Lecture notes

Obesity , as known from various Studies, is an associated cause for increase in morbidity and mortality. There is  50–100% increase in risk of death from all causes compared to normal weight people, mostly due to cardiovascular causes. Mortality rates rise as obesity increases, particularly when obesity is associated with increased intraabdominal fat . Life expectancy of a moderately obese individual could be shortened by 2–5 years, and a 20- to 30-year-old male with a BMI > 45 may lose 13 years of life. It is also apparent that the degree to which obesity affects particular organ systems is influenced by susceptibility genes that vary in the population.

Insulin Resistance and Type 2 Diabetes Mellitus

Obesity  is a major risk factor for diabetes, and as many as 80% of patients with type 2 diabetes mellitus are obese.

Hyperinsulinemia and insulin resistance are pervasive features of obesity, increasing with weight gain and diminishing with weight loss . Insulin resistance is more strongly linked to intraabdominal fat than to fat in other depots. The molecular link between obesity and insulin resistance in tissues such as fat, muscle, and liver has been sought for many years.

Major factors under investigation include:

(1) insulin itself, by inducing receptor downregulation;

(2) free fatty acids, known to be increased and capable of impairing insulin action;

(3) intracellular lipid accumulation; and

(4) various circulating peptides produced by adipocytes, including the cytokines TNF- and IL-6, RBP4, and the “adipokines” adiponectin and resistin, which are produced by adipocytes, have altered expression in obese adipocytes, and are capable of modifying insulin action.

Weight loss and exercise, even of modest degree, are associated with increased insulin sensitivity and often improve glucose control in diabetes.
Also read Dieting for weight control : good or bad

Reproductive Disorders

Males-

• Male hypogonadism is associated with increased adipose tissue, often distributed in a pattern more typical of females.
• In men >160% ideal body weight, plasma testosterone and sex hormone–binding globulin (SHBG) are often reduced, and estrogen levels  are increased.
• Gynecomastia.

Females-

• menstrual abnormalities in women, particularly in women with upper body obesity.
• increased androgen production, decreased SHBG, and increased peripheral conversion of androgen to estrogen.
• may be associated with polycystic ovarian syndrome (PCOS), with its associated anovulation and ovarian hyperandrogenism; 40% of women with PCOS are obese.
• lower body obesity  may contribute to the increased incidence of uterine cancer in postmenopausal women with obesity.

Cardiovascular Disease

• coronary disease – Read on Acute MI
• stroke
• and congestive heart failure (CHF).

The waist/hip ratio may be the best predictor of these risks.

• Obesity-induced hypertension is associated with increased peripheral resistance and cardiac output, increased sympathetic nervous system tone, increased salt sensitivity, and insulin-mediated salt retention; it is often responsive to modest weight loss.

Pulmonary Disease

• Reduced chest wall compliance,
• increased work of breathing,
• increased minute ventilation due to increased metabolic rate,
• and decreased functional residual capacity and expiratory reserve volume
• Severe obesity may be associated with obstructive sleep apnea and the “obesity hypoventilation syndrome” with attenuated hypoxic and hypercapnic ventilatory responses

Gallstones

higher incidence of gallstones, particularly cholesterol gallstones

Cancer

• Males-

cancer of the esophagus,colon,rectum,pancreas,liver, and prostate

• Females -

cancer of the gallbladder, bile ducts, breasts, endometrium, cervix, and ovaries.

Bone, Joint, and Cutaneous Disease

• Obesity is associated with an increased risk of osteoarthritis, no doubt partly due to the trauma of added weight bearing and joint malalignment.
• The prevalence of gout may also be increased
• Among the skin problems associated with obesity is acanthosis nigricans, manifested by darkening and thickening of the skin folds on the neck, elbows, and dorsal interphalangeal spaces. Acanthosis reflects the severity of underlying insulin resistance and diminishes with weight loss.
• Friability of skin may be increased, especially in skin folds, enhancing the risk of fungal and yeast infections. Finally, venous stasis is increased in the obese.

Source: Harrison’s Internal Medicine Book

DEFINITION:

Interstitial edema, including fluid engorgement of the perivascular and peribronchial spaces and the alveolar wall interstitium.

