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Transcript
Spring 2015 exam 1
OMSI CLIs
Mosby’s
Recognize that BUN is related to ammonia levels
Ammonia
Note: humans don’t have urease
Elevated Values: cause encephalopathy and coma; values are usually
taken from venous samples even though arterial values are more
reliable
• Supports Dx of severe liver dz (fulminant hepatitis, cirrhosis); followup of hepatic encephalopathy
• Byproduct of protein catabolism, made by gut bacteria
• Under normal circumstances, goes through the Urea cycle in the liver
and on to be excreted in the kidneys-> cannot be catabolized in
severe hepatocellular dysfx/portal htn
•
•
•
•
Congenital defects in the urea cycle
Impaired renal function
Hemolysis (RBCs have 3 x the amount of ammonia as plasma)
GI bleeding
•
Muscular exertion, cigarette smoking, tourniquet
Decreased levels in essential/malignant htn and hyperornithinemia . We clinically only care about high levels.
Serum amylase p. 60-62
•
Amylase is an enzyme produced in the pancreas and by the salivary glands that converts starches,
glycogens, and related polysaccharides into simple and easily digested sugar.
•
The test is primarily used, in conjunction with a lipase test, to help diagnose and monitor acute
pancreatitis and other pancreatic disorders.
Ordered frequently to:
•
•
•
Detect and monitor the clinical course of pancreatitis
When a patient presents with acute abdominal pain
Test explanation
•
Sensitive but not most specific for pancreatitis
•
•
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•
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•
Damage to acinar or obstruction of duct by carcinoma or gallstones causes outpouring into
intrapancreatic lymph and free peritoneum
Abnormal levels rise within 12 hours of the onset of the disease
It is rapidly excreted by kidneys
Persistence = pathology
Non-pancreatic diseases that can elevate:
•
•
Amylase is normally secreted from pancreatic acinar cells into pancreatic duct and into duodenum
Aids in the digestion of carbs
Can be elevated for bowel perforation, penetrating peptic ulcer, duodenal obstruction, salivary gland
infection, ectopic pregnancies, severe diabetic ketoacidosis
Patients with chronic pancreatic necrosis due to tumor or massive hemorrhage may cause low
amylase levels
Serum amylase
•
Interfering factors
•
•
•
Serum lipidemia factitiously decreases amylase
IV dextrose lowers amylase
Aminosalicylic acid, aspirin, azathioprine, corticosteroids, dexamethasone, ethyl alcohol, glucocorticoids, iodine
containing contrast medium, loop diuretics, methyldopa, narcotic analgesics, oral contraceptives, prednisone
• Increased levels
•
•
•
•
•
•
•
•
•
Acute pancreatitis, chronic relapsing pancreatitis, penetrating
peptic ulcer into the pancreas
GI disease
Acute cholecystitis
Parotiditis (mumps)
Ruptured ectopic pregnancy
Renal failure
Diabetic ketoacidosis
Pulmonary infarction
After endoscopic retrograde pancreatography
Antinuclear antibody (ANA) p. 9092
• Used to diagnose systemic lupus erthematosus (SLE) and
other autoimmune disease
•
•
•
•
•
•
Drug-induced SLE
Scleroderma
Rheumatoid Arthritis
Sjogren syndrome
Dermatomyotosis
Polyarteritis
• ANA is a group of protein antibodies that react against cellular
nuclear material
• Normal findings negative at 1:40 dilution.
• Used to rule out SLE, negative results probably not SLE.
Erythrocyte sedimentation rate
(ESR) p. 234-235
• Non-specific test used to detect illnesses associated with acute and
chronic infection, inflammation, advanced neoplasm, and tissue
necrosis or infarction
• Routine test for patient with vague symptoms
• ESR lags behind other indicators early in an infection. May stay
elevated longer in the convalescent stage of a disease or infection.
• Especially helpful for inflammatory autoimmune disease
• Measure rate at which RBC settle in saline solution or plasma per
unity time
• RBC will settle faster with illness due to increased plasma proteins
(fibrogen)
• Westergren Method
•
•
•
•
Male up to 15 mm/hr
Female up to 20 mm/hr
Child up to 10 mm/hr
New born 0-2 mm/hr
GGT p. 259-260
•
•
Sensitive to hepatobiliary disease, also an indicator of heavy and
chronic alcohol use
Test explanation
•
•
•
•
•
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•
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•
•
Enzyme participates in the transfer of amino acids and peptides across the
cell membrane
Highest concentrations found in liver and biliary tract
Smaller concentrations found in kidney, spleen, heart, intestine, brain, and
prostate gland
Detect liver cell dysfunction highly accurate in indicating even slightest
degree of cholestasis
Detects biliary obstruction, cholangitis, or cholecystitis
Parallels elevation of ALP but more sensitive
Not increased in bone disease
Elevated in 75% of patients that chronically drink
Elevated with MI
Interfering factors
•
•
•
May decrease late in pregnancy
Drugs that increase: alcohol, phenobarbitol, and phenytoin
Drugs that decrease: clofibrate and oral contraceptives
Gliadin antibodies
Anti-gliadin IgA/IgG; Anti-endomysium IgA; Antitissue transglutaminase IgA p. 263-265
• Endomysial IgA, gliadin IgA, tissue transglutaminase TG-ab
• Diagnose celiac disease and sprue by identifying ab to gliadin
and gluten in affected patients
• Crohn, colitis, and severe lactose intolerance may increase
levels
• Test explanation
Gliadin and Gluten are found in wheat products. Patients
cannot tolerate ingestion of gliadin and gluten which are toxic
to intestinal mucosa
• Patients experience severe malabsorptive symptoms
• Gliadin and gluten cause direct mucosal damage and Ig appear
in gut mucosa and in serum
Lactose tolerance test *
assigned pages wrong
(332-334?)
