Mechanisms Of Human Disease- Small Group Session

Arcot J. Chandrasekhar, M.D.

Clinical Pearls To Take To Clinical Years

Acid Base

Anemia

  1. MCV divides anemia in micro, normo, and macrocytic types.
  2. Reticulocyte count helps to categorize anemia into hypo or hyper proliferative type. Corrected reticulocyte count = % reticulocyte X (patient's hct/expected normal hct of 40).
  3. Microcytic: Abnormal hemoglobin synthesis; Macrocytic: A maturation defect (B12, Folate deficiency) .
  4. In post menopausal women and males consider colon cancer as the etiology for iron deficiency anemia.
  5. Iron deficiency anemia in menstruating women is mostly due to excessive menstrual loss of blood and multiple pregnancies.

Angina

  1. Angina is a diagnosis made from history. Characteristic pain related to activity.
  2. HTN, DM, hypercholesterolemia, cigarette smoking and family history are risk factors.
  3. Exercise EKG, exercise nuclear medicine study and coronary angiograms are supplemental diagnostic studies.
  4. Sublingual nitroglycerin provides dramatic relief. Beta-blockers and calcium channel blockers may be necessary for better control.

Autoimmune

Calcium and Bone

Chronic Bronchitis

  1. Chronic bronchitis is a diagnosis based on history: cough for three months out of the year for more than two years.
  2. Asthma, chronic bronchitis and emphysema present as chronic obstructive lung disease (COPD).

CNS Viruses

Congestive Heart Failure

  1. Decrease metabolic need. Oxygen demand supply ratio: Bed rest, xxygen, decrease catecholamine activity (beta-blockers).
  2. To reduce venous return (pre-load): Elevate head end of bed, nitrates, diuretics (Furosemide) (old tricks: alternating tourniquet, phlebotomy).
  3. Increase cardiac output: Inotropic agents: dopamine, dobutamine, amrinone, milrinone, digoxin (chronic chf) nitropress.
  4. Reduce work load: Reduce after-load: Peripheral vascular resistance. Arterial dilatation (nitrates, nitropress) IABP.
  5. Underlying cause: Diastolic dysfunction (reduce blood pressure) replacing stenotic valve.
  6. Eliminate contributing factors: Anemia.
  7. Counter deleterious compensatory efforts: Rennin agiotensin system. Salt and water restriction, ACE inhibitors (Captopril, Enalpril).
  8. Analgesics and Anxiolytic: Morphine (pulmonary edema).
  9. Cardiac transplantation: Last resort to a completely failed heart refractory to therapy.
  10. Mechanical ventilation: In severe cases of pulmonary edema. To support ventilation. Provide rest to myocardium. To control pulmonary edema.
  11. Dialysis: Combined renal and heart failure.

Diabetes Mellitus

  1. Causes of polyuria include diabetes mellitus, hypokalemia, hypercalcemia, excessive water ingestion, nephrogenic diabetes insipidus and central diabetes insipidus.
  2. As long as the patient is urinating properly, most patients need potassium replacement as part of early treatment of DKA to avoid hypokalemia, which might cause cardiac arrest or fatal arrhythmias.
  3. Ideal body weight can be calculated from several formulas (one for adult males suggests 110 pounds for 5 feet of height, and 5 pounds for each additional inch; for females it is the same, but at 100 pounds for 5 feet of height).
  4. For an ideal body weight of 140 pounds needs can be approximately calculated by multiplying 10 calories per pound for basal requirements, plus 3 calories per pound for sedentary activity. (For moderate activity, 6 calories x pound; for intense activity, 9 calories x pound.)
  5. For weight reduction, there should be about 500 calories of deficit a day, which should be subtracted from patient's daily needs.
  6. Macro vascular risk factors.(Coronary artery disease, Cerebro vascular disease and Peripheral vascular disease)
  7. Micro vascular risk factors (Retinal and Renal).
  8. Diabetic control should be tight and aim for HbA1c below 7.
  9. Aim to maintain serum cholesterol below 180 mg and LDL below 100.
  10. Aim of therapy for hypertension should be to maintain BP to 140/90.