ETIOLOGY:

Arrhythmias , MI , severe systemic hypertension

Pulmonary embolism , valvular heart disease

Increased pulmonary capillary wedge pressure

PATHOPHYSIOLOGY:

Cardiogenic pulmonary edema occurs when the pulmonary capillary pressure exceeds the forces that maintain fluid within the vascular space (serum oncotic pressure and interstitial hydrostatic pressure).

Increased pulmonary capillary pressure may be caused by LV failure of any cause , obstruction to transmitral flow (mitral stenosis, atrial myxoma) or rarely pulmonary veno-occlusive disease.

Accumulation of fluid in the pulmonary interstitium is followed by alveolar flooding and impairment of gas exchange.

DIAGNOSIS:

CLINICAL PRESENTATION:

Signs and Symptoms:

Dyspnea, increased respiratory rate,

Cough with expectoration( pink frothy sputum)

Cyanosis , anxiety, restlessness, nocturnal dyspnea

Physical signs of decreased peripheral perfusion, pulmonary congestion (rales) , use of accessory respiratory muscles and wheezing.

IMAGING AND DIAGNOSTIC STUDIES:

Chest X-ray findings:

pulmnonary edema

Prominent pulmonary vessels: interstitial and perihilar vascular engorgement, abnormal distension of upper lobe pulmonary veins, right and left pulmonary arteries dilate

Cardiomegaly: enlarged cardiac silhouette

Kerley B line: interstitial edema causes thickened interlobular septa and dilated lymphatics; these are evident as horizontal lines in the costophrenic angles.

Pleural effusions

Reticular shadowing: hazy opacification spreading from hilar region due to alveolar edema

Arterial Blood Gases:

Decreased partial pressure of arterial oxygen (PaO2).

Early on: normal to decreased partial pressureof arterial CO2 (PaCO2) , serum bicarbonate and respiratory alkalosis.

Late stages: increased PaCO2 , serum bicarbonate and respiratory acidosis.

ECG: to determine if arrhythmia is contributing to the development of pulmonary edema.

TREATMENT

Initial Management

-Supplemental oxygen(high flow, high concentration) should be administered initially to raise the arterial oxygen tension to >60mm Hg. Non-invasive positive pressure ventilation (continuous positive airway pressure CPAP, of 5-10 mm Hg) by a tight fitting face mask results in more rapid improvement.

-Placing the patient in sitting position reduces pulmonary congestion and improves pulmonary function.

-Strict bed rest, pain control, and relief of anxiety can decrease cardiac workload.

-Mechanical ventilation is indicated if oxygenation is inadequate by noninvasive means or if hypercapnia coexists.

-Precipitating factors should be identified and corrected.

MEDICATIONS:

sympathetically mediated peripheral vasoconstriction thus dilates pulmonary and systemic veins.

-Morphine 2-5 mg IV , can be given over several minutes and can be repeated every 10-25 minutes until an effect is seen.

Furosemide a loop diuretics is a venodilator that decreases pulmonary congestion within mins of IV administration. 20-80 mg IV should be given over several minutes.

Nitroglycerin IV is preferable to reduce preload and potentiate the effect of furosemide.

Nitroprusside is effective in treatment of CPE that results from valvular regurgitation or HTN.

Inotropic agents such as dobutamine or phosphodiesterase inhibitors may be helpful in patients with concomitant hypotension or shock.

Digoxin if in atrial fibrillation.

Recombinant BNP (nesiritide) administered as IV bolus followed by an IV infusion. Nesiritide reduces intracardiac filling pressures by producing vasodilation and indirectly increases the cardiac output.

Definition:

Myocardial infarction (MI) or acute myocardial infarction (AMI), is the interruption of blood supply to part of the heart, causing heart cells to die, commonly due to occlusion (blockage) of a coronary artery following the rupture of a vulnerable atherosclerotic plaque, which is an unstable collection of lipids and white blood cells in the wall of an artery.

The resulting ischemia and oxygen shortage, if left untreated for a sufficient period of time, can cause damage or death (infarction) of heart muscle tissue (myocardium).

