Neo Blood Vessels- Phase 4 Flashcards
ReKap
Drugs used to treat chronic hypertension in pregnant women include methyldopa, labetalol, nifedipine, and hydralazine (for severe hypertension).
Methyldopa is converted to α-methylnorepinephrine, which is an alpha-2-adrenergic receptor agonist.
ACE inhibitors, angiotensin receptor antagonists, and aldosterone receptor antagonists are teratogenic and therefore contraindicated in pregnant women.
Analysis
The correct answer is E. Pregnant women with chronic hypertension are thought to require antihypertensive therapy when the diastolic pressure is greater than 100 mm Hg. However, some clinicians may decide to treat patients with diastolic blood pressures of less than 100 mm Hg. For initiation of therapy, methyldopa is the drug of choice. Methyldopa is converted intraneuronally to α-methylnorepinephrine, an alpha-2-adrenergic agonist. Release of α-methylnorepinephrine in the medulla leads to a decrease in sympathetic outflow, which decreases blood pressure. Methyldopa has been safely used in the treatment of hypertension during pregnancy; this agent is not associated with the development of teratogenic or other fetal abnormalities.
The antihypertensive medications most commonly used in pregnancy are methyldopa, labetalol, nifedipine, and hydralazine (for severe hypertension). It should be noted that gestational hypertension is different from preeclampsia in that preeclampsia is also associated with proteinuria and generally occurs after 20 weeks’ gestation. The same antihypertensives are used for preeclampsia as in gestational hypertension, and magnesium sulfate can be added if the patient is experiencing seizures (eclampsia).
Spironolactone antagonizes aldosterone receptors in the distal segments, including the collecting duct (choice A). This potassium-sparing diuretic should not be administered to pregnant women (pregnancy category C) because it readily crosses the placental barrier and possesses antiandrogenic activity, which may adversely affect sex differentiation of the male during embryogenesis.
Angiotensin II receptor antagonists (choice B; e.g., candesartan, losartan, and valsartan) and angiotensin-converting enzyme (ACE) inhibitors (e.g., captopril, enalapril, and ramipril), which act by inhibiting the conversion of angiotensin I to angiotensin II (choice D), should not be administered to pregnant women (pregnancy category D). The use of these agents during the second and third trimesters is contraindicated because they have been associated with severe fetal and neonatal injury, hypotension, neonatal skull hypoplasia, anuria, renal failure, and death.
Loop diuretics act by inhibiting sodium and chloride reabsorption in the loop of Henle (choice C). The loop diuretics are often avoided because these agents can produce hypovolemia, leading to reduced uterine blood flow. These drugs do not have teratogenic effects.
ReKap
Starling equation: net filtration pressure = (Pc– PIF) – (πc–πIF), also often rearranged as (Pc + πIF) - (PIF + πc).
Pc = capillary hydrostatic pressure; PIF = interstitial fluid hydrostatic pressure; πc = capillary colloid osmotic pressure; πIF = interstitial fluid colloid osmotic pressure.
Edema is caused by abnormally increased net filtration pressure.
Analysis
The correct answer is E. Use the Starling equation to calculate the direction and net filtration pressure for fluid movement [net filtration pressure = (Pc– PIF) – (πc – πIF)].
The figure shows the forces that determine fluid movement.
Pc = capillary hydrostatic pressure = 12 mm Hg
πc = capillary colloid osmotic pressure = 12 mm Hg
PIF = interstitial fluid hydrostatic pressure = 2 mm Hg
πIF = interstitial fluid osmotic pressure = 4 mm Hg
Substituting these values into the equation and solving for the net filtration pressure, we get:
Net filtration pressure = (12 – 2) – (12 – 4) mm Hg
Net filtration pressure = 10 – 8 = +2 mm Hg
The net filtration pressure, in this case, is positive, which means that fluid is being forced out of the capillary.
It is also important to understand the Starling equation on a conceptual level to avoid rote memorization. Hydrostatic pressure results from gravitational/fluid pressure, and osmotic pressure arises from the tendency of fluid to move towards more concentrated solutions. Think of hydrostatic pressure as a “pushing” force and plasma protein osmotic pressure as a “pulling” force.
Thus, the outward forces driving fluid filtration across the capillary wall into the interstitium include capillary hydrostatic pressure (+12 mm Hg) and interstitial fluid colloid osmotic pressure (+4), which yield a total outward filtration pressure of +16 mm Hg. Inward forces driving fluid back into the vasculature include capillary colloid osmotic pressure (+12 mm Hg) and interstitial fluid hydrostatic pressure (+2), which yield a total inward directed pressure of +14 mm Hg. Overall, the net filtration pressure can then be calculated as outward pressure (+16 mm Hg) minus inward pressure (+14 mm Hg) = +2 mm Hg.
In edematous states, there is elevated net filtration pressure, resulting in an accumulation of interstitial fluid. Causes include congestive heart failure (due to elevated capillary hydrostatic pressure, increased “pushing” force), decreased plasma albumin (due to reduced capillary osmotic pressure, decreased “pulling” force), and impaired lymphatic function (due to increased interstitial colloid osmotic pressure).
ReKap
In adult-type coarctation of the aorta (postductal), look for:
Hypertension in the upper extremities secondary to decreased blood flow to the kidneys and RAAS activation.
Hypotension in the lower extremities due to decreased perfusion, often presenting with claudication.
Rib notching due to increased collateral circulation.
Hypertension occurs secondary to decreased blood flow to the kidneys and RAAS activation.
Analysis
The correct answer is B. The patient presents with the adult form of coarctation of the aorta, caused by stenosis in the aortic arch just distal to the left subclavian artery (postductal).
Coarctation creates a resistance to flow that leads to hypertension proximal to the obstruction and hypotension distal to the stenotic segment.
Collateral arteries (e.g., the intercostal and internal mammary arteries) enlarge and establish communication between aortic segments proximal and distal to stenosis.
Enlarged intercostal arteries cause notching of the inferior margins of the ribs, which is diagnostic.
Hypertension in the upper part of the body manifests with headache, dizziness, and other neurologic symptoms.
Hypertension is due to decreased renal blood flow activating the renin-angiotensin-aldosterone system (RAAS).