Diarrhea

  1. Diarrhea lasting two weeks or less is considered to be acute diarrhea.
  2. Diarrhea lasting longer than two weeks or is intermittent over months or years is considered chronic diarrhea.
  3. Acute diarrhea lasts two weeks or less, self-limited requiring no diagnostic work-up symptomatic treatment only (fluids).
  4. Acute diarrhea should be investigated only if there is evidence of tissue invasion such as blood or pus in the stool, fever, leukocytosis, severity that produces significant fluid and electrolyte loss.
  5. Chronic diarrhea lasts longer than two weeks or is intermittent over months or years This form requires a diagnostic work-up and a treatment strategy.
  6. Inflammatory diarrhea: shigella, campylobacter, salmonella, histolytica, clostridium, e coli
  7. Chronic diarrhea can be classified as follows:
    1. Steatorrhea: Passage of stools containing an excessive amount of fat (>7 gm fecal fat/24 hrs or more than 10% of ingested fat).
    2. Watery diarrhea osmotic diarrhea: A consequence of increased amounts of poorly absorbable, osmotically active solutes in the lumen of the intestine.
    3. Secretary diarrhea: Secretion of electrolytes and water exceed absorption or absorption of electrolytes and water are impaired.
    4. Exudative inflammation of the bowel mucosa may result in loss of pus, mucus, blood, protein intestinal dysmotility.

ENT Infections

  1. Normal oral flora (pneumococcus, hemophalus) is responsible for infections of sinuses, middle ear infections and acute pharyngitis.
  2. Blockage of ostea for sinuses and eustacean tube for middle ear are important predisposing factors for infection.
  3. Viruses and strep pneumonia are the most common organisms causing acute pharyngitis and are indistinguishable clinically.
  4. Throat swab for strep antigen should dictate your therapeutic strategy.
  5. Therapy of strep throat prevents rheumatic fever.

Exanthems

Fungal Infections

Gas Gangrene

GI Bleed

  1. Classified as acute bleed and chronic bleed.
  2. Acute bleed can be either due to upper GI lesions or lower GI lesions.
  3. Melena (black tarry stools) is due to acute upper GI bleeding, above the ligament of Treitz.
  4. Acute lower GI bleed presents as hematochezia.
  5. Chronic bleed presents as iron deficiency anemia.
  6. Postural hypotension is indicative of loss of at least 20% of circulating blood volume or in excess of 1000 cc.
  7. Interpretation of the possible returns from nasogastric tube: Coffee grounds = slow bleeding or oozing. Red blood/clots = active ongoing bleed. Bile stained = no active bleeding above the Treitz ligament. A bile stained NG aspirate would make active bleeding proximal to the third portion of the duodenum most unlikely. Clear = GI bleeding is often times intermittent and can stop spontaneously. The clear return suggests a competent pylorus and bleeding could be still occurring in the bulb and going post bulbar.
  8. Once the patient has stabilized (no orthostasis, slowed pulse) an upper GI endoscopy (EGD) would be the procedure of choice. EGD is diagnostic and can be therapeutic if active bleeding or visible vessels are seen. Injection therapy with epinephrine or a variety of electrocoagulation techniques can be used to stop bleeding. EGD would rule out varices (a cause of severe UGI hemorrhages). Also the EGD could permit a biopsy to evaluate for Helicobacter pylori, a causative agent in most peptic diseases. A biopsy would be taken from an area of the antrum, not from or in close vicinity to bleeding lesions.
  9. Colonoscopy is the procedure of choice for lower GI bleed.

GI Tract Infections

  1. Treatment of Helicobacter pylori is either "triple" therapy with bismuth, metronidazole and tetracycline or newer regimens containing omeprazole and either amoxicillin or clarithromycin.

HIV

  1. CD4 count less than 200 is associated with opportunistic infections.
  2. Common opportunistic infections are PCP, CMV, Tuberculosis, MAC, Cryptosporidiosis, Toxoplasmosis and Candida.

Hyponatremia

Infection

  1. When there is suppression of cell mediated immunity (cyclosporine, azathioprine and prednisone; azathioprine, cyclosporine and glucocorticoids) the ability of macrophages to ingest and kill intracellular pathogens is impaired.
  2. Neutropenia is the major risk factor for pseudomonas infection.
  3. Increasing incidence of infection with Nocardia. Follows increase in organ transplantation and the attendant immunosuppressive therapy.
  4. Criteria for sepsis are: Clinical evidence of infection plus evidence of a systemic response to infection which is manifested by two or more of the following conditions:
    1. Temp > 38ºC or < 36ºC
    2. HR > 90/min
    3. Respiration > 20 breaths/min or PaCO2 < 32mm Hg
    4. WBC >12,000 cells/mm3, < 4000 cells/mm3 or > 10% immature (band) forms
  5. Cold as the initial starting event: Viral infection
  6. Shaking chills and fever? Bacterial infection

Jaundice

  1. Alcoholic hepatitis is characterized by cholestatic picture. AST greater than ALT. AST/ALT ratio > 1, leukocytosis and worsening clinical picture after hospitalization.
  2. Viral hepatitis is characterized by AST is greater than ALT. Transaminases are high. Increased WBC is not typical for viral hepatitis.
  3. Acetaminophen (Tylenol) in therapeutic doses can be and is reported to be toxic in patients with liver disease due to increased P-450 enzyme activity. Tylenol should be used cautiously or probably not at all in these patients and they should be properly instructed about the potential toxicity of therapeutic doses of Tylenol.

