Coarctation of the aorta, MI and hypertension in pregnancy

MI 1-3 days

Extensive coagulative necrosis (4-72 hours) Neutrophilic infiltrate Inflammation spreads to tissue surrounding infarct. Hyperemia Yellow pallor

ACE and ARBS

ACE inhibitors and angiotensin-receptor blockers (ARB) are contraindicated during pregnancy due to their teratogenic effect!

Wavy myocardial fibres without inflammatory cells

Wavy myocardial fibers without inflammatory cells are typically seen within the first 4 hours post-MI and are followed by coagulative necrosis (4-72 hours post-MI). Common complications during this period include ventricular arrhythmia, heart failure, and cardiogenic shock.

Scotoma

dark spot in the visual field

Hemolysis

↓ Hemoglobin, ↓ haptoglobin, ↑ LDH, ↑ indirect bilirubin

Free wall rupture

A complication of myocardial infarction in which the ventricular wall ruptures due to weakening of the infarcted region. A free wall rupture typically occurs within 2 weeks of an anterior or lateral wall infarct and presents with new-onset chest pain and cardiogenic shock due to cardiac tamponade.

Ventricular pseudoaneurysm

A false aneurysm in which myocardial rupture is contained in the pericardium or scar tissue. Most frequently occurs 3-7 days after myocardial infarction.

Right ventricular outflow obstruction

A right ventricular outflow obstruction (RVOU) is typically seen in patients with tetralogy of Fallot. While patients with tetralogy of Fallot can also have a systolic ejection murmur, it is usually best heard at the left sternal border, rather than the left paravertebral region, as is the case in this patient. Furthermore, such patients usually present with (mild) cyanosis and intermittent hypoxic episodes that improve with squatting, none of which is present in this patient.

Magnesium Sulfate

A substance that is used intravenously to prevent convulsions in patients with pre-eclampsia or acute nephritis, to provide neuroprotection for premature infants (given to mother before birth), as a tocolytic agent, to treat torsades de pointes syndrome, and to correct hypomagnesemia. Magnesium sulfate is also used as a component of hygroscopic dressings, and orally as a laxative. Prophylaxis for eclampsia

Granulation tissue

A type of connective tissue generated by fibroblasts during wound healing. Initially, it is composed of type III collagen, which is then replaced by type I collagen to create a stronger extracellular matrix.

Elevated liver enzymes in HELLP

AST and ALP

GGT

Gamma GT is an abbreviation for glutamytransferase, which is an enzyme found in liver cells and the biliary tract. It is a very sensitive indicator of abnormality in the liver or bile duct system.

An increased R wave amplitude in V5-V6 on ECG

An increased R wave amplitude in V5-V6 on ECG can be a sign of left ventricular hypertrophy. While myocardial hypertrophy is one of the compensatory mechanisms to counter the aortic narrowing in patients with coarctation of the aorta such as this 2-year-old boy, the changes in ECG vary with age and degree of stenosis, and it usually takes several years before the hypertrophy becomes apparent. In older children and adults, ECG may show signs of left ventricular hypertrophy in the left precordial leads (e.g., positive Sokolow-Lyon criteria).

Calcium gluconate

Antidote for magnesium sulfate

A 36-year-old primigravid woman comes to the physician for a prenatal visit at 14 weeks' gestation. She has had episodic headaches over the past month. At home, blood pressure measurements have ranged from 128/82 mm Hg to 140/83 mm Hg. Today, her blood pressure is 138/84 mm Hg. Pelvic examination shows a uterus consistent in size with a 13-week gestation. Serum creatinine is 0.8 mg/dL, serum ALT is 17 U/L, and platelet count is 320,000/mm3. Urinalysis shows no abnormalities. Which of the following is the most likely diagnosis?

Chronic hypertension

Coagulative necrosis with dense neutrophilic infiltrate

Coagulative necrosis with dense neutrophilic infiltrate is typically seen 1-3 days post-MI. The most important complication during this period is post-infarction fibrinous pericarditis.

