Quiz 3 Flashcards
autoimmune disease definition
broad spectrum of illnesses caused by development of autoimmunity, or self-reactivity. development of antibodies against self-antigens/host where body fails to recognize its own tissue. can be mild to severe. frequently results in inflammation w/in targeted tissues/organs
rheumatology
medical specialty that examines autoimmune diseases
autoimmune lab tests:
erythrocyte sedimentation rate (ESR), C-reactive protein, antinuclear antibody (ANA), rheumatoid factor
erythrocyte sedimentation rate (ESR)
AKA sed rate. non-specific test used as a marker for inflammation, infection, neoplasm, and tissue necrosis or infarction. can have frequent false elevation. often used in vague symptomatology. NOT DIAGNOSTIC
pathophysiology of ESR test
acute phase reactants (fibrinogen and immunoglobulins) in blood during inflammation and infection increase positive charge, making RBCs (typically negative) more neutral. leads to stacking of RBCs called Rouleaux
Westergren tube
sedimentation tube used in ESR
normal ESR
0-20 mm/h
factors that can interfere w/ ESR results
microcytosis or anemia (increase), polycythemia (decrease), abnormally shapred RBCs (sickled cells, spherocytes - decrease)
ESR is elevated in:
inflammatory states, autoimmune disease, infection, malignancy, age, renal disease, obesity. (>100 mm/h –> infection)
c-reactive protein (CRP)
acute phase reactant. function is to recognize and respond to inflammatory mediators and target damaged tissue for clearance. levels elevate quickly after injury, decline after injury is removed. test is NOT SPECIFIC
C-reactive protein elevated in:
infection, pregnancy, post-exercise, obesity, depression, MI, malignancy, autoimmune disease, RA, trauma
antinuclear antibody (ANA) test
measures presence of autoantibodies towards proteins that are specific to the nucleic acids (DNA/RNA) or complexes involved with the DNA/RNA.
antinuclear antibody (ANA) test is important in diagnosis of:
systemic lupus erythematosus (SLE); also an indicator of several other autoimmune diseases (Progressive systemic sclerosis/PSS-scleroderma, RA, sjogren, dermatomyositis, polyarteritis)
systemic lupus erythematosus (SLE)
chronic autoimmune inflammatory disease that affects multiple joints and organs. manifests with: fatigue, weight loss, arthralgias, myalgias, lymphadenopathy, facial rash, multiple organ involvement. butterfly rash w/ sparing of nasal folds is characteristic of lupus
pathophysiology behind ANA test
identified through use of indirect immunofluorescence. serial dilutions used; highest dilution at which ANA detected is reported as a result. pattern is reported also (peripheral, diffuse, speckled, nucleolar)
range for ANA test results
any value less than 1:40 dilution is negative, while a value greater than 1:160 is strongly positive
progressive systemic sclerosis (scleroderma)
autoimmune disease that manifests w/: fatigue, arthralgias, myalgias, skin thickening and hardening (characteristic), digital ulcers, multiple systemic manifestations
sjogren syndrome
autoimmune disease that manifests with: diminished lacrimal and salivary gland function (dry eyes and mouth), vaginal dryness, rhinitis and sinusitis, increased risk of lymphoma
polymyositis/dermatomyositis
autoimmune disease that manifests w/: proximal skeletal muscle weakness, pulmonary disease, dysphagia, polyarthritis, dermatologic manifestations (various skin rashes)
rheumatoid arthritis (RA)
autoimmune disease that manifests w/: joint stiffness, pain, swelling (symmetrical!) and eventual deformity of MCP and PIP joints; systemic manifestations (fatigue, cardiovascular and renal disease). can shorten lifespan
normal rheumatoid factor value
less than 30 IU/mL
rheumatoid factor test
primary test to dx RA. normal less than 30 IU/mL. composed primarily of IgM antibodies directed against the Fc fragment on IgG antibody. levels increase w/ higher levels of disease activity/severity. not specific for RA