• Used to diagnose lactose intolerance caused by lactase
insufficiency, intestinal malabsorption, maldigestion, or bacterial
overgrowth in small intestine. In enterogenous diarrhea (lactose
broken down but not absorbed due to damaged gut)
• Test explanation:
•
•
•
•
•
•
Glucose plasma will not rise after the ingestion and the small bowel
is flooded with a high lactose load
Bacterial catabolism occurs in the intestine creates flatus and
hydrogen
Symptoms include flatulence, abdominal cramping, bloating,
diarrhea, and failure to thrive in infants
Lactose load is given and if lactase is absent then the serum
glucose will not rise
Given glucose tolerance test to isolate lack of lactase
Hydrogen Breath test in which expelled air is analyzed for
hydrogen content (goes up) for when bacteria are exposed to
undigested food
Protein
Indications: monitor disease course w/ cancer (lymphoma,
myeloma); intestinal/renal protein wasting states, immune
disorders, liver dysfx, impaired nutrition, edema
• Proteins are the most significant component contributing to
osmotic pressure in the vascular space, minimizing
extravasation of fluid.
• Albumin makes up 60% of total protein; its major effect is to
maintain colloid osmotic pressure and transports drugs,
hormones, and enzymes
• Because albumin is synthesized in the liver, protein levels will
be severely decreased in liver dysfunction-> but the ½ life of
albumin is 12-18 days, so this may not be apparent
immediately
Protein
• Globulins are the building blocks of antibodies, and are not as important in
maintaining osmotic pressure
• A1 globulin = a1 antytripsin*;
• A2 globulins = haptoglobins, ceruloplasmin, prothrombin, and cholinesterse**;
increased in nephrotic syndrome and inflammatory conditions; decreased in
hemolysis, Wilson’s dz, hyperthyroidism, and liver dysfx
• B1 globulins = lipoproteins, transferrin, plasminogen; increased in
hypercholesterolemia and iron-deficiency anemia
• B2 globulins = fibrinogen
• Gamma globulins = immune globulins; increased in multiple myeloma and
Waldenstrom macroglobulenemia, chronic inflammatory conditions, other
malignancies (Hodgkin’s dz, lymphoma, leukemia, cirrhosis, infections); decreased
in genetic conditions and immunodeficiencies
People w/ decreased proteins: malnourished, burn pts, protein losing
enteropathies (nephrotic syndrome), pregnancy, inherited dz
Selective lack of albumin: collagen vascular dz (albumin is a small molecule),
chronic liver dz-> total protein may be normal, but the normal albumin > globolun
ratio of >1 is off
Increased total proteins: multiple myeloma; factious elevations can happen in
dehydration; inflammatory dz
Proteins
• Electrophoresis separates various components of blood via
electrical charge
• Normally patterns specific to immunoglobulins is polyclonal; a
monoclonal spike indicating overproduction of one immunoglobulin-:
suspect allergy or a neoplasm like multiple myeloma
*See Table 2-41 for details
Urine electrophoreses: detection of renal protein-losing nephopathies.
BENCE JONES = MULTIPLE MYELOMA; pts have a monoclonal spike in
Beta or Gamma globulin zone
Lipoid nephrosis causes selective albumin leaks
While there are multiple methods of electrophoresis, the common one
is immunoflication electrophoresis (IFE)
• Monospecific antibody is placed in contact w/ the gel after protein
separation
• Protein-antibody complexes are specifically stained for visualization;
the pts pattern is compared to references
Rheumatoid factor (RF) p. 471472
• Negative <60 units/mL
• Used in the diagnosis of RA
• RA:
•
•
•
•
•
•
morning stiffness for 6 weeks
pain in at least one joint
swelling in at least 1 joint
symmetric bilateral joint swelling,
presence of subcutaneous nodules
radiographic changes
• Abnormal IgG made in synovial joints, act as “antigens”
• IgG and IgM along with Fc attack abnormal IgG
• Immune complexes are activated and joint destruction begins
RF
• Tests mainly for identification of IgM (Reactive IgM and
sometimes IgG and IgA make up Rheumatoid Factor)
• Approximately 80% of pts with RA have positive RF titers
• Must be found in greater than 1:80 dilution
• SLE may also give false positive (dilution usually less than 1:80)
• Other autoimmune dzs, tuberculosis, chronic hepatitis, infectious
mononucleosis and subacute bacterial endocarditis may give
false reading
• Does not disappear in remission, ANA does
• False negatives 20% of time, so negative test not used to rule
out RA.
Free Thyroxine Index p 512513
•
•
•
Evaluate thyroid function
Corrects for changes in thyroid hormone binding serum proteins that can affect T4
Diagnose hypothyroidism and hyperthyroidism esp. in patients with abnormal thyroxinbinding globulin or evaluation during pregnancy (TBGs go up).