Hypotension in the lower part of the body results in signs and symptoms of ischemia, most often claudication, i.e., recurrent pain due to ischemia of leg muscles.
Remember that the infantile form of aortic coarctation is associated with patent ductus arteriosus, whereas the adult form is not.
The image below shows coarctation of the aorta: (A) Preductal; (B) Postductal; (C) Collateral circulation.
Aortic valvular stenosis (choice A) at this age would most likely be caused by a congenitally malformed valve, usually a valve with two cusps or a single cusp. Aortic stenosis manifests with systolic hypotension, recurrent syncope, and hypertrophy/dilatation of the left ventricle. Low systolic pressure is present in the entire body.
The isolated form of patent ductus arteriosus (choice C) leads to the shunting of blood from the aorta to the pulmonary artery. Eventually, chronic cor pulmonale develops with resultant right-sided heart failure. Patent ductus arteriosus would not cause a pressure difference between the upper and lower body.
Pulmonary valvular stenosis (choice D) is a rare form of congenital heart disease that leads to chronic cor pulmonale and heart failure.
Vasculitis involving the aortic arch (choice E) is found in Takayasu arteritis, in which chronic inflammatory changes develop in the aortic arch and its branches (brachiocephalic trunk, left common carotid, and left subclavian arteries). This condition affects women primarily (80–90% of cases). Arteritis causes arterial stenosis, presenting with signs and symptoms of ischemia to the brain, eye, and the upper part of the body. Because the radial pulses are very weak or absent, this disorder is also known as “pulseless disease.”
Updated on 11/21/20
ReKap
Thromboangiitis obliterans (Buerger disease):
Idiopathic segmental thrombosing vasculitis of small and medium-sized peripheral arteries/veins
Usually associated with claudication, superficial nodular phlebitis, paresthesia, Raynaud phenomenon, and heavy smoking history in male patients <40 years of age
Complications include limb gangrene, ulcerations, and autoamputation of digits
Smoking cessation can reduce disease progression
Analysis
The correct answer is E. Thromboangiitis obliterans (Buerger disease) is an idiopathic segmental thrombosing vasculitis of small and medium-sized peripheral arteries in the upper and lower extremities. It is most commonly seen in male patients <40 years of age who are heavy smokers. Chronic vasculitis can lead to the extension of arterial inflammation to contiguous peripheral veins and nerves and possible encasement of these structures with connective tissue due to systemic fibrosis.
Thromboangiitis obliterans generally presents with claudication, which improves but does not completely resolve with rest, along with superficial nodular phlebitis, paresthesias (due to nerve involvement), and Raynaud phenomenon (blue discoloration of skin upon exposure to cold temperatures). The most severe complications of this condition include limb gangrene, ulcerations, and autoamputation of digits. Intradermal injection of tobacco extracts in patients with thromboangiitis obliterans will often demonstrate a local hypersensitivity reaction. The main treatment for thromboangiitis obliterans is smoking cessation, which often reduces the progression of vasculitis.
Abnormal electrolytes (choice A), specifically hypocalcemia, hypokalemia, and hypomagnesemia, can cause lower extremity pain and cramping with exertion. This patient’s laboratory studies are within normal limits. Electrolyte abnormalities are not associated with the Raynaud phenomenon. Smoking cessation would not be the most appropriate treatment.
Atherosclerosis (choice B) may be present in heavy smokers, as smoking is an independent risk factor for atherosclerosis and peripheral vascular disease. These conditions are less likely in patients <40 years of age. Atherosclerotic disease usually involves large vessels and is characterized by less severe pain that resolves completely at rest. Atherosclerosis is also not associated with the Raynaud phenomenon.
Autoimmune diseases (choice C) such as rheumatoid arthritis, systemic lupus erythematosus (SLE), and Sjögren syndrome are associated with vasculitis in some cases. Thromboangiitis obliterans is not an autoimmune condition. This patient’s young age (<40 years old), male gender, heavy smoking history, severe claudication, and Raynaud phenomenon makes thromboangiitis obliterans a much more likely diagnosis. Autoimmune diseases usually require treatment with immunosuppressant drugs.
Nerve compression (choice D) due to conditions such as sciatica or spinal stenosis is characterized by a sharp, radiating (neuropathic) pain in the lower extremities. Nerve compression in lumbar spinal stenosis can lead to neurogenic claudication (also known as pseudoclaudication), where lower extremity pain is made worse by standing or walking and is usually relieved by sitting or lying down. It is not associated with heavy smoking or Raynaud phenomenon.
ReKap
Temporal arteritis should be suspected in a woman over 50 years old with a headache, muscle aches, jaw claudication, tenderness of the temples, and an elevated erythrocyte sedimentation rate (ESR).
Biopsy of the temporal artery shows granulomatous lesions with giant cells.
If left untreated, temporal arteritis can progress to blindness.
Analysis
The correct answer is C. This patient likely presents with a diagnosis of temporal (giant cell) arteritis. The most feared complication of this disease is blindness due to the involvement of the ophthalmic artery and posterior ciliary arteries.
Temporal arteritis:
Panarteritis involving large vessels, including branches of the aortic arch and the carotid system
Disease classically involves the superficial temporal artery (branch of the external carotid)
Biopsy of involved arteries shows granulomatous lesions with giant cells and inflammatory infiltrates
Temporal arteritis usually female patients over 50 years old
Elevated erythrocyte sedimentation rate (ESR)
Symptoms include new headache, jaw claudication (due to inflammation of arteries supplying muscles of mastication), polymyalgia rheumatica (stiffness and aching in proximal muscles without weakness or creatine kinase elevation), and systemic symptoms including fever, fatigue, and weight loss
Patients may also develop ascending aortic aneurysms and have slightly decreased hematocrit due to anemia of chronic disease
The risk of blindness means that the threshold for diagnosis is low, and you should be suspicious of temporal arteritis in any patient over 50 with new headaches and an elevated ESR. Glucocorticoid therapy is started immediately even without tissue diagnosis when temporal arteritis is suspected in order to prevent potential blindness. Biopsies of the temporal artery can be performed to confirm the diagnosis.
Aphasia (choice A) might conceivably result from a stroke affecting the inferior frontal gyrus or from a lesion of the brainstem centers controlling phonation, but visual disturbances are more common in temporal arteritis than stroke.