Acute fatty liver of pregnancy

Definition: a rare disease most common in the third trimester characterized by extensive fatty infiltration of the liver, which can result in acute liver failure Pathophysiology: Dysfunction of fatty acid β-oxidation Symptoms Sudden onset of jaundice RUQ pain, nausea, and vomiting Coagulopathy (Decreased hepatic production of coagulation factors due to impaired liver function) with an increased risk of disseminated intravascular coagulation (DIC) Hypoalbuminemia (Albumin is produced in the liver. Reduced levels of albumin are due to the fatty infiltration of the liver with subsequent liver cell damage.) → ascites Complications: Acute liver failure Acute renal failure Encephalopathy Fetal and maternal death (10%) Diagnosis Laboratory analysis: ↑ AST, ↑ALT (In most cases GLDH and γ-GT are not elevated.) ↑ WBC, ↓ platelets Hypoglycemia Liver synthesis parameters: ↓↓ clotting factors (Factors IX, X, VII, II, Protein S, Protein C), ↓↓ Cholinesterase Imaging: rule out other diagnoses (e.g., liver hematoma) Therapy: immediate Cesarean (C)-section

Intrahepatic cholestasis of pregnancy

Definition: a rare disease most common in the third trimester that presents with pruritus, jaundice, and an elevation in serum bile acid concentrations Epidemiology: Intrahepatic cholestasis occurs in 0.1-0.2% of pregnancies. Etiology: Multifactorial (Including genetic predisposition, exogenous factors and an increased sensitivity to high estrogen levels during pregnancy.) Symptoms Jaundice Pruritus Complications Fetal growth restriction Increased fetal mortality Premature labor and increased preterm birth rates Recurrence in following pregnancies (40-60%) Diagnosis ↑ Total serum bile acid levels (cholic acid and chenodeoxycholic acid) > 10 micromol/L ↑ ALP ↑ ALT, AST ↑ direct bilirubin Hepatitis serology (to rule out viral hepatitis) Antismooth muscle and antimitochondrial antibodies (to rule out autoimmune liver disease) Therapy First-line medication: ursodeoxycholic acid PO Cholestyramine PO → may cause a deficiency in fat-soluble vitamins and lead to related adverse effects Prognosis: fully reversible postpartum

Dense granulation tissue with collagenous scar formation

Dense granulation tissue with collagenous scar formation is typically seen 2-8 weeks post-MI. Common complications during this period include true ventricular aneurysm and Dressler syndrome.

MI 0-24 hours

Early coagulative necrosis (> 4 hours) Release of inflammatory cytokines from necrotic cells → edema, hemorrhage Recruitment of neutrophils (granulocytes) Hypercontraction of myofibrils → wavy fibers Contraction band necrosis (if reperfusion injury has occurred) 0-12 hours: no gross changes 12-24 hours: dark mottling

Eclamptic Seizure

Generalized tonic-clonic seizures Deterioration with headaches, RUQ pain, hyperreflexia, and visual changes are warning signs of a potential eclamptic seizure! Hypertensive pregnancy disorders may be intrapartum or postpartum. In some cases, eclamptic seizures may occur postpartum.

GLDH

Glutamate dehydrogenase (GLDH, GMD, GLD, and GDH) is a mitochrondrial enzyme that catalyzes the conversion of glutamate to 2-oxoglutarate. Increases in GLDH activity are used primarily to reflect leakage from damaged or necrotic hepatocytes. Since it is quite a large mitochondrial enzyme, injury needs to be sufficiently severe to damage mitochondria GLDH is located more in the centrilobular areas of the liver, whereas AST is more homogenously distributed and ALT is more periportal

MI 2 weeks to several months

Granulation tissue becomes more dense → collagenous scar formation Grayish white fibrosis

HELLP syndrome

HELLP syndrome: a life-threatening form of preeclampsia (HELLP is an acronym: H = hemolysis; EL = elevated liver enzymes; LP = low platelets) A complication of pregnancy and form of preeclampsia that most commonly occurs > 27 weeks' gestation. Characterized by hemolysis (H), elevated liver (EL) enzymes, and low platelet (LP) count. Other features include abdominal pain and rapid clinical deterioration (due to severe systemic inflammation causes multiorgan failure). Treatment includes stabilization (e.g., fluid resuscitation, antihypertensive therapy) and delivery of the fetus.

