by dilation of the capillaries, which causes them to appear as small red or purple clusters, often spidery in appearance, on the skin or the surface of an organ.
A variant of nevus flammeus (birthmarks) and tend to grow along with the child, and thickening the involved skin
Port wine stain
Port-wine stains (a variant of nevus flammeus), leptomeningeal angiomatous masses, mental retardation, seizures, hemiplegia and skull radiopacities compose this syndrome.
Sturge-Weber syndrome
These are minute subcutaneous arterioles often pulsatile, arranged in radial fashion around a central core. They typically occur above the waist and are associated with hyperestrogenic states.
Spider telangiectasias
Hereditary hemorrhagic telengiectasia is also known as what disease?
Osler-weber-rendu disease
This rare autosomal dominant disease is characterized by multiple small (<5mm) aneurysmal telangiectasias on skin and mucous membranes. Patients present with epistaxis, hemoptysis, or gastrointestinal or genitourinary bleeding.
Hereditary hemorrhagic telengiectasia/Olser-Weber-Rendu disease
This is a vascular proliferation resulting from opportunistic infection in an immunocompromised host; lesions can involve the skin, bone, brain and other organs. It is caused by a gram-negative bacillus of the Bartonella family.
Bacillary angiomatosis. Commonly bartonella
A patient presents with multiple red papules and nodular subcutaneous masses. microscopically there are capillary proliferations composed of atypical endothelial cells admixed with neutrophils, nuclear dusts and bacteria. Treatment with erythromycin is curative.
Bacillary angiomatosis
List 4 tumors and tumor-like lesion of the vessels
- Hemangiomas
- Lymphangiomas
- Glomus tumor/glomangiomas
- Bacillary angiomatosis
List two intermediate-grade tumors of the vasculature
Kaposi sarcoma
Hemangioendothelioma
Kaposi sarcoma is categorized into 4 varieties; all of which share the same underlying viral pathogenesis:
- Chronic/classic/european kaposi sarcoma
- Lymphadenopathic/African/endemic kaposi sarcoma
- Transplant-associated kaposi sarcoma
- Acquired immunodefiency syndrome (AIDS)-associated (epidemic) kaposi sarcoma
This type of kaposi sarcoma occurs typically in elderly men of eastern european (ashkenazi jew) or mediterranean descent. Lesions are red-purple cutaneous plaques and nodules on the lower extremities. Is not associated with HIV
Chronic/classic/european kaposi sarcoma
This type of kaposi sarcoma has the same distribution of Burkkit lymphoma and is not associated with HIV. It occurs largely in lymph nodes rarely with aggressive visceral involvement.
Lymphadenopathic/African/endemic kaposi sarcoma
This type of kaposi sarcoma occurs in patients receiving chronic immunosuppression. Nodal, mucosal, and visceral involvement can be aggressive (and fatal). Lesions may regress when immunosuppression is discontinued.
Transplant-associated kaposi sarcoma
This type of kaposi sarcoma may occur anywhere in the skin and mucous membranes, lymph nodes, gastrointestinal tract, or viscera. wide dissemination occurs early. This type is associated with HIV.
Acquired immunodefiency syndrome (AIDS)-associated (epidemic) kaposi sarcoma
More than 95% of kaposi sarcoma lesions are infected with this virus.
HHV8
What are the 3 stages of kaposi sarcoma lesions?
Patches - pink purple papules
Raised plaques
Nodular lesions - distinctly neoplastic and often involve lymph nodes
This type of neoplasm has a clinical behavior that straddles benign and malignant. The epithelioid type is most often cured by excision, although 40% recur, 20% metastasize and 15% of patients die.
Hemangioendothelioma
Name 2 malignant tumors of blood vessels.
Angiosarcoma
Hemangiopericytoma
This malignant endothelial neoplasm can occur anywhere, but tend to arise in the skin, soft tissue, breast and liver. They are aggressive, metastasize quickly give the patient a 5 year survival rate of 30%.
Angiosarcoma
This type of angiosarcoma is associated with exposure to arsenic, polyvinyl chloride and Thorotrast.
Hepatic angiosarcoma
This type of malignant tumor can develop in long-term chronic lymphedema; classically in the ipsilateral arm years after radical mastectomy. It arises from dilated lymphatic vessels.
lymphangiosarcoma
Large cavernous lymphangiomas of the neck are often seen in what genetic disorder?
Turner syndrome
Warthin- Starry stain can be used to visualize this tumor-like lesion.
Bacillary angiomatosis