• Measures the amount of free thyroxine T4 which is only 1% unbound goes into cells and is
activated
• Not affected by thyroxin-binding globulin (TBG ) abnormalities so it correlates more
closely to hormonal status than total T4 and T3
• If TBG is increased, the T3 uptake decreases and corrects for the increased T4 association
TBG proteins.
• If TBG is normal and T4 is elevated, FT4 will be elevated indicating true hyperthyroidism
• Low FT4 indicates hypothyroidism
Increased levels:
•
•
•
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primary hyperthyroidism,
acute thyroiditis,
factitious hyperthyroidism,
struma ovarii (germ cell ovarian cancer producing thyroid hormone)
Decreased:
•
•
•
•
hypothyroidism,
pituitary insufficiency,
Hypothalamic failure
iodine insufficiency
Total Thyroxine p. 15-516
•
•
Diagnose thyroid function and to monitor replacement and suppressive
therapy
Measures T4, both free and protein bound
•
•
•
T4 is 90% of secreted hormone from thyroid.
Nearly all T3 and T4 are bound by serum proteins (eg TBG, albumin)
TRH (hypothalamus) -> TSH (Pituitary) -> Thyroid hormones
•
•
•
•
•
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TSH stimulates thyroid to secrete thyroid hormone
High levels of hormone inhibit TRH
High levels indicate hyperthyroid, low is hypothyroid
TBG affects results (When T4 is bound it is not metabolically active, so
increased binding causes increased secretion of hormones, without
metabolic abnormalities)
Interfering factors:
•
increased after iodinated contrast x-ray, pregnancy causes increased levels, amphetamines, clofibrate, estrogens,
heroin, iodinated contrast media, iodine, methadone, and oral contraceptives increase
Decrease levels:
•
anabolic steroids, androgens, anti-inflammatory drugs, antithyroid drugs, barbituates, furosemide, nonsteroidal lithium
phenytoin, propranolol, propylthiouracil
Total Thyroxine
High:
• Primary Hyperthyroidism
• Acute thyroiditis,
• Familial dysalbuminemic
hyperthyroxemia*
• factitious hyperthyroidism,
• Struma ovarii,
• TBG increase *
*= difference from Free T4
test
Low:
•
•
•
•
Hypothyroidism
pituitary insufficiency
hypothalamic failure
protein malnutrition and
other protein depleted
states*
• iodine insufficiency
• non-thyroid illness
Uric Acid, blood p. 536-537
• Used to evaluate gout or recurrent urinary calculus (Kidney
stones).
• Test explanation:
• Uric acid is a waste product of purine catabolism, made primarily
by liver.
• 75% of uric acid is excreted by the kidneys, 25% by intestinal tract
• Uric acid is poorly soluble and with elevations (hyperuricemia)
crystals can from in kidney’s or ureters or synovium of joints (esp.
distal lower extremity (Gout). Soft tissue deposition are called
tophi.
• Causes of hyperurcemia can be overproduction (eg tumor lysis
syndrome in chemotherapy, enzyme deficiencies) or decreased
excretion (e.g. kidney failure). Many cases are idiopathic
• Hyperuricemia is defined as a plasma uric acid level greater than
6.8 mg/dL
Uric Acid
Increased
• Increased production
• Increased ingestion of purines (foods
such as liver, breads, kidney, anchovies)
• Genetic inborn error in purine
metabolism
• Metastatic cancer
• Multiple myeloma
• Leukemias
• Cancer Chemotherapy
• Hemolysis
• Rhabdomyolysis
• Decreased excretion
•
•
•
•
•
•
Idiopathic
Chronic renal disease
Acidosis
Hypothyroidism
Alcoholism
Shock or chronic blood volume depletion
states
Decreased
•
•
•
•
Wilsons disease
Faconi syndrome
Lead poisoning
Yellow atrophy of the liver
Vitamin D
• Used in the assessment of postmenopausal women to ensure they
have adequate levels to absorb dietary calcium
• Fat Soluble Vitamin (A,D, E, K)
• Vit D2= ergocalciferol*; vit D3= Ergocalciferol-> from sunlight
• 7-dehydrocholesterol reacts w/ UVB light -> vit D3
• Adequate levels of vit D3 can be achieved in 10-15 mins, 2+
times/week
• Melanin is a light filter in the skin, so dark skinned people need
more time in the sun to get as much vit D
• Vit D2/3 is converted in the liver to 25-hydroxyvitD, then in the
kidney to 1,25 dihydroxyvit D; it is then bound to proteins and
circulates in the plasma
• Hormonally active form binds to the Vit D receptor in the nucleus,
acting as a txn factor to increase the expression of genes like TRVP6
and calbindin, encouraging Ca2+ absorption in the intesting
Vitamin D
• Vit D activation in intestine, bone, kidney and parathyroid gland is
important for Ca and phosphorous dietary absorption
• Vit D inhibits PTH secretion
• Enhances immune responses (phagocytosis etc)
Deficiencies:
• inadequate sunlight, malabsorption (Cystic fibrosis, etc), Liver/Kidney
dysfx, hereditary metabolic d/o-> leads to defective mineralization->
Rickets in kids and Osteomalacia in adults
Other deficiency problems
• Vit D is also thought to be involved in apoptosis-vit D deficiency is observed