Preeclampsia

Headache in a patient with the onset of hypertension before 20 weeks' gestation merits a diagnosis of superimposed preeclampsia if it is accompanied by other features of cerebral edema such as visual blurring, vomiting, or altered mental status, if the headache is severe and persistent, and/or if other features of preeclampsia (e.g., proteinuria, renal insufficiency, elevated liver enzymes, thrombocytopenia, and pulmonary edema) are present. This patient, however, has a normal urinalysis and normal blood test results, and no features of cerebral or pulmonary edema.

An 80-year-old man is admitted to the hospital after the sudden onset of sub-sternal chest pain and shortness of breath while sitting in a chair. He has hypertension and type 2 diabetes mellitus. He has smoked 1 pack of cigarettes daily for 42 years. Four days after admission, he becomes tachycardic and then loses consciousness; the cardiac monitor shows irregular electrical activity. Cardiac examination shows a new systolic murmur at the apex. Despite appropriate measures, he dies. Microscopic evaluation of the myocardium is most likely to show which of the following?

Hyperemic granulation tissue with abundance of macrophages This patient's murmur is consistent with acute mitral regurgitation and in the setting of recent chest pain, is most likely due to papillary muscle rupture from myocardial infarction. Other complications that can occur 4 days after myocardial infarction include free wall rupture and interventricular septal rupture.

Hyperemic granulation tissue with abundance of macrophages

Hyperemic granulation tissue with abundance of macrophages is typically seen 3-10 days post myocardial infarction. The complications during this period usually arise due to macrophage-mediated removal of necrotic tissue. They include free wall rupture, left ventricular pseudoaneurysm, papillary muscle rupture, and interventricular septal rupture.

Low tissue oxygenation in the legs

In patients with coarctation of the aorta, the blood supply to all tissues distal to the aortic narrowing is limited, including the lower extremities. The resulting hypoxia becomes evident especially during exertion, presenting as intermittent lower-extremity claudication as in this patient.

Interarm difference in BP

Interarm differences in blood pressure can be a finding of coarctation of the aorta in the rare case that the narrowing is proximal to the left subclavian artery. However, in such patients, blood pressure in the right arm would be higher than in the left arm rather than the other way around. In this patient, we would instead expect differences in blood pressure between the upper and the lower extremities.

Isolated systolic hypertension

Isolated systolic hypertension is characterized by elevated systolic BP and normal diastolic BP (and widened pulse pressure), which is usually the result of decreased arterial compliance. This patient's diastolic BP, which is > 80 mm Hg, is not consistent with isolated systolic hypertension.

Low cellularity with dense, non-contractile scar tissue

Low cellularity with dense, non-contractile scar tissue is typically seen 2 months post-MI. Common complications during this period include heart failure, arrhythmia, true ventricular aneurysm, and Dressler syndrome.

A 2-year-old boy is brought to the physician by his parents because of difficulty walking and cold feet for the past 2 months. His parents report that he tires quickly from walking. The patient was born at 37 weeks' gestation and has met all developmental milestones. There is no personal or family history of serious illness. He is at the 50th percentile for height and 40th percentile for weight. His temperature is 36.9°C (98.4°F), pulse is 119/min, respirations are 32/min, and blood pressure is 135/85 mm Hg. A grade 2/6 systolic murmur is heard in the left paravertebral region. Pedal pulses are absent. Further evaluation of this patient is most likely to show which of the following findings?

Low tissue oxygenation in the legs This patient has evidence of easy fatigability, hypertension, a low-grade systolic ejection murmur, lower-extremity claudication, and diminished lower-extremity pulses suggesting a diagnosis of coarctation of the aorta.

