PCM Spring Exam Material

Anemia
General Approaches to Anemia- Hematocrit < 41% in males, <37% in females
Iron Deficiency Anemia
Essentials of Diagnosis:
Both pathognomonic; absent bone marrow iron stores or serum ferritin < 12ug/L
Caused by bleeding in adults unless proved otherwise
Response to iron therapy
General Considerations: Causes- Deficient iron, decreased absorption, increased requirements (Pregnancy, lactation), blood loss (GI, menstrual, donation), hemoglobinuria, iron sequestration (pulmonary hemosiderosis)
Clinical Findings
S/S:
Easily fatigability, tachycardia, palpitations and tachypnea on exertion
Severe deficiency: Skin and mucosal changes (smooth tongue, brittle nails, and cheilosis)
Dysphagia: formation of esophageal webs (Plummer-Vinson syndrome)
Pica: craving for specific foods- ice chips, lettuce, etc
Labs:
Hypochromic microcytic cells on smear
Low serum ferritin <30ug/L
Increase in total iron binding capacity
Differential Diagnosis
Anemia of chronic disease: Normal or ↑ iron stores, normal or ↑ ferritin levels, serum iron is low, TIBC is low or normal
Thalassemia: Family hx., microcytosis
Sideroblastic anemia
Treatment
Iron replacement: Oral or parenteral iron
ID cause
Anemia of Chronic Disease
Clinical Findings:
Patient with known chronic disease
Low serum iron, low TIBC, and normal or increased serum ferritin
If severe: Suspect co-existing Fe deficiency or folic acid deficiency
Labs: Normal MCV, Normal blood smear
Treatment:
Usually none
Combinant erythropoietin
Vitamin B12 Deficiency
Essentials of Diagnosis:
Macrocytic anemia
Macro-ovalocytes and hypersegmented PMN on peripheral smear
Serum vit B12 levels < 100pg/mL
General Considerations: Causes- Dietary deficiency (RARE-see only in vegans), Decreased production of IF (pernicious anemia, gastrectomy), H. pylori infection, competition for vit. B12 in gut (Blind loop syndrome, fish tapeworm-rare), Pancreatic insufficiency, Decreased ileal absorption of vit. B12 (Surgical resection, Crohn’s), Transcobalamin II deficiency (rare)
Clinical Findings:
S/S:
Glossitis, anorexia, diarrhea,
Complex neurological syndrome (peripheral neuropathy, impairment of posterior columns, difficulty with balance), dementia, decreased vibration and position sense
Pale, mildly icteric
Labs: Megaloblastic anemia, hematocrits as low as 10-15%
DDx: Folic acid deficiency, myelodysplasia, nonhematologic pernicious anemia
Treatment: Parenteral therapy- IM injection of vit. B12; oral cobalamin
Folic Acid Deficiency
Essentials of Diagnosis:
Macrocytic anemia
Macro-ovalocytes and hypersegmental PMN on peripheral smear
Normal serum vit. B12 levels
Reduced folate levels in RBC of serum
General Considerations: Causes- Dietary deficiency, decreased absorption (Tropical sprue, drugs), increased requirement (chronic hemolytic anemia, pregnancy, exfoliative skin disease), loss (dialysis), inhibition of reduction to active form (MTX)
Clinical Findings
Similar to vit. B12- NO neurological changes
Megaloblastic anemia
Megaloblastic changes in mucosa
DDx: Vit. B12 deficiency, Alcoholic (anemia of liver disease), hypothyroidism
Treatment: Folic acid
Hemolytic Anemia
Sickle Cell Anemia and related syndromes
Essentials of diagnosis:
Irreversibly sickled cells on peripheral blood smear
Positive family history and lifelong history of hemolytic anemia
Recurrent painful episodes
Hemoglobin S is the major hemoglobin seen on electrophoresis
Clinical Findings:
Chronic hemolytic anemia: jaundice, pigment gallstones, splenomegaly-initially, and poorly healing ulcers over lower tibia
Enlarged heart: hyperdynamic precordium and systolic murmurs
Hemolytic crisis- splenic sequestration
Aplastic crisis
Vaso-occlusive crisis: acute painful episodes with low-grade fever, provoked by infection, dehydration, or hypoxia; last hours to days
Prone to delayed puberty
Prone to infections: hyposplenism
Labs: Peripheral blood smear, CBC, hematocrit, Sickledex
Treatment: Folic acid supplements, transfusion for crisis, treat precipitating conditions, kept well hydrated and oxygenated; Hydroxyurea for vaso-occlusive crisises