in cancers (colon, breast, pancreas)
• +BP, cardiovascular risk
• Immunity-> VDR expressed in monocytes, T/B cells
Optimal levels are 30 ng/Dl-> , higher requirements for darker skinned
people and the elderly (7-dehydrocholesterol converting activity reversed
in the elderly); breast milk does not have vit D; obese people have a
harder time getting vit D into the blood stream
Vit D
• Toxicity: nonspecific (vomiting, poor appetite, confusion,
rhythm abnormalities); associated w/ hypercalcemia
• Increased risk of kidney stones
Drugs that decrease Vit D: steroids, orlistat, cholestyramine
Drugs that increase Vit D: barbituates, phenytoin (inhibit hepatic
metabolism)
Increased levels: Williams syndrome*, excessive dietary
supplements, sarcoidosis
Decreased levels: Rickets/Osteomalacia, Osteoporosis,
Malapsorption, Renal dz, Liver Dz, X-linked hypophosphatemic
rickets, Inflammatory dz, inadequate diet/sun
Electroencephalography
• Indications: identify/evaluate pts with seizures; can detect other
conditions involving brain cortex; confirmatory test for brain death;
evaluation of trauma
• Graphic recording of the electrical activity of the brain
• Seizures: the focus is characterized by rapid, spiking waves
• Cerebral lesions: abnormally slow EEG waves
• Monitors electrophysiological effects of blood flow during surgical
procedures (example: carotid endarterectomy)
• EcoG (electrocroticography): performed during craniotomy;
electrodes are placed directly on the brain to record activity from the
cerebral cortex
• Gold standard for defining epileptogenic zones before surgical
procedures.
• MEG (Magnetoencephalography): noninvasive imaging, measures
manetic fields produced by the brain using a SQUID (superconducting
quantum interference device); help surgeons localize
pathology/identify seizure loci and plan surgical procedures (aka
avoiding critical areas)
Electroencephalography
• Interfering factors: hypoglycemia, caffeine, body/eye movements, lights,
sedatives
• Abnormal results (except when indicated, most of these show slowing of
the EEG): Seizures (increased activity), brain tumor, abscess, intracranial
hemorrhage, infarct, brain death, encephalitis, narcolepsy (sleep waves
seen during waking hours), metabolic encephalopathy
• Criteria for Brain Death (Box 3-4)
• Absence of hypothermia (T> 32.2 C-you’re not dead until you’re warm and
dead)
• Absence of neuromuscular blockade administration
• Ruled out drug/metabolic coma
• No response to noxious/painful stimuli
Confirmatory tests
• Cerebral flow shows no flow to the brain
• Isoelectric EEG (repeat in 6h)
• No attempt at respiration w/ PCO2 >50 mmHg
• Fixed pupils
• Absent corneal reflex
Arthrocentesis p 673-674
• Normal findings:
• Synovial fluid – clear and straw colored with few WBCs, no crystals, and
good mucin clot
• Indications:
• Ddx joint infection, arthritis, crystal-induced arthritis (gout and
pseudogout), synovitis, or neoplasms involving the joint
• Monitor chronic arthritic dzs, inject steroids
• Can be performed on any major joint (examples: knee, shoulder,
hip, elbow, wrist or ankle)
• Adding acetic acid to aspirated joint fluid, should clot
• Poor clot quality in in presence of inflammatory disease.
• If bleeding has occurred into the joint, it may clot spontaneously,
but this is abnormal.
Arthrocentesis p 673-674
• Septic Arthritis:
• Resulting from either penetrating trauma or blood-borne infection (during bacteremia)
• Joint is usually red, warm, swollen, and painful
•
•
Reduced glucose, increased WBCs, increased Protein, Increased lactate.
Gram stain and culture
• Osteoarthritis:
• Non gouty crystals or other degenerative changes can cause chronic and acute flare up.
• Synovitis:
• Inflammatory or infectious
• Neoplasm:
• Protein levels elevated, microcopy may reveal malignant cells
• Joint effusion:
• Fluid in the joint, fluid analyzed to determine source of swelling
• Systemic lupus erythematous, Rheumatoid Arthritis:
• Autoimmune or collagen-vascular dzs can be ass with immunogenic arthritis
•
Reduced complement level, increased WBCs, increased protein
• Gout, pseudogout:
• Cystral-induced arthritis with urate crystals or calcium pyrophosphate crystals are deposited
into joint-surrounding structures and joint surface cartilage.
•
Inflammation (up WBCs in synovial fluid)
• Trauma:
• Joint effusion or bleeding into joint may occur
Quantitative fecal/stool fat p.
893-895
•
•
Confirm diagnosis of steatorrhea, when patient has large, greasy, and
foul-smelling stools
Total output of fecal fat per 24 hours in a 3-day stool collection provides
the most reliable measurements.
•
•
Abnormally high fat content confirms diagnosis
Fat retention coefficient is used in infants and children. Coefficient should be
at least 95%.