rheumatoid factor is increased in:
RA, autoimmune diseases, chronic infections such as hepatitis, malignancy
RA vs. OA
symmetry, age, systemic symptoms vs. localized pain
normal thyroid stimulating hormone (TSH)
0.5-5.0 uIU/mL
control of the thyroid gland is regulated by:
the hypothalamus and pituitary gland
thyrotropin-releasing hormone (TRH) function
synthesized in the hypothalamus, transported to pituitary, where it stimulates the secretion of thyroid-stimulating hormone (TSH)
thyroid-stimulating hormone (TSH) function
binds to receptors on the thyroid gland and stimulates the release of thyroid hormones (triiodothyronine (T3) and thyroxine (T4))
T3 and T4 function
influence the metabolic rate of the body and many metabolic processes… increase: myocardial contractility and HR, mental alertness, ventilator drive, bone turnover, GI motility (hyperdefecation)
thyroid-stimulating hormone (TSH) test
measurement is sensitive and frequently used to assess function of thyroid gland; accurately measures deficiency or excess. when used w/ T3 or T4, can identify origin of thyroid dysfxn
hypothyroidism
caused by defect in hypothalamic-pituitary-thyroid axis. most common cause is primary hypothyroidism. can be caused by defect in thyroid gland (primary), decreased secretion of TSH from pituitary or decreased TRH from hypothalamus (secondary), medications, iodine deficiency, thyroidectomy, radiation to neck, radioiodine therapy after hyperthyroidism
primary hypothyroidism
defect in thyroid gland. most frequent cause of hypothyroidism
secondary hypothyroidism
decreased secretion of TSH from pituitary or decreased TRH from hypothalamus
autoimmune thyroiditis (Hashimoto’s thyroiditis)
most common cause of hypothyroidism. caused by autoimmune destruction and apoptosis of thyroid cells by TSH stimulation blocking antibody (TSBAb)
causes of secondary hypothyroidism
pituitary tumor, other infiltrating tumors, post-partum pituitary necrosis. less than 1% of hypothyroid pts.
symptoms of hypothyroidism
slowing down of metabolic processes (droopy dog): fatigue, dull mentation, dry skin, wt gain, bradycardia, constipation, cold intolerance
in hypothyroidism, TSH is:
increased (d/t thyroid gland dysfxn/failing. anterior pituitary sense decrease in T3/T4 and releases TSH)
T3 vs. T4
both produced by thyroid (90% T4, 10% T3). T3 more metabolically active. conversion of T4 to T3 occurs in various tissues (liver, kidneys, muscle).
Free T4
nearly all T4 bound to protein (thyroxine binding gloubulin, albumin, and prealbumin). free T4 = unbound, free METABOLICALLY ACTIVE form of T4
free T3
70% bound to proteins. amount free T3 in circulation is small
TSH, T3, T4 in hypothyroid states
serum TSH is elevated. then free T4 decreases. T3 remains constant even in disease
differentiating primary and central hypothyroidism: is TSH is decreased and free T4 is decreased, hypothyroidism may result from
disorder of hypothalamus or pituitary gland
subclinical hypothyroidism
“milder” hypothyroidism w/ similar sx. sx can be vague, nonspecific. pt may have high, normal, or mildly elevated TSH w/ normal free T4. frequently progresses to overt hypothyroidism
elevated TSH, decreased Free T4:
primary hypothyroidism
elevated TSH, normal free T4:
mild/subclinical hypothyroidism
normal/decreased TSH, decreased Free T4:
central hypothyroidism, nonthyroidial illness, drug effect
normal TSH and normal free T4:
normal/no hypothyroidism present
hyperthyroidism
AKA thyrotoxicosis. less common than hypothyroidism. most common form is Grave’s disease. inhibitory effect causes TSH decrease. can also be caused by: hyperplasia of thyroid cells, iodine rich medication (amiodarone) or contrast dye (rare). goiter
Grave’s Disease
most common form of hyperthyroidism. caused by autoantibodies that bind and activate TSH receptors of thyroid gland, causing inhibitory effect on the hypothalamic-pituitary axis and TSH level decreases.