MI 3-14 days

Macrophage infiltration Granulation tissue surrounds infarct margins (3-10 days) Proliferation of blood vessels into granulation tissue (10-14 days) Hyperemic border Center: yellow-brown, soft

Ursodeoxycholic acid

Medication used to dissolve small gallstones in patients who are poor surgical candidates Also, the treatment for Primary Biliary Cirrhosis Specific bile acid that inhibits intestinal absorption of cholesterol and reduces hepatic synthesis and secretion of endogenous cholesterol. It is recommended for the treatment of primary biliary cholangitis due to anti-apoptotic and immunomodulatory effects and as a litholytic agent in gallstone disease (radiolucent cholesterol stones < 20 mm).

Placental hypoperfusion

Multiple maternal, fetal, and placental factors are involved in placental hypoperfusion, which leads to maternal hypertension and other consequences. Abnormal placental (or trophoblast) implantation or development in the uterus → hypoperfusion of placenta and fetus Arterial hypertension with systemic vasoconstriction causes placental hypoperfusion → release of vasoactive substances → ↑ maternal blood pressure to ensure sufficient blood supply of the fetus Systemic endothelial dysfunction causes placental hypoperfusion → ↑ placental release of factors (E.g., vascular endothelial growth factor (VEGF) and placental growth factor (PGF) ) → endothelial lesions that lead to microthrombosis

Rib notching

Notching of the ribs can be visualized on x-ray in patients with coarctation of the aorta, such as this boy, when compensatory collateral blood flow involves the intercostal vessels. Those vessels may dilate to bypass the left ventricular outflow tract obstruction. While this patient may eventually develop visible rib notching, it is generally a sign of chronic disease and usually does not become apparent in children before the age of 5 years.

Consequences of vasoconstriction and microthrombosis

Organ ischemia and damage Preeclampsia: multiorgan involvement (primarily renal) Eclampsia: predominantly cerebral involvement HELLP syndrome: severe systemic inflammation with multiorgan hemorrhage and necrosis (particularly liver involvement) Chronic hypoperfusion of the placenta → insufficiency of the uteroplacental unit and fetal growth restriction

Kidney

Pathomechanism: Glomerular endothelial dysfunction and hypertension-induced vasoconstriction Disorder: Oedema (renal hypoperfusion and water retention), proteinuria and impaired renal function Occurrence: Preeclampsia Eclampsia HELLP syndrome

CNS

Pathomechanism: Hypertension-induced vasoconstriction and endothelial damage → disruption of cerebral microcirculation with microthrombi → vasospasms in the CNS Disorder: Seizures Occurrence: Eclampsia

Lung

Pathomechanism: Increased systemic vascular resistance and volume overload (due to renal water retention) → left ventricular dysfunction → ↑ pulmonary capillary hydrostatic pressure, ↑ capillary permeability (due to endothelial dysfunction) , and ↓ albumin Disorder: Pulmonary oedema Respiratory distress Occurrence: Severe preeclampsia HELLP syndrome

Blood

Pathomechanism: Systemic microthrombi and vasoconstriction → overactivation of the coagulation system and platelet consumption Microangiopathic hemolysis Disorder: Disseminated intravascular coagulopathy (œ) Thrombocytopenia Anemia Occurrence: HELLP syndrome Severe preeclampsia

Liver

Pathomechanism: Vasoconstriction and microthrombotic obstruction of liver sinusoids → liver cell damage Disorder: Liver impairment and hepatomegaly Occurrence: HELLP syndrome Severe preeclampsia Eclampsia

Peripheral smear

Peripheral smear (assess for hemolysis) and coagulation studies are indicated if HELLP syndrome is suspected (i.e., thrombocytopenia and/or liver function impairment are present) DIC: ↑ D-dimers, ↓ fibrinogen, ↓ AT III

Dressler's syndrome

Post-MI fibrinous pericarditis An acute pericarditis that occurs 2-10 weeks after myocardial infarction. Postmyocardial infarction syndrome likely occurs because neo-antigens released from the injured myocardium combine with antibodies to form immune complexes, which elicit an inflammatory response.