Increases in fecal fat:
•
Cystic Fibrosis:
•
•
•
•
•
•
Children with CF have obstructed pancreatic ducts so they cannot be expelled
into the intestine
Any condition that causes malabsorption (sprue, Crohn, Whipple,
gallstones, tumor, duct obstructions)
Short gut: causes higher fecal fat
Enemas and laxatives may increase fat
Barium and fiber laxatives decrease
Increased: CF, malabsorption due to celiac, sprue, whipple, crohn or
radiation enteritis, short gut
Stool for occult blood p. 898901
•
•
Screening for colorectal cancer
Test explanation
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Tumors of the intestine grow into the lumen and are subjected to repeat
trauma by the fecal stream
The friable neovascular tumor ulcerates and bleeds
Guaiac chemistry (most common) performed on the stool to detect blood
peroxidase-like activity of hgb, which catalyzes reaction of peroxide and a
chromogen forming ortholidine, producing a blue color.
OB can be detected by immunochemical methods called fecal
immunochemical test (FIT) or immunochemical fecal occult blood test,
these are not affected by red meats or plants like Guaiac, but may fail to
recognize upper GI blood
DNA stool sample test is twice as sensitive as guaiac for colorectal
precancerous, benign or malignant tumors because some polyps don’t shed
blood
Benign, malignant GI tumors, ulcers, inflammatory bowel disease,
arteriovenous malformations, diverticulosis, hematobilia all cause OB
Also Hemorrhoids and swallowed blood result in OB
Stool hemoccult
•
Interfering factors
•
•
•
•
•
•
Bleeding gums following dental procedure or disease
Animal hemoglobin of ingested animal meat
Peroxidase rich vegetables (turnips, horseradish, artichokes, mushrooms, radishes, broccoli, bean
sprouts, cauliflower, oranges, bananas, cantaloupes, grapes)
Anticoags, aspirin, colchicine, iron, nonsteroidal antiarthritics, and steroids
drugs that instigate peroxidation reaction Boric acid, bromides, colchicine, iodine, iron, rauwolfia
Vitamin C inhibits peroxidation reaction causing false negatives
• Results and significance: Can detect occult blood with as little as
5mL lost per day
•
•
•
•
•
•
•
GI tumor and polyps
Peptic disease (esophagitis, gastritis, and ulceration)
Varices (from portal hypertension)
IBD (Ulcerative colitis, Crohn disease)
Ischemic bowel disease
GI trauma or surgery
Hemorrhoids and other anorectal problems
Urine amylase p. 953-954
• Normal value up to 5000 somogyi units
• Used to assist in making the diagnosis of pancreatitis although
other nonpancreatic diseases can cause elevated urine amylase
levels
• Levels rise later than blood amylase levels
• Several days after the onset of disease serum may be normal but
urine levels are significantly elevated, useful for detecting
pancreatitis late in the disease course
• Test explanation:
•
•
•
•
Kidneys clear amylase, disorders that affect pancreas cause
increased amylase levels in urine
Serum levels rise transiently after resolution of acute phase of
disease, urine levels remain elevated 5-7 days after onset
Not specific for disorders: parotiditis, cholecystitis, perforated
bowel, peptic ulcer, ectopic pregnancy and renal disease
See Serum amylase for test result significance
Barium enema
Detect:
• Malignant tumor – evident as filling defect “apple core” appearance.
• Polyps – round filling defects, however stool can create same effect
• Diverticula – outpouchings. Diverticulitis is inflammation of these defects in the wall and may show narrowing
• Inflammatory bowel disease - evident as narrowing of colon
•
•
•
Ulcerative colitis – may produce cobblestone-like patterns a result of inflammation surrounding the colon (do not
confuse with cobblestone appearance inside lumen seen in Crohn!). Loss of hustra. “Lead pipe appearance “.
•
Crohn disease- areas devoid of contrast are classic finding. Rectum is usually involved in crohn, but spared in
Ulcerative colitis. Fistulas may be evident. “String sign “ = tubular narrowing due to spasm or stricture.
•
•
•
•
•
•
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Colonic stenosis secondary to ischemia – “non-apple core” like narrowing
Perforated colon – leakage of contrast. Most common cause is cancer or diverticulitis (avoid use if perforation is
suspected)
Colonic fistula– leakage to another organ (example : urinary bladder)
Appendicitis- lack of filling, 30%-60% of normal appendixes do not fill.
Extrinsic compression of colon from extracolonic tumor or absecess – convexity
Malrotation of gut- congenital abnormality cecum usually in RLQ, appears in LUQ
Colon Volvulus – cut off of flow
Intussusception – flow of barium stops at the tip of the intussuceptum.
Hernia – seen inside gut lumen outside abdomen
•
Do not use if there is a risk of perforation of the bowels.