Clinical Presentation:

Symptoms:

• Pain is the cardinal symptom. Chest pain is often described as tightness, heaviness, crushing or squeezing in the chest. It is retrosternal and often radiates down the left arm , neck, epigastrium or back and sometimes the jaw , usually more severe and lasts longer than angina. Painless MI is seen in older and diabetic patients.
• Diaphoretic, pale ,cool moist skin, anxiety and fear of impending death.
• Breathlessness
• Nausea and vomiting common in inferior wall MI
• Collapse and syncope due to arrhythmia or profound hypotension.

Signs:

Signs of sympathetic activation- pallor, sweating, tachycardia

Signs of vagal activation- vomiting, bradycardia

Signs of impaired myocardial function- hypotension, oliguria, cold peripheries narrow pulse pressure raised jugular venous pressure (right ventricular infarct) third heart sound quiet first heart sound ,diffuse apical impulse lung crepitations.

Signs of tissue damage- fever

Signs of complication- mitral regurgitation, pericarditis

Diagnostic tests:

ECG-the earliest sign is usually ST elevation (appears within minutes)

Progressive loss of R wave , developing Q wave, resolution of ST elevation and terminal T wave inversion.(within hrs)

Deep Q wave and T wave inversion.(within days)

Old or established infarct pattern; Q wave tends to persist but the T wave changes become less marked.(after several weeks or months)

a) Transmural (Q wave) MI

-presence of ST elevation with subsequent development of pathologic Q waves.

Pathologic Q waves have a width of 0.04 seconds or more and an amplitude >=25% of the R wave in that lead.

MI can be classified based on the location of the Q waves:

Inferior MI:Q waves in II, III, aVF

High lateral MI:Q waves in I,Avl

Anteroseptal MI: Q waves in V1 through V3

Anteroseptal MI: Q waves in V4 through V6

Localized anterior MI:Q waves in V2 through V4

Anterior MI: Q waves in V1 through V6, I,aVL

Right ventricular MI:Q waves in V4 and V5

Posterior wall MI: large R in both V1 and V2 and Q in V6

b) Non Q wave MI:

involves subendocardial zone of left ventricle

does not exhibit any abnormal Q waves or ST elevation

exhibits marked ST segment depression of 1mm or more resulting in either horizontal or down-sloping ST segments in all precordial leads.

Cardiac Enzymes:

Enzyme                  Rise(hrs)                 Peak(hrs)                  Return to baseline(days)

troponin                      3-6                          12-24                                       7-10

CK-MB                          4-6                          12-36                                         3-4

LD                                   12                            24-48                                      10-14

Other blood tests: leucocytosis, ESR raised C-reactive protein raised

Chest X-ray: demonstrate pulmonary edema , cardiomegaly due to pre-existing myocardial damage.

Echocardiography: assessing left and right ventricular function and detecting important complications such as mural thrombus, cardiac rupture, VSD, mitral regurgitation and pericardial effusion.

Treatment:

1) Medical therapy

a) IV-O2 monitor

b) NTG-0.4 mg sublingually repeated every 2-5 minutes upto 3 times, if no relief use 5-10mg/min IV at 2-5 min intervals to a max. of 100mg/min

c) Aspirin : 160- 300mg PO preferably chewed

d) B blockers- cardioselective (B1 ) blockers

metoprolol:5-15mg IV over 5min

atenolol: 5-10 mg IV over 5min

e) Morphine: 2 mg IV bolus every 5 minutes titrated to effect

f) Magnesium: def. produce cardiac arrhythmias , secondary hypokalemia . 1-2g IV over 10-20 minutes followed by continuous infusion 1-2g/h

g) Thrombolytics: streptokinase, urokinase, anisoylated plasminogen streptokinase activator complex(APSAC, anistreplase), alteplase, retaplase.

Indications:

-Acute MI by ECG criteria of >0.1mV ST segment elevation in at least two contiguous leads or new left bundle branch block

-Absence of cardiogenic shock.

Administered in<6hrs most beneficial.

(note:-Thrombolytics are used in TT of MI but not unstable Angina)

h) arterial vasodilators:- are used in left and right ventricle infarct.

i) GP IIb-IIIa receptor inhibitors: used for non Q wave MI

j) Subcutaneous heparin(12,500U twice daily), given in addition to oral aspirin, may prevent reinfarction after successful thrombolysis and reduce risk of thromboembolic complications.

2) Surgical therapy

a)Percutaneous coronary transluminal angioplasty (PTCA)

b)Coronary artery bypass grafting (CABG)