Arthritis (choice B) is not classically associated with temporal arteritis. However, many other systemic inflammatory conditions can produce arthritis including psoriasis, ankylosing spondylitis, and inflammatory bowel disease. Pain with chewing and unilateral headaches would not be typical symptoms of these diseases.
Isolated deafness (choice D) is not commonly seen with temporal arteritis.
Paralysis (choice E) is not a common complication of temporal arteritis.
ReKap
Patent ductus arteriosus (PDA) is a persistent direct communication between the aorta and pulmonary artery after birth. The ductus arteriosus is normally patent in fetal circulation and closes shortly after birth.
PDA is characterized by a continuous “machinery” murmur on auscultation and is associated with maternal rubella infection.
If the lesion is not corrected or the ductus is widely patent, pulmonary hypertension may develop and the left-to-right shunt may reverse (Eisenmenger syndrome).
Analysis
The correct answer is D. Our patient presents with a continuous, “machinery-like” murmur on auscultation, which is consistent with a diagnosis of patent ductus arteriosus (PDA). The ductus arteriosus is a normal part of fetal circulation that allows blood to be diverted from pulmonary vasculature directly to the aorta. Soon after birth, the ductus closes due to an increase in oxygen saturation and reduction in circulating prostaglandins.
Fetal circulation and oxygenation pathway. Ductus arteriosus normally shunts deoxygenated blood away from the fetal lungs, which are not functional in-utero.
In some patients, the ductus arteriosus fails to close, resulting in a PDA and postnatal shunting of blood from the aorta to the pulmonary arteries (see figure below). Initially, this may produce left-sided ventricular dilation due to persistently increased preload, causing failure to thrive due to increased cardiac metabolic expenditure. If the ductus remains widely patent for years, pulmonary hypertension may develop, reversing the left to right shunt, sending deoxygenated blood through the descending aorta and producing cyanosis (Eisenmenger syndrome). Since the deoxygenated blood enters the descending aorta, the toes can be cyanotic but the fingers are generally not. Other physical exam findings include widened pulse pressure and bounding pulses (also seen in aortic regurgitation).
Risk factors for PDA include prematurity, birth at high altitude, and maternal rubella infection. A PDA may be iatrogenically created, by treating the infant with prostaglandins (PGE), in some cases of complex congenital heart disease that require a shunt for viability. Closure of a PDA can be achieved surgically or medically using the NSAID indomethacin.
Anatomical comparison of ligamentum arteriosum (obliterated ductus arteriosus) and PDA.
An absent thymus (choice A) and hypocalcemia (choice B) are associated with DiGeorge syndrome, which results from abnormalities in the third and fourth branchial pouches that give rise to the thymus and parathyroid, respectively. The most common cardiac anomalies in these patients include tetralogy of Fallot, persistent truncus arteriosus, interrupted aortic arch, and septal defects. The first three of these conditions produce cyanosis at birth; PDA produces cyanosis later in life with Eisenmenger syndrome. Tetralogy of Fallot is often described as “boot-shaped” on chest x-ray and produces the harsh murmur of pulmonic stenosis.
Maternal diabetes (choice C) is classically associated with transposition of the great vessels, another cyanotic heart disease. Murmurs are not a prominent feature of this condition, though chest x-ray may show an “egg on a string” heart appearance.
A single palmar crease (choice E), is classically found in trisomy 21 (Down syndrome) patients. Apart from intellectual disability, characteristic facial features, and duodenal atresia, these infants can also present with endocardial cushion defects due to failure of neural crest migration. AV valve regurgitation and atrial septal defects (ASD) are more common in these patients.
ReKap
Direct renin inhibitors decrease the conversion of angiotensinogen to angiotensin I.
The resulting decrease in angiotensin II formation leads to decreased aldosterone secretion, which in turn decreases renal sodium reabsorption and potassium excretion, resulting in hyperkalemia.
Renin would increase because of the reduction in systolic blood pressure caused by the loss of aldosterones sodium and fluid conserving effects on the nephron.
Analysis
The correct answer is D. Renin is the first component of the renin-angiotensin-aldosterone system (RAAS)s various components and actions are as follows:
Renin — A protease that is released from renal juxtaglomerular cells located in the wall of the glomerular afferent arteriole following a drop in renal perfusion pressure.
Angiotensinogen — An α-globulin that is a normal plasma protein constituent. It serves as a substrate for renin.
Angiotensin I — A decapeptide released from angiotensinogen by renin.
Angiotensin-converting enzyme (ACE) — An enzyme expressed at high levels on the endothelium of pulmonary capillaries (and elsewhere).
Angiotensin II — An octapeptide released from angiotensin I by ACE. Angiotensin II is a highly potent hormonal effector:
↑ Renal Na+ and water retention
↑ Blood pressure
↑ Systemic vascular resistance
Aldosterone — A mineralocorticoid released from the adrenal cortex in response to angiotensin II (and hyperkalemia).
↑ Renal Na+ retention
↑ Renal K+ secretion
Since the investigational drug competes with angiotensinogen for renin, less angiotensin I will be formed. The following effects will occur: (1) ↑ plasma K+, ( 2) ↓ angiotensin II levels, and (3) ↑ renin.
↓ Angiotensin I → ↓ angiotensin II → ↓ aldosterone → ↓ K+ secretion → ↑ plasma K+
↓ Angiotensin I → ↓ angiotensin II
↓ Angiotensin I → ↓ angiotensin II → ↓ aldosterone → ↓ Na+ reabsorption → ↓ blood pressure → ↓ renal perfusion pressure → ↑ renin
ReKap
Resistances in parallel:
The reciprocal of the total resistance is the sum of the reciprocals of the individual resistances.
The total resistance is always less than any of the individual resistances.
Removing a resistance (complete occlusion of an organ’s vessels) increases the total resistance of the circuit.
Analysis
The correct answer is E. Decreasing the number of vessels or vascular beds in a circulation increases total vascular resistance. This question is relatively simple to answer if you know that removing a resistance from a parallel circuit increases the total resistance (RT) of that circuit.