Bone Densitometry p 10551057
• Findings:
• Normal = <1 SD below normal
• Osteopenia = 1.0-2.5 SD below normal
• Osteoporosis =
>2.5 SD below normal
• DEXA = Dual Emission X-ray Absorptiometry
• Dual photons used in x-ray spectrum, can measure density of bones
• [THIS WAS A BONUS QUESTION LAST YEAR]
• Important causes of reduced bone density
•
•
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•
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•
•
Postmenopausal women, esp. with early menopause
Hyperparathyroidism
Chronic renal insufficiency (vitamin D is activated in kidney and phosphate levels regulated)
GI malabsorption (Vit D is fat soluble, calcium not absorbed)
Anorexia
Certain cancers
Corticosteroid use longer than 3 months
Certain endocrinopathies (eg Cushing syndrome)
Chronic Heparin therapy
Chronic immobility
Drugs
Drug
Uses
Side effects
Contraindications
Therapeutic
considerations
Alendronate
Class: Bisphosphonate
Mech: Decreases bone
reabsorption by osteoclasts;
blocks a step in the
mevalonate pathway
•
•
Delayed gastric emptying
•
Extended skeletal
effects,
•
•
Cessation of bone
remodeling
Inability to sit up for 30
minutes after taking drug
•
unclear how to
define overdose
Indications:
•
Osteoporosis
prevention and
treatment
•
Paget’s disease
•
Gastroesophageal
pain, ulceration
•
IV dose corrects
hypercalcemia in
days
•
all secreted by kidney
Mech: binds to and
activates a G-protein
coupled receptor on
osteoclasts to decrease
resorptive activity
Indications:
•
Hypercalcemia
•
Paget’s disease
•
Postmenopausal
osteoporosis
•
•
•
•
Class: Selective estrogen
receptor modulator (SERMs)
Mech: Estrogen receptor
agonist in bone,
estrogen receptor
antagonist against
endometrium and breast
Indication:
• Osteoporosis prevention
and treatment
• Retinal vascular
occlusion
• Venous
thromboembolism
• Pulmonary embolism
• Hot flashes
• Leg cramps
Jaw osteonecrosis in
cancer patients
•
Calcitonin
(Salmon)
Raloxifene
Flushing
Nausea
Diarrhea
Tachyphylaxis
Hypocalcemia
Oral formulations require
staying up right, to prevent
esophageal reflux.
• Hypersensitivity
• Nasal spray or
subcutaneous
• Subcutaneous lowers
blood calcium over
hours
• Pregnancy
• History or presence of
venous thromboembolism
• Decreases breast
cancer incidence
• (Currently used for
Prevention; risk
reduction of invasive
breast cancer in
postmenopausal women
at high risk for invasive
breast cancer . )
Drug
Uses
Side effects
Contraindications
Therapeutic considerations
Enalapril
Class: ACE Inhibitors
Mech: Decreases
conversion of angiotensin
(AT) I to AT II, which
decreases
vasoconstriction of
arterioles, aldosterone
synthesis, renal proximal
tubule NaCl reabsorption,
and ADH release; also
inhibits degradation of
bradykinin, which
increases vasodilation
Indications:
• Hypertension
• heart failure
• diabetic nephropathy
• post - MI
• Angioedema (more
•
•
•
•
•
•
frequent in black
patients)
Agranulocytosis
Neutropenia
Cough,
Edema
Hypotension
Rash
Gynecomastia
Hyperkalemia
Proteinuria
• History of
angioedema
• Bilateral renal artery
stenosis
• Renal failure
• Pregnancy (Cat X)
• Ester prodrug activated
in plasma
• Bradykinin causes cough
and edema; angioedema
can be potentially lifethreatening
• Delays progression of
cardiac contractile
dysfunction in HF and
after MI; delay diabetic
neuropathy (Mortality
benefits = EVERYONE
GETS IT unless
contraindicated)
Class: Calcium channel
blocker
Mech: calcium channel
blocker
Indication:
• Exertional angina
• Unstable angina
• Coronary spasm
• Hypertension
• Hypertrophic
cardiomyopathy
• Pre-eclampsia
•
•
•
•
•
•
•
•
Increased angina,
Rare MI
Palpitations
Peripheral edema
Flushing
Constipation
Heartburn
Dizziness
Amlodipine
(Dihydropyridine)
•
•
•
Co-admin with
allopurinol may
predispose to
hypersensitivity rxn
including Steven
Johnson syndrome
• Preexisting
hypotension
• Arteriolar dilation
greater than venous
• High vascular to cardiac
selectivity (see
Verapamil for
comparison)
• Less depression of
myocardial contractility,
minimal effects on nodal
conduction
• Higher bioavailability,
longer time to peak
plasma concentration,
Drug
Uses
Side effects
Contraindications
Therapeutic considerations
Naproxen
Propionic acid
(NSAID)
pseudoporphyria,
See Ibuprofen
•
•
•
Mech: See Ibuprofin
Longer half life,
20x more potent
than ibuprofen,
causes fewer GI
adverse affects
mild to moderate
pain, fever,
osteoarthritis, RA,
dysmenorrhea, gout
Ketorolac
(Brand =
Toradol)
Acetic acid (NSAID)
See Ibuprofen
See Ibuprofen
Analgesia in
postsurgical patients,
used for no more
than 3-5 days
Stomach upset or
pain, constipation,
diarrhea, nausea or
vomiting
Diabetes, infants,
may upset ulcers,
not to be take with
thalassemias, may
irritate IBS
(Clinical pearl: May cause
dark stools, of note clinically
when someone has a
suspected GI bleed. Stools
will not have positive Occult
blood test, if dark from only
iron supplement)
Severe pain
See Ibuprofen
FeSO4
Iron supplement for
anemia due to blood
loss and iron
insufficiency
Drug
Uses
Side effects
Contraindications
Therapeutic considerations
Donepezil
Class:
Acetylcholinesterase
Inhibitor
Diarrhea, nausea,
vomiting, cramps,
anorexia, vivid dreams
Treatment
associated liver
function test
abnormalities
Modest symptomatic
benefits
ACHe inhibitors
Mech: Increases ACh
by blocking breakdown
in synapse
= symptoms of
hyperactive
parasympathetics
Dementia may be linked
to low levels of
Acetylcholine.