Aplastic Anemia
Essentials of Diagnosis
Pancytopenia
No abnormal cells seen
Hypocellular bone marrow
Genral Considerations: Causes- Congenital (rare), Idiopathic, SLE, Chemo, radiation, Toxins (benzene, toluene, insecticides), drugs, posthepatitis, pregnancy, paroxysmal nocturnal hemoglobinuria
Clinical Findings:
S/S:
Bone marrow failure  weakness, fatigue, neutropenia (bacterial infections), thrombocytopenia (mucosal and skin bleeds)
PE: Pallor, purpura, petechiae
NOT present: Hepatosplenomegaly, lymphadenopathy, or bone tenderness
Labs: CBC, blood smear, bone marrow aspirate
DDx: Myelodysplatic disorders or acute leukemia
Treatment: Supportive care, RBC and platelet transfusion, antibiotics for infections, BMT, If BMT is not possible: immunosuppression with antithymocyte globulin plus cyclosporine
Geriatric SKIP
Kidney Disease
Glomerulonephritis 872-873
Essentials of Diagnosis
Hematuria, dysmorphic red cells, red cell casts, and mild proteinuria
Dependent edema and hypertension
Acute renal insufficiency
General Considerations: Uncommon cause of acute renal failure
Clinical Findings
HTN, edema (first peri-orbital and scrotal), abnormal sediment
Labs: Hematuria, moderate proteinuria, cellular elements
Treatment: Depends on severity: high dose CST and cytotoxic agests; plasma exchange for Goodpasture’s
Nephritic Syndrome
Essentials of Diagnosis
Edema
HTN
Hematuria (w/ or w/o dysmorphic red cells, red cell casts)
General Considerations: Rapidly progressive acute GN can cause permanent damage to glomeruli
Clinical Findings:
S/S: Edema (first peri-orbital and scrotal), HTN (due to volume overload)
Labs: Serum: Complement levels, ANA, cryoglobulins, hepatitis panels, ANCA, anti-GBM ab, ASO titers, and C3 nephritic factors; Urinalysis; Biopsy
Treatment: Reduce HTN and fluid overload; therapeutic management of underlying cause; Salt and water restriction, diuretic therapy, dialysis if needed; may require CST and cytotoxic agents
Hypertension
Management of Hypertension
Etiologies and Classifications
Primary (85%): Onset between 25-55 yo; early in course BP fluctuates
Classification:
Optimal: <120/<80
Normal: <130/<85
High-normal: 130-139/85-90
HTN Stage 1: 140-159/90-99
HTN Stage 2: 160-179/100-109
HTN Stage 3: >180/>110
Factors involved in pathogenesis: genetics, hyperactive sympathetic NS, renin-angiotension system, defect in natriuresis, intracellular Na and Ca (both increased)
Risk factors: obesity, sodium intake, alcohol, smoking, exercise, polycythemia, NSAID (increase), potassium intake (low intake associated with higher BP)
Secondary
Estrogen use
Renal Disease
Renal vascular HTN
Primary hyperaldosteronism and Cushing’s
Pheochromocytoma
Coarctation of the aorta
HTN associated with pregnancy
Complications of untreated HTN (due to sustained elevated BP  changes in vasculature and heart)
HTN cardiovascular disease
HTN cerebrovascular disease and dementia (stroke)
HTN renal disease
Aortic dissection
Atherosclerotic complication
Clinical Findings: Asymptomatic
HA: suboccipital pulsating HA that are worse in the morning
Accelerated HTN: somnolence, confusion, visual disturbances, nausea and vomiting
Pheochromocytoma: Sustained HTN or episodic HTN; attacks of anxiety, palpitations, profuse perspiration, pallor, tremor, nausea and vomiting; markedly elevated BP; angina and acute pulmonary edema may occur
Primary aldosteronism: Muscular weakness, polyuria, and nocturia due to hypokalemia; malignant HTN is RARE; chronic HTN  ventricular hypertrophy; exertional and paroxysmal nocturnal dyspnea
Cerebral involvement: Stroke due to thrombosis or small or large hemorrhage from microaneurysms; HTN encephalopathy
Signs:
BP – take in both arms and lower extremities if pulse is absent, orthostatic
Retinas: Narrowing of arterial diameter, exudates, hemorrhages, or papilledema
Heart and arteries: Systolic ejection murmurs from calcified aortic sclerosis
Pulses: Compare upper and lower extremities