Meningitis

  1. Acute meningitis is almost always bacterial.
  2. Initiate antibiotic therapy within 30 minutes of initial encounter. Do spinal tap before initiating therapy.

Myocardial Infarction

  1. WHO definition for Acute Myocardial Infarction: Clinical history of ischemic type discomfort, rise and fall in serum cardiac markers and changes on serially obtained ECG's .
  2. You should understand the need for obtaining sequential cardiac enzymes and EKG and learn to interpret them based on the latency between onset of pain and the time of evaluation.

Our job is to abort the infarct. Decide (with Cardiology consultation) on the method of reperfusion and "Just do it".

Neurocysticercosis

  1. Multiple cystic and calcified lesions on CT scan are strongly suggestive of neurocysticercosis.
  2. Multiple intracranial lesions that enhance with contrast are seen in toxoplasmosis, CNS lymphoma, nocardia, bacterial seeding with endocarditis, and metastatic cancer.
  3. Granulomas caused by tuberculosis and histoplasmosis will calcify, but are rarely multiple.

Pituitary & Adrenal

  1. High resolution MRI of sella turcica with and without gadolinium enhancement is the best imaging procedure when space occupying lesion of pituitary/hypothalamus is suspected.
  2. Presentation of acute onset of polyuria is characteristic of Diabetes Insipidus.
  3. Suppression tests are indicated when there is hyperfunction, stimulation tests are indicated in hypofunctional states.

Pneumonia

  1. Community acquired and hospital acquired pneumonia: Oropharyngeal colonization is different in the community and hospital setting. This makes a difference in the etiology of pneumonia.
  2. The most common organisms in community-acquired pneumonia are Streptococcus pneumoniae (30%), Hemophilus influenzae (10%), Mycoplasma pneumoniae (10%), Chlamydia pneumoniae (8%), influenza virus (7%), and Legionella species (3%). In up to 40% cases, no pathogen is identified.
  3. Pneumococcal vaccine is once in five years is recommended for individuals with chronic pulmonary or cardiovascular disease, diabetes, alcoholism, cirrhosis, chronic renal insufficiency, CSF leak and everyone over the age of 65. In addition, immunocompromised patients with lymphoma, Hodgkin's, myeloma, organ transplantation, splenic dysfunction and HIV infection should be vaccinated.


Renal Failure

  1. Major functions of kidney are Excretion of waste products and drugs, Maintain intra vascular volume, maintain plasma osmolality, maintain acid base status, control blood pressure, maintain electrolyte balance and maintain hemoglobin.
  2. Rule out obstruction as the etiology of acute renal failure. Ultrasound evaluation of kidney helps in this regard.
  3. Pre-renal azotemia and acute tubular necrosis (ATN) are two major considerations for acute renal failure after ruling out obstruction.
  4. Fractional excretion of sodium, BUN/creatinine ratio and specific gravity are most useful to distinguish pre-renal from acute tubular necrosis.Fractional excretion of sodium (FeNa) <1% is pre renal, kidney is trying to conserve sodium to compensate for renal hypo perfusion
  5. BUN/Creatinine ratio >20 is pre renal azotemia
  6. Small kidneys with echogenicty on ultrasound are suggestive of chronic medical renal disease.
  7. Diabetes, Hypertension and Glomerulonephritis accounts for 75% of patients with chronic renal failuure
  8. Protein and red cell casts in urine places the lesion in glomerulus
  9. Acute onset of high blood pressure plus periorbital edema = renal disease
  10. Urinary protein and red cell casts indicate gomerular disease
  11. Body defends cell size than osmolality
  12. Osmolality is the same intra cellular and extra cellular because of free water permeability across cell membrane.
  13. Cells maintain size by changing solute content
  14. Anemia, osteo dystrophy and contracted echogencic kidneys on ultrasound suggests chronic renal disease
  15. Always differentiate renal disease into pre renal, renal and post renal obstructive
  16. Kidney defends volume by manipulating sodium
  17. Kidney maintains osmolality by modulating  ADH and water re absorption
  18. High/low specific gravity, high/low osmolality of urine indicates that kidney has concentrating and diluting ability and the kidneys are normal.
  19. Specific gravity of 1010 (fixed) could mean that kidney has lost its ability to concentrate or dilute urine and is abnormal
  20. Problems in kidney could originate from glomeruli, tubules, interstitium or vasculature
  21. Postural hypotension is indicative of decreased circulatory hypovolemia as in bleeding, dehydration or as due to decreased peripheral vascular resistance as in CHF, Cirrhosis and nephrotic syndrome.
  22. Hyponatremia associated with edema indicates that total body sodium is elevated.