Mild to moderate
Alzheimer’s/Dementia
Pantoprazole
Proton pump inhibitor
Same as omeprazole
Same as
omeprazole
Same as omeprazole
Omeprazole
Proton pump inhibitor:
decrease acid secretion by
irreversibly inhibiting H+/K+
ATPase on parietal cells
Peptic ulcer disease, GERD,
erosive esophagitis, gastic
acid hypersecretion
h. Pylori GI tract infection
Given as IV
-erosive esophagitis
-bleeding ulcer
Pancreatitis, hepatotoxicity,
interstitial nephritis, may
affect effects of clopidigrel
increased risk of hip, wrist
and spine fracture, hospital
acquired pneumonia, and
enteric infections including
clostridium difficile,
salmonella, E. coli,
headache, rash, GI
discomfort, diarrhea,
anorexia, asthenia, back pain
hypersensitivity
Proton pump inhibitors
metabolized in liver by
CYP2C19 and CYP3A4 drug
interaction with ketoconazle
or itraconazle due to acid
environment needed to
absorb azole drugs
Drug
Uses
Side effects
Contraindications
Therapeutic considerations
Aluminum
hydroxide
Symptomatic relief of
dyspepsia associated with
peptic ulcer disease, GERD
or hiatal hernia
Phosphate depletion (severe
weakness, malaise anorexia),
constipation, osteomalacia
in patients with renal failure
hypersensitivity
All antacids can potentially
increase or decrease the
rate or extent of absorption
of concurrently administered
oral drugs by changing
transit time or by binding
the drug
Magnesium
hydroxide
Symptomatic relief of
dyspepsia associated with
peptic ulcer disease, GERD
or hiatal hernia
Diarrhea, hypermagnesemia
in patients with renal failure
Hypersensitivity
Same as above
Also used to treat
constipation
Drug
Uses
Side effects
Contraindications
Therapeutic considerations
Levothyroxine
Thyroid Hormone,
T4, for hypothyroidism,
myxedema coma
Replaces missing hormone
Hyperthyroidism,
osteopenia, pseudotumor
cerebri, seizure, myocardial
infarction
Acute MI, uncorrected
adrenal cortical
insufficiency
Untreated
thyrotoxicosis
Cholestyramine and sodium
polystyrene sulfonate
decrease absorption of
synthetic thyroid hormone
Rifampin and phenytoin
increase metabolism
T4 is the more desirable
hormone to replace because
of its longer half life
(compared to T3).
Hydrocortisone
Verapamil
(Phenylalkylamine)
• Corticosteroid
•
Replacement therapy
for primary and
secondary adrenal
insufficiency
•
Reduces inflammation
Cushing syndrome
(iatrogenic) , reduces bone
density with chronic use
Class: Calcium channel blocker
Mech: block voltage-gated Ltype calcium channels &
prevent influx of calcium that
promotes actin-myosin crossbridge formation
Indications:
• Prinzmetal or variant
angina or chronic stable
angina
• Hypertension
• A fib or flutter, paroxysmal
SVT
•
•
•
•
•
•
•
•
Fungal infection
Abrupt discontinuation can
cause adrenal insufficiency
Rare cardiac arrhythmia
AV block
Bradyarrhythmia
Exacerbation of heart failure
Peripheral edema
Syncope
Gingival hyperplasia
Dizziness
Systemic steroids given for
getter than 5-7 days require
tapering the dosage to avoid
adrenal insufficiency.
Hyperglycemia is common in
diabetics due to the counter
regulatory hormonal action
of steroids.