Nonpharmacologic Therapy
DASH diet, weight reduction, reduce alcohol, reduce salt, gradual increase in exercise, smoking cessation
Who should be treated with medication
Patients in stage II or III
Patients that are high normal or stage I are treated with drugs if they have certain risk factors
Goals of Treatment: Reduce cardiovascular risk and further complications
Drug Therapy
Diuretic
β-adrenergic blocking agents
ACE inhibitors
ARB’s
Calcium channel blockers
α-adrenergic receptor blockers
Drugs with central sympatholytic action
Arteriolar dilators
Peripheral sympathetic inhibitors
Hyponatremia and Hypernatremia
Approach to the Patient:
Volume overload: Increased weight, peripheral edema, ascites
Volume depletion: Weight loss, excessive thirst, dry mucous membranes
Dehydration: Pure water deficit
Hyponatremia
Essentials of Diagnosis
Extracellular fluid and serum osmolality are important determinants of etiology
Most cases result from water imbalance, not sodium imbalance
Urine sodium:
If > 20 meq/L: Renal salt wasting
If < 10meq/L: Avid sodium retention due to extrarenal Sodium wasting
Isotonic Hyponatremia: Hyperlipidemia and hyperproteinemia  displaces water  Decreased sodium conc. In total plasma volume
Hypertonic Hyponatremia: Seen with hyperglycemia, water drawn from cells into extracellular space when blood glucose is high. Increase in glucose causes drop in sodium.
Hypotonic Hyponatremia: Retention of electrolyte-free water due to impaired excretion
Hypovolemic hypotonic hyponatremia: Renal or extrarenal volume loss ADH excretion  Free water retention
Euvolemic Hypotonic Hyponatremia:
SIADH
Hypothyroidism- not common; water retention
Psychogenic polydispia and beer potomania: Marked excess of free water intake
Idiosyncratic diuretic reaction: Euvolemic patients on diuretics  xs renal sodium loss and water retention
Idiosyncratic ACE inhibitor reactions: Central polydipsia and increased ADH secretion
Endurance exercise hyponatrium: Xs fluid overload and continued ADH secretion
Mineralcorticoid-responsive hyponatremia in elderly
Treatment
Treat underlying cause and Water restriction
Diuretics
Hypertonic saline: NOT usually recommended
Hyponatremia in AIDS: Associated with pneumonia and CNS processes; euvolemic SIADH
Hypernatremia
Essentials of Diagnosis
Occurs most commonly when water intake or water supplementation is inadequate
Urine osmolality helps differentiate renal from nonrenal water loss
Clinical Findings
S/S: Orthostatic hypotension, oliguria are common. Hyperthermia, delirium, and coma with severe hyperosmolality
Labs:
Urine osmolality > 400 mosm/kg – renal water-conserving ability is functioning: Renal vs. non-renal losses
Urine osmolality < 250 mosm/kg – Dilute urine with hypernatremia is characteristic of central and nephrogenic diabetes insipidus
Treatment:
With hypovolemia: Isotonic saline
With Euvolemia: Drink water, 5% dextrose and water IV
With hypervolemia: 5% dextrose in water + loop diuretic
Renal Calculi
Urinary Stone Disease
Clinical Finding: Colic pain, localized to flank, associated with nausea and vomiting (in constant motion), radiate anteriorly over abdomen; if lodged at ureterovesical junction causes urinary urgency and frequency.
Labs: Serum calcium, phosphate, electrolytes, and uric acid. Urinalysis, plain film and renal U/S, spiral CT
Medical Treatment and Prevention
Increased fluid intake
Sleep stone side down
Surgical treatment: Ureteroscopic stone extraction; shock wave lithotripsy – external energy source fragment stone and lets it pass (not good for women of childbearing age)
Benign Prostatic Hyperplasia
Essentials of Diagnosis:
Obstruction or irritative voiding symptoms
May have enlarged prostate on rectal examination
Absence of urinary tract infection, neurologic disorders, stricture disease, prostatic or bladder malignancy
General Consideration: Older men, genetics (?), DHT sensitivity
Clinical Findings:
Obstructive: hesitancy, decreased force and caliber of the stream, sensation of incomplete bladder emptying, double voiding, straining to urinate, and postvoid dribble