Placental abruption

Premature separation of the placenta from the uterine wall after 20 weeks' gestation and before the fetus is delivered. Most commonly due to hypertension

Preeclampsia with severe features

Severe hypertension (systolic ≥ 160 mmHg or diastolic BP ≥ 110 mmHg) Proteinuria, oliguria Headache Visual disturbances (e.g., blurred vision, scotoma) RUQ or epigastric pain (Liver (Glisson's) capsule strain due to swelling of the liver) Pulmonary edema Cerebral symptoms (e.g., altered mental state, nausea, vomiting, hyperreflexia, clonus)

B-oxidation

The breakdown of triglycerides into smaller subunits called free fatty acids (FFAs) to convert FFAs into acyl-CoA molecules, which then are available to enter the Krebs cycle and ultimately lead to the production of additional ATP. A catabolic process in which a fatty acid chain is cleaved at the β carbon (every 2nd carbon) by dehydrogenase enzymes. Breaks down odd-chain fatty acids into acetyl-CoA and propionyl CoA and even-chain fatty acids into acetyl-CoA only. Typically occurs in the mitochondria; β-oxidation of very long-chain fatty acids occurs in peroxisomes.

Chronic hypertension

The onset of hypertension (i.e., systolic BP ≥ 130 mm Hg and/or diastolic BP ≥ 80 mm Hg) before 20 weeks' gestation, prior to pregnancy, or persisting beyond 6 weeks after giving birth, is known as chronic or preexisting hypertension and is not due to the pregnancy itself. Complications of hypertension in pregnancy include fetal growth restriction, preterm birth, placental abruption, and superimposed preeclampsia.

Gestational hypertension (GH)

This disorder begins after the 20th week of pregnancy where BP s elevated at 140/90 mm Hg or greater recorded at least twice, 4-6 hours apart within a 1 week period Asymptomatic hypertension Nonspecific symptoms (e.g., morning headaches, fatigue, dizziness) can occur.

Causes of thrombocytopenia and liver impairment during pregnancy

Thrombotic microangiopathy (TTP, HUS) Fulminant viral hepatitis

Preeclampsia without severe features

Usually asymptomatic Nonspecific symptoms may include: Headaches Visual disturbances RUQ or epigastric pain Rapid development of edema Hypertension Proteinuria Preeclampsia (gestational hypertension with proteinuria, renal insufficiency, elevated liver enzymes, headache, and/or visual symptoms) without any of the following severe features: systolic blood pressure > 160 mm Hg or diastolic > 110 mm Hg, platelet count < 100,000, markedly elevated liver enzymes or RUQ pain, worsening renal insufficiency, pulmonary edema, severe persistent headache, or persistent/worsening visual symptoms.

Uterine spiral arteries

Uterine spiral arteries normally develop to high-capacity blood vessels. This process is defective in patients with preeclampsia.

Disseminated Intravascular Coagulation (DIC)

abnormal blood clotting in small vessels throughout the body that cuts off the supply of oxygen to distal tissues, resulting in damage to body organs In DIC, the processes of coagulation and fibrinolysis are dysregulated, and the result is widespread clotting with resultant bleeding. Tissue factor released in response to cytokines (IL-1), TNF and endotoxin TF binds with activated factor VIIa forming the extrinsic tenase complex Further activating IX and X to IXa and Xa, leading to the common coagulation pathway

Coarctation of the aorta

narrowing of the descending portion of the aorta, resulting in a limited flow of blood to the lower part of the body A congenital heart defect that involves the narrowing of the aorta at the aortic isthmus. Frequently associated with other congenital heart defects (e.g., bicuspid aortic valve, VSD and/or PDA) and Turner syndrome.

Claudication

pain, tension, and weakness in a leg after walking has begun, but absence of pain at rest A cramping pain induced by exercise. Caused by arterial insufficiency and subsequent ischemia, typically in the lower legs.

Eclampsia

true toxemia of pregnancy characterized by high blood pressure, albuminuria, edema of the legs and feet, severe headaches, dizziness, convulsions, and coma