symptoms of hyperthyroidism
(tazmanian devil)… anxiety, tremors, palpitations, perspiration, heat intolerance, wt loss (despite normal appetite), hyperdefecation
TSH in hyperthyroidism
suppressed
TSH and free T4/T3 in overt hyperthyroidism
low TSH, high free T4 and T3
subclinical hyperthyroidism
TSH is low but serum T3, free T3, and free T4 all normal. sx can be nonspecific. causes are the same. can put pt at increased CV risks, such as increased risk of a-fib
decreased TSH, increased free T4:
thyrotoxicosis (hyperthyroidism)
decreased TSH, normal free T4:
T3 toxicosis, mild or subclinical thyrotoxicosis, nonthyroidal illness
normal or increased TSH, increased Free T4:
TSH-secreting pituitary adenoma, thyroid hormone resistance syndrome, familial dysalbuminemic hyperthyroxemia
autoimmune thyroid disease
antibodies against thyroid follicular cells. antibodies present in Hashimoto’s and Grave’s. immune complexes lead to inflammation and cytotoxic effects on thyroid cells. a/w thyroglobulin antibodies, thyroid peroxidase antibodies, thyrotropin receptor antibodies
autoimmune thyroid disease: Hashimoto’s thyroiditis manifestations
hypothyroidism, thyroid failure, +/- goiter, follicular destruction
autoimmune thyroid disease: Grave’s disease manifestations
hyperthyroidism, goiter, orbitopathy, pretibial myxedema
parathyroid hormone (PTH)
secreted in parathyroid gland in response to hypocalcemia. decreases in normal serum calcium levels. test is used to dx hypocalcemia/hypercalcemia
parathyroid hormone (PTH) increased in:
hyperparathyroidism secondary to parathyroid cancer, hypocalcemia, chronic renal failure, malabsorption syndrome, vit. D deficiency
parathyroid hormone (PTH) decreased in:
surgical ablation of parathyroid gland, hypercalcemia, metastatic bone tumor, hypercalcemia of malignancy, vit. D intoxication
hormones produced by adrenal cortex
glucocorticoids, mineralocorticoids, sex steroids. all are synthesized from cholesterol
corticosteroids
glucocorticoids and mineralocorticoids
mineralocorticoids
ex. aldosterone. Na+, K+, and water homeostasis. regulate BP. produced in adrenal cortex
glucocorticoids
ex. cortisol. glucose homeostasis, immune suppression, metabolism of fats, amino acids and carbs, bone density. produced in adrenal cortex.
sex steroids
androgens. synthesized from cholesterol in the adrenal cortex and gonads
catecholamines
epinephrine, norepinephrine, and dopamine. produced in adrenal medulla.
hypothalamic-pituitary-adrenal axis in glucocorticoids
stress causes hypothalamus to release corticotrophic releasing hormone, which acts on pituitary to release adrenocorticotrophic hormone, which acts on adrenals to release cortisol
best method to test for cortisol
24 hr urine cortisol
dexamethasone suppression test
used to differentiate type of Cushing’s Syndrome (adrenal vs. pituitary). dexamethasone is a synthetic glucocorticoid that is more portent than cortisol.
ACTH (Adrenocorticotropic hormone) test
used in pts with abnormal dexamethasone suppression test to determine if Cushing’s syndrome is ACTH dependent. best to check when cortisol is low (midnight-2am). or, for adrenal insufficiency, check when cortisol level is highest (late morning). not useful as a stand alone test.