Because only one answer choice is greater than the original resistance, it is not necessary to calculate the resistance after the removal of the organ. The total resistance with all five organs in the circuit is 0.02 mm Hg·mL·min-1. Removing an organ would produce a total resistance greater than 0.02 mm Hg·mL·min-1. 0.025 mm Hg·mL·min-1 is the only choice with a value greater than 0.02 mm Hg·mL·min-1.
Choices A, B, C, and D can be eliminated because the values of resistance are equal to or lower than the total resistance prior to the removal of the organ.
Without knowing the individual organ resistance values, a mathematical solution is not possible. The equation for parallel resistances is the following: 1/RT = 1/R1 + 1/R2 + 1/R3 + 1/R4 +1/R5. If the individual organ resistances were known, the effect of occlusion of any of the organs could be calculated.
While this relationship may not seem counter-intuitive when applied to the cardiovascular system, remember that adding a vascular bed to the circulation makes it easier for blood to escape the arterial system (i.e., there is less resistance to flow through the circulation). Remember also that when the central nervous system (CNS) shuts off flow to an organ (e.g., the skin or gut) when arterial pressure is compromised, SVR increases.
ReKap
Varicose vein formation results from chronically high venous pressure in the legs, typically due to prolonged periods of standing or other sources of venous stasis.
Analysis
The correct answer is A. This patient presents with varicose veins, which are dilated, tortuous, superficial veins with incompetent valves. Although the etiology is unclear, varicose veins can be aggravated by increased venous pressure in the legs.
Varicose Veins:
Develop with age in men and occur in association with puberty, pregnancy, and the onset of menopause in women.
Symptoms can include pain, lumpy palpable veins, skin discoloration, and ankle swelling.
Complications include poor wound healing, ulceration of the overlying skin, and venous thrombosis.
Each time a skeletal muscle contracts, blood is squeezed out of the veins within and pushed toward the heart. Valves prevent backflow. If it were not for the valves, the hydrostatic pressure effect of the column of blood from the heart to the feet would cause the pressure in the feet to be about +90 mm Hg. If a person stands perfectly still (e.g., at a cash register), the venous pump is inactive, and leg vein pressure can increase greatly.
Venous pressure may also be increased chronically during pregnancy because the fetus compresses the large veins in the abdomen. When the veins have been overstretched for long periods of time, the valves may not close properly, allowing venous pressure to escalate. A vicious cycle develops: the increase in venous pressure causes further damage to the valves, leading to increased venous pressure and greater dilatation of the vein.
Jogging (choice B) would not aggravate varicose veins. Rhythmically contracting leg muscles promotes forward venous flow reduces venous pressure in the lower extremities.
Hypertension (choice C) is usually not associated with a significant increase in venous pressure unless there is right heart failure.
Only very severe obesity (choice D) might be expected to compress the veins in the abdomen sufficiently to increase venous pressure in the legs. This is not the most direct answer.
Choice E is not even worth mentioning…
ReKap
Acute mountain sickness is caused by hypoxia resulting from reduced atmospheric O2 availability at high altitudes.
Physiologic aging is accompanied by decreased PaO2, primarily due to increasing V/Q imbalances.
At high altitudes, individuals who are older may experience O2 desaturation due to attenuated cardiopulmonary reserves.
Analysis
The correct answer is E. The grandparents are exhibiting symptoms of acute mountain sickness (AMS) caused by hypoxia. PaO2 declines linearly with age (~5 mm Hg/decade), which reduces tolerance and ability to adapt to low atmospheric O2 availability at high altitude. The PaO2 decline is primarily due to increasing ventilation-perfusion (V/Q) imbalance.
The respiratory system undergoes numerous changes with age (see Table). Fragmentation of elastic fibers in the lung parenchyma causes alveolar duct enlargement and an increased tendency to collapse during expiration, as seen in patients with emphysema. Collapse traps air, which increases residual volume (RV) and physiologic dead space. Because physiologic dead space (unlike anatomic dead space) contains a blood-gas barrier and is perfused, albeit minimally, collapse creates a V/Q mismatch and increases the alveolar-arterial (A-a) O2 gradient. V/Q mismatches usually result in a drop in PaO2.
By age 70 years, the V/Q imbalance typically has caused PaO2 at rest to have dropped from ~100 mm Hg to ~70 mm Hg. Arterial O2 saturation (SaO2) may remain relatively high (92–93%), but any challenge to the cardiopulmonary system can cause rapid desaturation and hypoxia.
The partial pressure O2 in the atmosphere decreases with increasing altitude (from 160 mm Hg at sea level to 96 mm Hg at 3,763 m). PAO2 and PaO2 in young adults fall from 100 mm Hg to ~47 mm Hg, which is at the head of the steep portion of the O2-hemoglobin dissociation curve. Arterial O2 saturation falls to 84%. The respiratory centers respond by increasing respiratory rate and cardiac output to ensure adequate O2 delivery to tissues. Adults who are older are positioned on the steep part of the O2-Hb dissociation curve, which increases susceptibility to hypoxia.
This image shows the effect on oxygen saturation in older individuals compared to younger folks at high altitudes due to higher ventilation-perfusion (V/Q) imbalance. Such an imbalance leads to decreased tolerance of low atmospheric O2 availability at these heights.
The decrease in atmospheric PO2 at altitude stimulates compensatory hyperventilation to help maintain PaO2, which leads to hypocapnia due to an increased rate of CO2 transfer to the atmosphere. AMS is not due to CO2 retention (choice A).
Chest wall compliance decreases with age (choice B) due to calcification of the cartilage and vertebral articulations, loss of chest wall muscle mass, and spinal changes. Although these changes increase the work of breathing, they do not cause the V/Q imbalances that cause PaO2 and cardiopulmonary reserve to decline with age.
Lung elastic recoil decreases with age (choice C) due to loss of elastic tissue and extracellular matrix stiffening. Although the loss of recoil limits expiratory airflow and increases work of breathing, it does not cause PaO2 to fall.
Dead space increases with age (choice D) due to premature airway collapse during expiration, but increased dead space does not, in and of itself, cause V/Q mismatching. Dead space is not ventilated (decreased V), but there is always some residual perfusion (Q) that produces the imbalance and lowers PaO2. PaO2 falls because low PO2 blood from the non-ventilated regions mixes with high PO2 blood from ventilated regions.