Respiratory Viral Infections

Staph & Strep

  1. WBC features of bacterial infection are: Leucocytosis, shift to left, toxic granules, cytoplasmic vacuoles, Doehle bodies: discrete round or oval density in the periphery of cytoplasm. Stains sky blue with Romanowsky stain and disappearance of eosinophils .
  2. Toxic shock syndromes characterized by low blood pressure, GI symptoms and erythematous rash.
  3. Common causes for Pharyngitis are: viruses and Streptococcus pyogenes.

STD

  1. GC is often associated with Chlamydia and treat for both at the same time.
  2. Look for other STD's when you diagnose one.

Thyroid Disease

  1. Train yourself to suspect endocrine diseases by the first look of the patient. Symptoms are vague and non-specific.
  2. Thyrotoxic patients (after therapy) should be followed annually to make sure that they do not become hypothyroid.
  3. In a patient with hypothyroidism evaluate for coronary artery disease and coexistent hypoadrenalism. Treat adrenal insufficiency first. If the patient has risk factors for CAD, start with very small doses of thyroid and gradually increase the dose weekly.
  4. Clinical picture, TSH and T4 and status of thyroid gland on physical exam are most important in diagnosing the etiology of thyroid dysfunction.

Tuberculosis

  1. Four drugs (Isoniazid, Rifampin, Ethambutol and Pyrazinamide) for three months, followed by INH and Rifampin for six months.
  2. Infection with M. Tuberculosis, not necessarily disease.
  3. Positive skin test reflects cellular memory of the infection.
  4. Measures delayed hypersensitivity to purified protein derivative (PPD).

Viral GI Tract Infection

Meningitis

  1. Fever + change of mental status = Rule out meningitis.

  2. In the setting of meningitis, what will you note in the CSF?

  3. High protein and Leucocytes. Consider bacterial meningitis with low sugar and polys. Consider Viral mengitis with normal sugar and lymphoctes.

  4. Conditions giving low CSF sugar:

  5. Bacteria, Tuberculosis, Fungi, Malignancy

  6. Conditions giving CSF lymphocytosis:

  7. Virus, Tuberculosis, Fungi, Listeria, Malignancy

  8. Meningitis and AIDS? Think cryptococcus (yeast) infection.

  9. Why do patients with chronic bronchitis cough all morning? Mucociliary escalator system dead with accumulation of secretions overnight.

Physical Examination

  1. What causes hypothermia? Shock. Cold exposure. (Typhoid?)

  2. Common causes for sinus bradycardia: Great athlete, Digitalis, Beta-blockers, Myxoedema, Aortic stenosis, Raised intracranial tension

  3. Contraction of scalene muscles with quiet breathing should be checked to assess use of accessory muscles of breathing.

  4. Postural hyotension: Consider Hypovolemia and autonomic dysfunction. Common causes for hypovolemia: blood loss, vomiting, diarrhea, Diabetic keto acidosis.

  5. Common causes for autonomic dysfunction: Diabetes mellitus, ganglion blocking drugs.

  6. How to distinguish postural hypotension due to hypovolemic from autonomic dysfunction? Pulse rate does not go up with autonomic dysfunction.

  7. If S2 split is louder over pulmonic area than S1, you have pulmonary hypertension.

  8. Causes of edema:Pitting: CHF, DVT, hypoalbuminemia/malnutrition

  9. Non-pitting: Filariasis, Thyroid –pretibial myxoedeama, Lymphatic obstruction

  10. Causes of clubbing of nails in pulmonary diseases: Intra thoracic malignancy (primary and secondary), Suppurative lung disease (abscesses, CF, bronchiectasis, empyema), Interstitial lung disease (alveoli/capillary block).

  11. Central Cyanosis: Tongue and conjunctiva blue. Low PO2. Warm hands.MI, pulmonary interstitial fibrosis, hypoventilation, polycythemia, COPD

  12. Peripheral: Lips, nose and fingers bue. Noramal conjunctiva and tongue. Normal PO2. Heart failure (prolonged circulation time), Cold, Raynauds, , DVT

Drugs that cause interstitial lung disease: amioderone, Au+

Causes of ARDS: Sepsis, trauma/burns, gastric aspiration, acute pancreatitis

Your patient developed food poisoning overnight.. It has to be exotoxin-releasing bug in order to cause such a quick reaction. Think Clostridium, staph aureus, listeria?