ACTH stimulation test
the most useful test for adrenal insufficiency. tests adrenal response to ACTH-like substance. cortisol level 1 hr after ACTH-like substance is given. lack of rise of cortisol level is indicative of adrenal insufficiency
CRH stimulation test
used to differentiate primary and secondary adrenal insufficiency. CRH is given and ACTH and cortisol levels are measures to evaluate pituitary response to stimulation from the hypothalamus. primary = elevated ACTH but no cortisol production. secondary = low ACTH and low cortisol.
aldosterone concentration test
used to diagnose hyper and hypoaldosteronism; can be measured serum or urine.
plasma renin activity
used to measure ability to convert angiotensinogen to angiotensin I; elevated in hyperaldosteronism
Cushing’s Syndrome
ACTH excess (resulting in high cortisol levels) caused by steroids, certain diseases or tumors
cushing’s syndrome signs and symptoms
rapid weight gain, moodiness, irritability, depression, memory changes, muscle weakness, osteoporosis, DM, HTN, immunosuppression, hair pattern changes, amenorrhea, infertility, moon facies, buffalo hump
Cushing’s disease
cushing’s syndrome secondary to a pituitary adenoma; excess production of ACTH by pituitary
tests used to dx Cushing’s
24 hr urine cortisol (main one), 24 hr salivary cortisol levels, dexamethasone suppression test, ACTH level/CRH stimulation test, CT adrenals, MRI pituitary
tx of Cushing’s
stop steroids (most common cause of Cushing’s syndrome), surgery/radiation (Cushing’s disease), cortisol suppressing drugs if pt unable or unwilling to undergo surgery
ACTH deficiency
secondary hypocortisolism. exogenous steroid use suppresses axis, sudden withdrawal causes symptoms.
ACTH deficiency/secondary hypocortisolism clinical manifestations
N/V, weakness, fatigue, fever, hypotension
ACTH deficiency/secondary hypocortisolism dx
insulin tolerance test. normal: low glucose, increase ACTH
ACTH deficiency/secondary hypocortisolism dx
exogenous glucocorticoids
primary Addison’s disease
destruction of adrenal cortex d/t autoimmune disorders, TB, or chronic infection. results in decreased cortisol and aldosterone
secondary Addison’s disease
lack of ACTH d/t drugs, tumors and infections of pituitary gland. results in decreased cortisol
symptoms of Addison’s disease
hypoglycemia, weight loss, hypotension, dizziness, vertigo, orthostasis, fatigue, disorientation, N/V/D, abd pain, tanning of skin(!)
causes of Addison’s disease
acute adrenal insufficiency: d/t steroid withdrawal or waterhouse Friderichsen syndrome. chronic: autoimmune, TB, AIDS, metastatic disease, hemochromatosis, sarcoid
dx of Addison’s
demonstrate abnormally low cortisol level (24 hr urine!, et al), determine if deficiency is ACTH sensitive (no = primary/adrenal, yes = secondary/hypothalamic or pituitary), seek treatable cause of primary disorder (CT/MRI tumors, auto antibodies for autoimmune disease)
tx of primary Addison’s disease
primary: replacement therapy: cortisol -> hydrocortisone; aldosterone -> fludrocortisone; secondary tx: find/tx tumors, stop offending drugs, tx infections
Conn’s syndrome
primary aldonsteronism; d/t increased level of aldosterone. causes HTN which leads to decreased blood K+, causing tiredness, muscle weakness, and polyuria. caused by adrenal adenoma.
tx of Conn’s syndrome
surgical removal (unilateral adrenalectomy), spirinolactone
secondary hyperaldosteronism
much more common than primary. increased aldosterone is d/t decreased renal perfusion which causes elevated PRA (plasma renin activity); commonly caused by CHF, nephrotic syndrome, cirrhosis
hypoaldosteronism
rare. primary: usually d/t destruction of adrenal glands. caused by misuse of steroids, TB, auto immune. elevated PAC, PRA. secondary: outside of adrenal gland, usually pituitary tumor
congenital adrenal hypoplasia (CAH)
refers to a group of disorders characterized by genital abnormalities due to deficiencies of the adrenal gland
causes of CAH
lack of an enzyme needed by the adrenal gland to make the hormones cortisol and aldosterone. w/o these hormones, the body produces more androgen which is a type of male sex hormone. this causes male characteristics to appear early or inappropriately
sx of CAH in males
enlarged penis, failure to regain birth weight, weight loss, dehydration, vomiting, precocious puberty, rapid growth during childhood but shorter than average final height; present early w/ salt wasting crisis resulting in dehydration, hypotension, hyponatremia, and hyperkalemia. or present later in childhood w/ early pubic hair, precocious puberty, and accelerated growth.