ReKap
Cystic hygromas contribute to the webbed neck in Turner syndrome.
Turner syndrome is associated with coarctation of the aorta (infantile type) and bicuspid aortic valve.
Analysis
The correct answer is C. This neonate has Turner syndrome with a cystic hygroma (lymphangioma), which is commonly associated with coarctation of the aorta.
Transillumination of the neck mass in this patient is characteristic of a cystic hygroma, which is a congenital lymphatic malformation. Essentially, obstruction of lymphatic drainage into the venous system results in accumulation of lymph in the fetal neck. This is a classic feature of Turner syndrome that later produces the “webbed neck” appearance in these patients. This process may also occur in the lymphatics of the hands and feet, producing lymphedema in these regions.
Other characteristic features of Turner syndrome include broad “shield” chest, high arched palate, short stature, gonadal dysgenesis (with the associated risk of developing dysgerminoma during young adulthood), hypothyroidism, and infertility.
Turner syndrome is commonly associated with two congenital heart conditions: coarctation of the aorta and bicuspid aortic valve (aortic stenosis). Coarctation of the aorta can be either infantile-type (pre-ductal), where stenosis occurs proximal to the insertion of ductus arteriosus, or adult-type (post-ductal), where stenosis occurs distal to ductus arteriosus. Turner syndrome is associated with the infantile type, which also presents with a patent ductus arteriosus (PDA). Infantile coarctation with a PDA can produce lower body cyanosis and weak pulses. This occurs because pressures distal to the coarctation are lower than pulmonary artery pressures, allowing deoxygenated blood to pass directly into the aorta through the PDA.
Other features of coarctation (seen with both types) include dizziness, headaches, syncope, weak lower extremity pulses, intermittent claudication, hypertension in upper extremities, aortic regurgitation (dilation of the aortic root), and hypoperfusion of abdominal organs. Rib notching is a radiographic finding seen with adult type (post-ductal) coarctation due to the creation of collaterals and dilation of the intercostal arteries.
The figure below shows coarctation of the aorta: (A) Preductal; (B) Postductal; (C) Collateral circulation.
Aneurysms involving the proximal aorta (choice A) suggest tertiary syphilis (syphilitic aortitis). A possible mechanism is spirochete-induced inflammation/thrombosis of the vasa vasorum supplying the wall of the proximal aorta, resulting in a weakened aortic wall that is susceptible to dilation. Clues that may point to tertiary syphilis include a history of a sexually transmitted disease or evidence of chronic neurologic signs.
Cardiac septal defects (choice B) are common conditions at birth. They can occur independently or may be related to congenital syndromes and should always be evaluated in patients with fetal alcohol syndrome, Down syndrome, and trisomy 18.
Cystic medial necrosis of the aorta (choice D) is associated with Marfan syndrome. Marfan syndrome results from a mutation in fibrillin-1, a key component of elastin, which lines arterial walls. The weakened elastic structure of the aorta causes necrosis of the media, resulting in aneurysmal and aortic dissection. Characteristic features of this disease include tall stature and hyperextensible joints.
Early severe aortic atherosclerosis (choice E) can be a feature of either diabetes mellitus (clues would include high fasting blood glucose, thirst, excessive urination, etc.) or familial hyperlipidemias (clues include xanthomas or elevated serum lipids). Accumulation and enlarging size of the atherosclerotic plaque can produce abdominal aortic aneurysms (as opposed to thoracic aortic aneurysms in syphilis, Marfan syndrome, or Takayasu arteritis).
ReKap
In a pediatric patient with a cyanotic congenital heart lesion, a patent ductus arteriosus (PDA) may be lifesaving.
Alprostadil, a prostaglandin E1 (PGE1) analog, can maintain the PDA.
In a typical PDA, closure can be achieved with prostaglandin synthesis inhibitors such as indomethacin or through surgical intervention.
Analysis
The correct answer is A. The infant has both patent ductus arteriosus (PDA) and transposition of the great vessels. Transposition of the great vessels is an abnormal development of the truncoconal septum that results in the inversion of the aorta and pulmonary arteries with respect to the ventricles. Thus, transposition of the great vessels is incompatible with life because the pulmonary and systemic circulations form two independent vascular circuits. A shunt must be present to allow oxygenated blood from the pulmonary circulation to enter the systemic circulation in order for this malady to be compatible with life. Affected babies develop early cyanosis and right ventricular hypertrophy. The prognosis is poor without surgery.
The figure shows the anatomy of the transposition of the great vessels.
In the patient’s case, the PDA provides this lifesaving shunt. Prostaglandins, such as alprostadil or misoprostol, maintain the shunt (i.e., maintain the PDA), so administering a PGE1 analog is necessary until surgical correction of the anomaly can be accomplished. A ventricular septal defect or atrial septal defect can also allow shunting of oxygenated blood to the systemic circulation.
A PDA is a direct communication between the aorta and pulmonary artery. It is normally associated with prematurity and congenital rubella infections. When this condition occurs without concomitant transposition of the great vessels it is treated with NSAIDs, such as indomethacin.
Dexamethasone (choice B) is a glucocorticoid that can accelerate pulmonary maturation in infants with respiratory distress syndrome secondary to lung prematurity. Dexamethasone does not affect the ductus arteriosus.
Indomethacin (choice C) inhibits the formation of prostaglandins and thus would close the PDA. It could be used to treat PDA in an infant without coexisting transposition of the great vessels or another congenital heart disease that requires the duct to be patent.
Nitric oxide (choice D) provides pulmonary vasodilation in the setting of pulmonary hypertension. It would not be effective in maintaining the PDA.
Sildenafil (choice E) is a phosphodiesterase inhibitor. It may be used to induce pulmonary vasodilation. It would not be used to maintain a PDA.
ReKap
A pulmonary emboli arising from a femoral vein thrombosis should be suspected in a bedridden patient who develops sudden onset chest pain, dyspnea, and hypoxemia.
Analysis
The correct answer is A. An estimated 90% of deep vein thrombi (DVT) are formed in the lower extremities. These thrombi may dislodge and travel to distant sites, most importantly to the lungs forming pulmonary emboli. The most frequent cause of pulmonary thromboembolism is DVT of the lower extremities. Pulmonary embolism is estimated to be responsible for 15% of all cases of sudden death.