• IV is contraindicated
in patients with
ventricular
tachycardia and
patients receiving IV
beta blockers
• Sick sinus syndrome
or 2nd or 3rd AV block
• SVT associated with
bypass tract
• Left ventricular failure
• Hypotension
• Acute MI
• Low ratio of vascular to
cardiac selectivity
• Depresses both SA and AV
node conduction velocity
• Raises serum
carbamazepine levels which
may cause toxicity
• Avoid using with beta
blockers
• Greater suppressive effect
on cardiac contractility
Drug
Uses
Side effects
Contraindications
Therapeutic considerations
Acetaminophen
Class: NSAID
Mech Weak inhibitor of peripheral
cyclooxygenases; predominant
effect may be inhibition of
cyclooxygenase-3 (COX-3) in the CNS
Hepatotoxicity,
nephrotoxicity (rare)
Rash, hypothermia
Hypersensitivity to
acetaminophen
•
Gastrointestinal
hemorrhage,
ulceration,
perforation;
nephrotoxicity;
Stevens-Johnson
syndrome;
Gastrointestinal
disturbance, tinnitus
Gastrointestinal or
intracranial
bleeding
Coagulation defects
Asthma, urticaria, or
allergic-type
reactions after
taking NSAIDS,
due to risk of severe,
even fatal,
anaphylactic
reactions
Significant renal
insufficiency
Indications: Fever
Mild to moderate pain
Ibuprofen
Class: Propionic acids: (NSAID)
Mech: Inhibit cyclooxygenase-l (COXI) and cyclooxygenase-2 (COX-2),
decreasing the biosynthesis of
downstream eicosanoids and thereby
limiting the inflammatory response
Indications:
•
Mild to moderate pain
•
Fever
•
Osteoarthritis, rheumatoid
arthritis
•
Dysmenorrhea
•
Gout
N-Acetylcystine
Mech: Supplies cysteine to replenish
glutathione
Indications:
• Acetominophen Overdose
Although acetaminophen has
analgesic and antipyretic effects
similar to aspirin, the anti inflammatory effect of
acetaminophen is insignificant
because of its weak inhibition of
peripheral cyclooxygenases
•
Acetaminophen overdose is a
leading cause of hepatic failure
• Antidote for acetaminophen
overdose is N-acetylcysteine
ANTIDOTE FOR
ACETOMINAPHEN OD
Drug
Uses
Side effects
Contraindications
Therapeutic considerations
Celecoxib
Class: COX-2 inhibitor (NSAID)
Mech: Selectively inhibits COX-2
Indications:
•
Osteoarthritis, rheumatoid
•
arthritis in adults, and
•
ankylosing spondylitis
•
Primary dysmenorrhea
•
Acute pain in adults
•
Familial adenomatous
polyposis
Myocardial infarction, ischemic
stroke, heart failure;
gastrointestinal bleeding,
ulceration, perforation;
renal papillary necrosis;
exacerbation of asthma
Gastrointestinal disturbance,
peripheral edema
Hypersensitivity to
sulfonamides
Hypersensitivity to
celecoxib
Asthma, urticaria, or
allergic-type
reactions after taking
NSAIDs,
due to risk of severe, even
fatal,
anaphylactic reactions
Pain associated with
coronary
artery bypass graft surgery
•
Class: carboxylated imidazole
Mech appears to facilitate GABAminergic neurotransmission
by increasing the number of
available GABA receptors, possibly
by displacing endogenous inhibitors
of GABA binding
Indications:
IV anesthesia
intubation
Can cause adrenal insufficiency,
can cause seizure activity
Labor / Imminent Delivery
Very short acting.
Class: Opioid agonist
Mech: activates u-recptor in GI
tract, specifically in the myenteric
plexus, reduces muscle tone and
decreases peristalsis
•
•
•
•
•
Only COX-2
inhibitor still
on market!
Etomidate
Loperamide
OTCImodium
Indications:
• Diarrhea
•
•
Decreases efficacy of ACE
inhibitors
Incidence of gastropathy
and nephropathy may be
less than that associated
with NSAIDs, but may still
be significant
Valdecoxib and rofecoxib
recently withdrawn from
U.S. market due to
possible increase in
cardiovascular mortality
Septic shock
dry mouth
dizziness
drowsiness
vomiting
stomach pain, discomfort,
or distention (enlargement)
•
constipation
•
fatigue
anticholenergic effects (turns off
parasympathetics)
Under two years of age
Also has Anticholinergic effects.
Paralytic ileus
Opioid that only acts in the GI tract
(no effect on pain)
Drug
Uses
Side effects
Contraindications
Therapeutic considerations
Ranitidine
Class: H2 RECEPTOR
ANTAGONISTS (antihistamine
antacid)
Mech: Decreases acid
secretion by inhibiting
histamine binding to H2
receptors on parietal cells
Indications:
•
Peptic ulcer disease
•
Gastroesophageal reflux
disease (GERD)
•
Erosive esophagitis
•
Gastric acid
hypersecretion
Necrotizing enterocolitis in
fetus or newborn,
pancreatitis
Headache, dizziness, arthralgia,
myalgia,
constipation, diarrhea
Hypersensitivity
•
Ranitidine can be given IV
to treat hypersecretory
conditions or to treat
patients who are not able
to tolerate the oral
formulation
•
Has few side effects, or
drug interactions than
Cimetidine . It is also more
potent.
•
Unlike H1 blockers,
sedition is not common.
Class: Nicotinic receptor
agonist
Mech: Stimulate opening of
nicotinic ACh receptor
channel and produce
depolarization of the cell
membrane; succinylcholine
persists at the neuroeffector
junction and activates the
nicotinic receptor channels
continuously,
which results in inactivation
of voltage-gated sodium
channels so that they cannot
open to support further action
potentials (sometimes called
"depolarizing blockade‘)
Indications:
• Induction of
neuromuscular blockade in
surgery
Bradyarrhythmia, cardiac
arrest, cardiac arrhythmia,
malignant hyperthermia,
rhabdomyolysis, respiratory
depression Skeletal muscle
myopathies Muscle rigidity,
myalgia, raised intraocular
pressure
(Brand name =
Zantac)
Succinylcholine
• Intubation
Personal or family history
of malignant
hyperthermia
Skeletal muscle
myopathy
Upper motor neuron
injury
Extensive denervation of
skeletal muscle
Short duration of action
makes succinylcholine
in surgery drug of choice for
paralysis during intubation
Causes transient fasciculations