Irritative: Urgency, frequency, and nocturia
Questions to ask:
Over last month, how often have you had the sensation of not completely emptying your bladder after finishing urination?
How often have you had to urinate again less than 2 hrs after you finish urinating?
How often have you found you stopped and started again several times when you urinated?
How often have you found it difficult to postpone urination?
How often have you had a weak urine stream?
How often have you had to push or strain to begin urination?
How many times did you most typically get up to urinate from the time you went to bed at night until the time you got up in the morning?
Signs: PE, DRE, and focused neurological exam on all patients, lower abdomen examination (assess fullness of bladder)
Labs: PSA, urinalysis, electrolyte panel
DDx: Prostatic carcinoma, renal insufficiency, UTI, urethral stricture, bladder stone
Treatment: Mild symptoms: Watchful waiting; Absolute surgical indications are refractory urinary retention; MEDS: α-blocker, 5α-Reductase inhibitors, combination therapy, phytotherapy; Surgery: TURP
Menopause
Menopausal Syndrome
Essentials of Diagnosis:
Cessation of menses due to aging or to bilateral oophorectomy
Elevation of FSH and LH levels
Hot flushes and night sweats
Decreased vaginal lubrication; thinned vaginal mucosa with or without dyspareunia
Clinical Findings:
Menstrual cycles become irregular and longer, menopause occurs when menstruation has not occurred for one year;
Hot flushes; vaginal atrophy (decreased introitus, vaginal dryness, pale, smooth vaginal mucosa, small cervix and uterus); osteoporosis
Labs: Elevated serum FSH and LH; Vaginal cytology: Parabasal cell (loss of maturation due to hypoestrinism)
Treatment: Education; vasomotor symptoms: HRT (mention risks); vaginal atrophy: HRT, estradiol vaginal ring, short-term use of estrogen vaginal cream; Osteoporosis: Calcium fortified foods (1000mg per day + vit D)
Primary Amenorrhea- >14 yo, no breast development, height in lowest 3%; or greater than 16 with no menstruation
Etiology:
Hypothalamic-pituitary causes: Low-normal FSH
Hyperandrogenism: Low-normal FSH
Ovarian causes: High FSH; Turners, AI
Pseudohermaphroditism: High LH
Uterine Causes: Normal FSH
Pregnancy: High hCG
Clinical Findings: Hx. and PE
HA or visual field abnormalities implicate a hypothalamic or pituitary tumor;
Signs of pregnancy;
BP abnormalities, acne, and hirsutism should be noted;
Short stature with gonadal dysgenesis indicates Turner’s syndrome;
Olfaction testing for Kallmann’s syndrome;
Obesity and short stature may be a sign of Cushing’s;
Tall stature may be due to eunuchoidism or gigantism;
Hirsutism or virilization suggest excessive testosterone;
external pelvic exam – assess hymenal patency and presence of uterus
LABS: Serum FSH, LH, PRL, testosterone, TSH, free T4, and hCG
Treatment: Directed at the underlying cause
Secondary Amenorrhea and Menopause
Etiology:
Pregnancy: High hCG
Hypothalamic-Pituitary Cause: Low-normal FSH
Hyperandrogenism: Low-normal FSH
Uterine Causes: Normal FSH
Premature Ovarian Failure: High FSH
Menopause: High FSH
Clinical Findings: Hx and PE
Nausea and breast engorgement: pregnancy
Hot flushes: Ovarian failure
HA or visual field abnormalities: Pituitary or hypothalamic tumor
Thirst, polyuria: diabetes insipidus  hypothalamic lesion
Goiter: Hyperthyroidism
Weight loss, diarrhea, or skin darkening: Adrenal insufficiency
Weight loss and distorted body image: Anorexia
Galactorrhea: hyperprolactenemia
Hirsutism or virilization suggest excessive testosterone
Hypercortisolism: Alcohol or Cushings
Acromegaly, gigantism: pituitary tumor
Systemic illness, drugs
Pelvic exam: uterine and adnexal enlargement, PAP, vaginal smear
LABS: Serum hCG, testosterone, PRL, FSH, LH, TSH, plasma K; renal and liver panel
Treatment: Directed at cause. HRT can relieve symptoms. If labs are normal and not pregnant: 10d course of progestin
Diabetes
Essentials of Diagnosis:

TYPE 1 DIABETES

Polyuria, polydispia, and weight loss associated with random plasma glucose > 200 mg/dl
Plasma glucose of 126 mg/dl or higher after an overnight fast, documented on more than one occasion
Ketonemia, ketonuria, or both

TYPE 2 DIABETES

Most patients are over 40 yo and obese
Polyuria and polydipsia. Ketonuria and weight loss generally are uncommon at time of diagnosis. Candidal vaginitis in women may be an initial manifestation. Many patients have few or no symptoms
Plasma glucose of 126 mg/dl or higher after an overnight fast on more than one occasion. After 75 g oral glucose, diagnostic values are 200 mg/dl or more 2 hrs after oral glucose.
HTN, dyslipidemia, and atherosclerosis are often associated

Clinical Findings:

Type 1 Diabetes / Type 2 Diabetes
Polyuria and thirst / ++ / +
Weakness or fatigue / ++ / +
Polyphagia with weight loss / ++ / -
Recurrent blurred vision / + / ++
Vulvovaginitis or pruritus / + / ++
Peripheral neuropathy / + / ++
Nocturnal enuresis / ++ / -
Often asymptomatic / - / ++

Labs:
Urinalysis: Glucosuria, ketonuria
Blood testing procedures: Glucose tolerance test, glycated hgb, serum fructosamine, self-monitoring of blood glucose, continuous glucose monitoring system, lipoprotein abnormalities in diabetes
DDx.: Hyperglycemia secondary to other causes (Cushing’s, CST, acromengaly, liver disease, muscle disorders…); Non-diabetic glycosuria
Goals of Treatment: Pt. ed, restore known metabolic derangements toward normal in order to prevent and delay progression of diabetic complications
Treatment: Pt. ed, diet, oral agents, insulin

Diseases of the Thyroid
Tests of Thyroid Function: TSH (most sensitive), free T4; thyroid radioactive iodine uptake and scan
Hypothyroidism and Myxedema
Essentials of Diagnosis
Weakness, fatigue, cold intolerance, constipation, weight change, depression, menorrhagia, hoarseness
Dry skin, bradycardia, delayed return of deep tendon reflexes
Anemia, hyponatremia
T4 and radioiodine uptake usually low
TSH elevated in primary hypothyroidism
Clinical Findings:
Early: Fatigue, lethargy, weakness, arthralgias or myalgias, muscle cramps, cold intolerance, constipation, dry skin, HA, and menorrhagia PE: Thin, brittle nails, thinning of hair, and pallor, poor mucosa turgor, decreased return of deep tendon reflexes
Late: Slow speech, absence of sweating, constipation, peripheral edema, pallor, hoarseness, decreased sense of taste and smell, muscle cramps, aches and pains, dyspnea, weight changes, diminished auditory acuity PE: goiter, puffiness of face, carotenemic skin color, thinning of outer eyebrows, thickening of tongue, hard pitting edema, effusions
Labs: Free T4: normal to low; TSH: increased in primary, low or normal in pituitary insufficiency; Lipid panel (increased cholesterol), increased liver enzymes, CK…
DDx: Unexplained heart failure, primary amyloidosis, pernicious anemia, depression
Complications: Mostly cardiac (advanced CAD), megacolon, increased susceptibility to infection, organic psychoses, rarely causes infertility, miscarriage, can progress to myxedema coma
Treatment: Thyroid replacement therapy, usually T4; reassess T4 levels regularly
Hyperthyrodism
Essentials of Diagnosis
Sweating, weight loss or gain, anxiety, loose stools, heat intolerance, irritability, fatigue, weakness, menstrual irregularities
Tachycardia; warm, moist skin; stare; tremor
In Grave’s disease: goiter, ophthalmopathy
Suppressed TSH in primary hyperthyroidism; increased T4, free T4 and free T4 index
General Considerations: Grave’s disease, Toxic adenomas, subacute thyroiditis, jodbasedow disease (iodine-induced hyperthyroidism), thyrotoxicosis factitia, struma ovarii, pituitary tumor, hashimoto’s thyroiditis, pregnancy and trophoblastic tumors, thyroid carcinoma, amiodarone-induced thyrotoxicosis
Clinical Findings: SEE Essentials of Diagnosis; LABS: T4 an TSH levels, serum TSH receptor antibody, serum ANA and anti-dsDNA, sedimentation rate, thyroid radioactive iodine uptake and scan
DDx: Anxiety, mania, acute psychiatric disorder, cardiac disease, hypermetabolism (pheochromocytoma), diabetes, Addison’s
Complications: Cardiac complication, periodic paralysis w/ exercise or heavy carb intake, hypercalcemia, osteoporosis, and nephrocalcinosis
Treatment: Depends on cause
Graves: Propanol for sympathetic relief, thiouria drug, methimazole, propylthiouracil, iodinated contrast agents, radioactive iodine (destroys active thyroid tissue)- not to pregnant women
Metabolic Bone Disease
Osteoporosis
Essentials of Diagnosis
Asymptomatic to severe backache from vertebral fractures
Spontaneous fractures often discovered incidentally on radiography; loss of height
Serum parathyroid hormone, 25(OH)D2, Ca, phosphorous, and alkaline phosphatase usually normal
Demineralization, esp. of spine, hip, and plevis
Etiology
Hormonal deficiency: Estrogen, androgen
Hormonal Excess: Glucocorticoid, thyrotoxicosis, hyperparathyroidism
Immobilization, microgravity
Tobacco, Alcoholism
Malignancy, esp multiple myeloma
Meds: xs.