In this case, the patient’s prolonged bed rest (i.e., immobility) predisposed her to a DVT. Other factors that predispose to clot formation include pregnancy, cancer, or other hypercoagulable states. Some emboli are clinically silent; others affect only those with preexisting cardiac compromise. However, if the clot is large enough, it can cause nearly instantaneous death.
A postoperative patient is at risk of a myocardial infarction (choice B). However, in this case, this is not the most likely scenario. The physical examination and the character of the pain are more indicative of a pulmonary embolism. A pulmonary embolus can cause heart failure, but this is not the primary etiologic event.
Fat emboli (choice C) can occur after a fracture of long bones that releases material from the bone marrow; this is also much less likely than a thromboembolus. The fat particles cause a systemic inflammatory response.
Veins in the upper limbs (choice D) rarely develop thrombosis. This occurs only in disorders leading to a marked thrombotic propensity, such as carcinoma-associated migratory thrombophlebitis (Trousseau syndrome), antiphospholipid antibody syndrome, protein C deficiency, and inherited mutations of the factor V gene.
Deep venous thrombosis typically does not result in clot formation in the pulmonary vein (choice E) because the lungs filter emboli.
ReKap
The venous system contains two-thirds of total blood volume, comprising a reservoir that can be mobilized during hemorrhage to maintain left ventricular preload and cardiac output.
Blood is squeezed from the reservoir by venoconstriction, which raises central venous pressure (CVP) and mean systemic pressure (MSP).
Raising CVP sustains the pressure gradient between veins and the right atrium, thereby ensuring continued forward flow, even as venous capacity and total blood volume decrease.
Analysis
The correct answer is E. The heart relies on blood returning via the venous system for preloading and to sustain output — if there is no venous return, cardiac output (CO) and arterial pressure both drop to zero. Blood flow from the veins to the heart requires a slight pressure differential between the two, with central venous pressure (CVP) being a few mm Hg positive relative to right atrial pressure (RAP).
During hemorrhage, blood loss occurs primarily at the expense of venous volume (see below). The veins constrict to offset this loss and ensure that CVP remains higher than RAP, thereby maintaining forward flow and CO. By “tightening” the circulation and taking up much of the “slack” caused by the blood loss, a near-normal function can usually be maintained with up to 20% loss of blood volume.
Why does blood loss preferentially deplete the venous system? The answer can be found by comparing the capacity and properties of the various components of the vasculature.
Aorta and other large arteries (choice A) are thick-walled, muscular vessels designed to withstand high luminal pressures. They do not contract (aortic contraction would be immediately lethal).
Small arteries (choice D) and arterioles (choice B) are thick-walled, small-bored (i.e., low-capacity), muscular vessels designed to contract to limit forward flow, thereby raising systemic vascular resistance (SVR) and raising mean arterial pressure (MAP).
The combined capacity of arterial system = 11% of total blood volume.
Capillaries (choice C) are thin-walled vessels comprised of an endothelial cell, basement membrane, and no muscle. They do not contract. The combined capacity of capillaries = 4% of total blood volume.
Venules and veins are thin-walled vessels with wide lumens designed to accommodate large volumes of blood. They are equipped with smooth muscle to reduce capacity and thereby raise venous pressure. The high compliance of the venous system and the limited capacity of other vessels means that blood tends to collect in veins.
Total capacity of venous system = 65% of total blood volume = venous blood reservoir.
Physiological differences among arteries, capillaries, and veins.
The venous reservoir is mobilized during hemorrhage by the sympathetic nervous system:
Hemorrhage → ↓ MAP → Baroreceptor reflex
↑Sympathetic output
↑ Heart rate → ↑ CO
↑ Myocardial inotropy → ↑ CO
Venoconstriction → ↓Venous capacity → ↑ CVP → ↑RAP → ↑ Left ventricular preload → ↑ CO
Arteriolar constriction → ↑ SVR → ↑ MAP
The combination of ↑CO and ↑SVR together help preserve MAP during hemorrhage (MAP = CO × SVR).
Mean systemic pressure (MSP) is the pressure that exists within all parts of the system when the heart has been stopped and pressures have equilibrated. The MSP is thus a measure of the “tightness” of the circulatory system. Raising blood volume increases MSP and vice versa.
ReKap
Hyperplastic arteriolosclerosis:
Can be caused by malignant hypertension.
Concentric and laminated “onion skin” arteriolar wall thickening with reduplicated basement membrane.
Smooth-muscle proliferation with associated fibrin deposition and acute vessel wall necrosis.
Can cause acute kidney injury.
Analysis
The correct answer is C. This patient has malignant hypertension, defined as blood pressure >180/120 mm Hg with end-organ damage. Malignant hypertension affects the cardiovascular system, central nervous system, and kidneys. The “onion-skinning” morphology of these arterioles is a feature of hyperplastic arteriolosclerosis (see figure below). Affected vessels may also show necrotizing arteriolitis with acute vessel wall necrosis accompanied by fibrin deposition (fibrinoid necrosis). This type of vessel change is a hallmark of malignant hypertension. Hyperplastic arteriolosclerosis can also be seen with benign hypertension, but does not have the “onion skin” appearance.
Histological sectioning of a renal arteriole affected by hyperplastic arteriosclerosis (left), characterized by a concentric “onion-skinning” morphology in the lumen.
This patient’s anuria results from a narrowing of the renal vessels secondary to hyperplastic arteriosclerosis. This produces an initial pre-renal azotemia followed by acute kidney injury due to decreased perfusion. Other signs of end-organ damage include papilledema (increased intracranial pressure), strokes, myocardial infarction, and retinopathy. Importantly, microangiopathic hemolytic anemia may also result with physical shearing of the red blood cells (resulting in schistocytes on blood smear).
Atherosclerosis (choice A) would produce luminal narrowing by plaques, not onion-skinning, and is more commonly present near the renal artery rather than the smaller arterioles. Atherosclerosis can also produce eventual renal failure due to occlusion of the renal arteries. However, this process is more gradual versus sudden onset as with malignant hypertension.