sx of CAH in females
ambiguous genitalia, failure to regain birth weight, weight loss, dehydration, vomiting, precocious puberty, rapid growth during childhood but shorter than average final height, infertility, irregular or absent menstruation, masculine characteristics
dx of CAH
serum electrolytes and glucose (low Na, high K, fasting hypoglycemia, elevated serum urea d/t associated dehydration), elevated plasma renin and ACTH levels, low cortisol, high 17-OHP, high androgens (esp. testosterone level), low aldosterone, urinary steroid profile, chromosomes, pelvic US
tx of CAH
peds endocrinologist -> oral drugs to boost hormone levels
effects of epinephrine and norepinephrine
short-term stress response (fight or flight): glycogen broken down to glucose (increased blood glucose), increased BP, increased breathing rate, increased metabolic rate, change in blood flow patterns leading to increased alertness and decreased digestive, excretory, and reproductive system activity
lab testing of adrenal function (medulla)
plasma metanephrines (preferred), urinary metanephrines (24 hr; preferred), plasma catecholamines, urinary catecholamines, urine VMA
pheochromocytoma
benign or malignant chromaffin tumor of adrenal medulla. may be fatal if untreated. 90% curable w/ surgery
pheochromocytoma signs and symptoms
5 P’s: pressure (HTN), pain (HA), perspiration, palpitation, pallor. (6th P: paroxyms). classic triad: pain, perspiration, palpitations
testing for pheochromocytoma
can dx clinically. 24 hr urine, imaging (CT abd, MRI)
overtraining syndrome (burnout)
persistent muscle soreness, persistent fatigue, elevated resting heart rate, increased susceptibility to infections, wt loss or gain, fluid retention, ammenorrhea, increased incidence of injuries, depression, mental breakdown
dx for overtraining syndrome
CBC, BMP, LFTs, UA, preg test, TSH, T4, cortisol, ACTH, ACTH stimulation, aldosterone, renin, sex hormones, inflammatory markers (sed rate, CRP), autoimmune
doping: drugs taken right before performance
stimulants, beta blockers
doping: drugs taken a long time before performance
anabolic steroids, EPO
doping: blocking or masking agents
diuretics, probenecid, epitestosterone
primary hemostasis
initially, arterial vasoconstriction occurs to reduce blood flow to the site of injury. the damaged cells of the epithelial lining release von Willebrand factor, which increases platelet adhesion to the epithelium. aggregation of platelets begins to occur -> formation of initial platelet plug. plug is “friable” and can wash away when vasorelaxation occurs
secondary hemostasis
involves intrinsic and extrinsic pathways
intrinsic pathway
contact activation: the blood is exposed to the surface of the damaged endothelium and collagen within that wall. this contact activates factor XII to XIIa
extrinsic pathway
traumatized tissue releases tissue factors which complex with factor VIIa
vitamin K dependent clotting factors
factors II, VII, IX, and X. also proteins C + S
factor I
fibrinogen
factor II
prothrombin
factor III
tissue factor or thromboplastin
factor VIII
anti-hemophilic factor
factor IX
Christmas factor
risk factors/signs for potential bleeding disorder
spontaneous bleeding episodes, hemorrhage post-op, bleeding post dental procedures, injections, or minor procedures. onset of bleeding after birth or in early childhood + positive family hx (genetics!) may point to a factor deficiency. medication/drug use, current systemic or chronic diseases (liver, kidney, thyroid)
suspect platelet defect if:
mucocutaneous bleeding of oral cavity, nasal, GI, GU; increased bleeding after cuts; small areas of superficial bleeding; variable amounts of bleeding after major surgery (immediate)
suspect clotting factor deficiency if:
deep tissue bleeding (joint and muscle), large hematomas, can be delayed bleeding post-op