Hyaline arteriolosclerosis (choice B) typically results from less severe hypertension and diabetes mellitus. It produces a partial narrowing of arterial walls with homogeneously pink hyaline material, not the onion skinning pattern of hyperplastic arteriosclerosis. This is also a more gradual process and results from leakage of plasma components across the vascular endothelium.
Mönckeberg arteriosclerosis (choice D) is characterized by medial (dystrophic) calcification of arteries. Most patients are asymptomatic since the lesions do not cause luminal occlusion.
Polyarteritis nodosa (choice E) is characterized by focal acute inflammation of medium and small arteries. This process presents with vessel wall inflammation, although fibrinoid necrosis can occur.
ReKap
The effects of angiotensin II can be attributed to:
Direct stimulation of sodium reabsorption in the proximal and distal tubules of the kidney.
Stimulation of aldosterone secretion, which is another sodium-retaining hormone.
Constriction of the efferent arteriole increases peritubular colloid osmotic pressure, thereby enhancing reabsorption of salt and water from the proximal tubule.
Analysis
The correct answer is E. Losartan is an angiotensin receptor blocker (ARB) commonly used in the treatment of hypertension that competitively inhibits angiotensin II at the AT1 receptor. The effects of angiotensin II include:
Stimulation of sodium reabsorption in the proximal and distal tubules of the kidney.
Stimulation of aldosterone secretion, which is another sodium-retaining hormone.
Constriction of the efferent arterioles in the kidney, which increases peritubular colloid osmotic pressure and thereby enhances reabsorption of salt and water from the proximal tubule.
Therefore, when the effects of angiotensin II are blocked with losartan, the ability of the kidneys to excrete sodium significantly increases.
Components of the renin-angiotensin-aldosterone system (RAAS) and drugs affecting it.
Angiotensin II normally stimulates aldosterone secretion (choice A), so losartan decreases, not increases, plasma aldosterone levels.
Overstretching of the two atria, usually as a result of increased blood volume, causes atrial natriuretic peptide (ANP; choice B) to be released into the blood. Because losartan increases the ability of the kidneys to excrete sodium (and therefore water), blood volume decreases and the plasma ANP levels also decrease.
Bradykinin (choice C) levels are not affected by ARBs. However, bradykinin levels are increased in patients taking the angiotensin-converting enzyme (ACE) inhibitors because ACE is the enzyme responsible for the metabolism of bradykinin. Increased levels of bradykinin are thought to be the reason patients on ACE inhibitors develop a dry cough. These patients can be switched to ARBs if the dry cough is too aversive to the patient.
Losartan competitively inhibits the binding of angiotensin II to AT1 receptors in vascular smooth muscle and adrenal glands. Inhibition of aldosterone secretion increases sodium and water excretion while decreasing potassium excretion (choice D).
Updated on 08/20/21
ReKap
A potential complication weeks to months after myocardial infarction, especially one that affects the left ventricle, is the formation of a ventricular mural thrombus.
A ventricular mural thrombus develops over an infarcted area where a ventricular aneurysm forms, or over an area affected by ventricular dyskinesia.
Migration of a thromboembolus may precipitate a cerebrovascular accident.
Analysis
The correct answer is E. This patient has suffered a cerebrovascular accident as a consequence of thromboemboli emanating from a ventricular mural thrombus formed over a recently infarcted myocardial area.
A mural thrombus frequently develops over a previously infarcted segment of myocardium, especially when the infarction is large and a ventricular aneurysm develops. Ischemic damage to the endocardium, soluble factors released by the injured myocardium, and altered wall kinetics that produce sluggish blood flow all favor mural thrombus formation. One important consequence of a mural thrombus is thromboembolism to the systemic circulation, producing a stroke, as in this patient’s case.
Calcific coronary atherosclerosis (choice A) is very likely responsible for the patient’s original myocardial infarction. Coronary atherosclerosis is not a consequence of myocardial infarction, and it does not directly predispose to the development of embolic strokes. Complicated atherosclerotic lesions in the carotid or cerebral circulation, however, may directly lead to a cerebrovascular accident.
Electromechanical dissociation (EMD; choice B) is a catastrophic event that frequently leads to sudden cardiac death, not stroke. In EMD, although a wave of depolarization courses through the myocardium, pump action is lost. EMD may occur as a consequence of pericardial tamponade, massive pulmonary embolism, or myocardial toxins that prevent normal cardiac muscle contraction.
Left bundle branch block (choice C) represents the failure of electrical transmission along the Purkinje fibers to the left ventricular myocardium. Bundle branch blocks are important causes of arrhythmia, not cerebrovascular accidents.
Myocardial rupture (choice D) is an infrequent consequence of myocardial infarction that typically occurs 1 week after the infarction. If scarring of the infarcted segment does not keep pace with necrosis and digestion of the infarcted tissue, the myocardium can rupture under the high intraventricular pressures, and pericardial tamponade generally ensues. Myocardial rupture rapidly leads to acute heart failure, not stroke.
ReKap
Burn wounds carry a significant risk of infection due to the breakdown of the protective layers of the skin.
Sepsis causes severe endothelial damage that can increase capillary permeability, leading to severe edema, particularly within the lungs, causing pulmonary edema.
Right heart pressures and pulmonary artery pressures may be elevated in the setting of ARDS but are not always present.
Analysis
The correct answer is E. This patient most likely has sepsis secondary to Pseudomonas aeruginosa as a result of his severe burns. Sepsis is characterized by a systemic inflammatory response that may be complicated by organ dysfunction and failure as the circulatory system collapses. Endotoxin produced by gram-negative bacteria induces the excessive release of pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6, which activate coagulation pathways and lead to endothelial damage and intravascular clotting. Sepsis is the most common cause of acute respiratory distress syndrome (ARDS).
ARDS results from alveolar injury, which causes the release of pro-inflammatory cytokines. Neutrophils are recruited to the lungs by these cytokines, where they become activated and release toxic mediators that damage the alveolar epithelium and capillary endothelium, thereby increasing microvascular permeability. This then allows protein to escape from the vascular space, producing an oncotic gradient, and fluid enters the interstitium, overwhelming the lymphatics. Alveolar spaces become filled with bloody, proteinaceous edema fluid and cellular debris from cells undergoing necrosis. On top of this, functional surfactant is lost, which leads to alveolar collapse (atelectasis). These processes cause impaired gas exchange, decreased lung compliance, and pulmonary hypertension.
Pulmonary edema, caused by increased microvascular permeability, is characterized by an increase in interstitial fluid protein concentration, which increases interstitial colloid osmotic pressure (choice A). Although the increased interstitial colloid osmotic pressure promotes the development of edema, the ultimate cause of the protein leakage into the interstitium is the high permeability of the microvasculature.
Interstitial fluid hydrostatic pressure (choice B) is increased during pulmonary edema. This tends to drive fluid back into the vasculature and opposes edema formation.
Lymph flow (choice C) increases greatly as a consequence of edema (not the cause of edema); were it not for this increase in lymph flow, even greater amounts of fluid would collect in the lungs.
The development of pulmonary edema during sepsis is often exacerbated by concomitant increases in pulmonary microvascular pressure (choice D). However, pulmonary artery pressure and pulmonary capillary wedge pressure (PCWP) are both normal in this patient, suggesting that increased microvascular pressure did not contribute significantly to the development of edema. The PCWP provides an estimate of left atrial pressure, and the pulmonary microvascular pressure is estimated as the average of the pulmonary artery pressure and the pulmonary wedge pressure.
Starling equation describes the contribution of hydrostatic and oncotic forces on the capillary membrane. Increased permeability and increased interstitial oncotic pressure (πIF) lead to the fluid movement responsible for the edema. Increased interstitial fluid hydrostatic pressure would oppose this to some extent, but the effect of protein leakage predominates, and fluid enters the interstitium.
Updated on 06/10/22
ReKap
Marfan syndrome is an autosomal dominant connective tissue disorder caused by mutations in the fibrillin-1 gene located on chromosome 15.
Characteristic features include skeletal abnormalities (tall stature, with arachnodactyly, joint laxity, pectus excavatum or carinatum), cardiac defects (mitral valve prolapse, increased risk of aortic dissection/rupture), and ocular anomalies (lenses subluxation).
Analysis
The correct answer is D. This patient presents with Marfan syndrome, which is an autosomal dominant (AD) genetic disorder of connective tissue characterized by skeletal, ocular, and cardiovascular abnormalities. Marfan syndrome is caused by a mutation in FBN1, a gene that encodes fibrillin-1. Fibrillin-1 serves as scaffolding for the deposition of elastin and the formation of elastic fibers. Affected patients are usually tall, with long legs and tapering fingers. Laxity of joints is present, such that the thumb can be extended back to the wrist. Chest and spinal column deformities (pectus excavatum, kyphoscoliosis) may be present as well.
Elastic fibers are also present in arterial walls and heart valves. As a result, the most frequent cardiovascular anomalies include aortic regurgitation, aortic dissection, and mitral valve prolapse (“floppy valve”). The latter may give rise to mitral regurgitation with the typical auscultatory phenomenon of a midsystolic click followed by a murmur.
Fibrillin also forms a component of the zonules, which suspend and keep tension on the lens of the eye. Thus, a mutation in the FBN1 gene can produce upward dislocation of the lens in these patients. Retinal detachment and glaucoma are also more common in patients with Marfan syndrome.
The collagen disorder, Ehlers-Danlos syndrome (EDS), may present similarly to Marfan syndrome. The classic findings in EDS of skin hyperextensibility and abnormal wound healing, neither of which is characteristic of Marfan syndrome.
Patients with homocystinuria (autosomal recessive deficiency of cystathione beta synthase) can also present with Marfan-like disease due to deposition of homocysteine in connective tissue. Important distinguishing features of homocystinuria include downward lens subluxation (vs. upward in Marfan), hypercoagulability, and seizures/intellectual disability. It is important to note that Marfan syndrome does not affect intellect.
Deficiency of type I collagen (choice A) produces osteogenesis imperfecta (usually AD). Type 1 collagen is an important component of bone and sclera, thus osteogenesis imperfecta patients present with early fractures and blue sclera.
Alterations of type II collagen (choice B) are implicated in some cases of osteochondrodysplasia, which is a cause of dwarfism.
Deficiency of type IV collagen (choice C) is implicated in Alport syndrome and is found in basement membranes. Patients usually present with hematuria (glomerular basement membrane) and sensorineural hearing loss.
Mutations of the gene for fibulin-5 (FBLN5; choice E) can be seen in some cases of cutis laxa, which causes loose, easily stretched skin. Fibulin-5, like fibrillin-1, is required for normal assembly of fibers that give the extracellular matrix elasticity.
ReKap
As a general rule, patients with asthma, emphysema, and chronic bronchitis should not receive β blockers because these agents may cause bronchoconstriction.
β 1-receptor antagonists (cardioselective) can be used more safely in these patients.
Analysis
The correct answer is A. This patient is hypertensive despite the use of the ACE inhibitor enalapril, an appropriate diet, and an exercise program. An appropriate second antihypertensive medication is a beta-blocker, since the use of a thiazide or loop diuretic is contraindicated in this patient due to a severe sulfa allergy. β1-selective antagonists are often used to control hypertension in asthmatic patients who might experience bronchoconstriction with nonselective beta antagonists (e.g., propranolol). Remember that β1 receptors predominate in the heart, whereas β2 receptors predominate in the lungs.
It should also be noted that the β1-selective antagonists begin to lose their specificity as the dose increases. Furthermore, there may be some patients, such as asthmatics and diabetics, who are unable to tolerate even low doses of these agents. Currently, there are no tests that can be performed to determine how well an asthmatic or diabetic, for example, will tolerate one of these agents. However, if an asthmatic or diabetic needs to be prescribed a β blocker, the β 1-selective antagonists are the most appropriate treatment option.
Labetalol (choice B) blocks α1, β1, and β2 receptors and is useful in treating hypertensive emergencies and hypertension secondary to pheochromocytoma.
Nadolol (choice C) blocks both β1and β2 receptors and is known for its very long half-life (14 to 24 hours).
Propranolol (choice D) blocks both β1 and β2 receptors and is used primarily in the treatment of hypertension and migraine prophylaxis.
Timolol (choice E) blocks both β1 and β2 receptors and is frequently used in the treatment of open-angle glaucoma when used topically. This agent is also used orally in the management of hypertension, myocardial infarction, and migraine.