common platelet disorders
von willebrand disease (most common), immune thrombocytopenia
common clotting deficiencies
factor VIII (hemophilia A), factor IX (hemophilia B), factor XI (hemophilia C)
increased risk of hypercoagulable disorders (AKA thrombophilia or bleeding diathesis) in:
pregnancy, cancer, estrogen therapy (can sometimes find hidden malignancy when looking for clot)
antithrombin III
an alpha-2 globulin made in the liver. it functions as a negative feedback moderator on the clotting cascade. is an anticoagulant. involved in mediating the balance of clotting and bleeding primarily by inactivation of thrombin and inactivation of Factor X to Xa
absence of antithrombin III would cause:
increased coagulation! coagulation would be constant, unchecked, and eventually result in depletion of clotting factors and ultimately, uncontrolled bleeding
antithrombin III test
used to monitor for hypercoagulable states
antithrombin is decreased in:
DVT, PE, phlebitis, heparin resistance, early age onset of thromboembolic events (inherited deficiency)
protein C
anticoagulant synthesized in the liver. inhibits factor Va and factor VIIIa. vitamin K dependent. can have genetic abnormalities of absence of these proteins that result in hypercoagulable state or intravascular coagulation. test with protein S.
protein S
anticoagulant synthesized in the liver. is a co-factor to protein C and enhances the function of protein C. vitamin K dependent. can have genetic abnormalities of absence of these proteins that result in hypercoagulable state or intravascular coagulation. test with protein C.
outomes of decreased protein C and S
venous thromboembolism (VTE) x7 increased risk; disseminated intravascular coagulation (DIC), neonatal purpura fulminans
factor V leiden
an inherited, mutated form of factor V. caused by single mutation from glutamine to arginine. normally, protein C breaks down factor V at one of 3 cleavage sites. in factor V leiden, protein C cannot break down factor F at one of the normal cleavage sites, leading to factor V leiden staying in circulation longer. results in increasing coagulation. normal result: negative. most common cause of thrombophilia in caucasians. majority of people are asymptomatic. 5% w/ DVT. homozygous= much greater risk of thromboembolism
test fr factor V leiden in:
pts w/ thrombotic event w/o predisposing factors, strong fam hx of thrombosis, FVT of pregnancy or w/ OCP use, arterial clot or thrombosis of unusual location
fibrinogen
a glycoprotein that circulates in plasma. is produced in liver. involved in homeostasis of blood clotting. is converted to fibrin via thrombin. is acute phase reactant. test is used in evaluation of bleeding disorders and to monitor for tx of DIC and fibrinolysis.
dysfibrinogenemia
dysfunctional fibrinogen. bleeding or thrombosis occurs. poor wound healing.
hypofibrinogenemia
reduced fibrinogen. usually mild bleeding.
hypodysfibrinogenemia
reduced AND dysfunctional fibrinogen. bleeding or thrombosis.
afibrinogenemia
rare genetic condition resulting in complete lack of fibrinogen (increase in consanguinity). less than 1 per mil people. mild to severe bleeding.
fibrinogen is increased in:
acute phase reactant! acute inflammation, trauma, acute infection, CVA, CAD, MI, preg, estrogen/OCP use
fibrinogen is decreased in:
congenital afibrinogenemia, hypofibrinogenemia, liver disease, DIC
bleeding time (test)
can be used to eval platelet function. subject to interobserver variability. assess platelets’ ability to form initial platelet plug in vessel wall. procedure: an incision 1mm deep x 10mm long is made into skin. stopwatch records time. every 30 sec a filter paper is applied over wound. once paper no longer absorbs blood, test time is recorded.
bleeding time test values:
normal: 1-9 minutes. platelet dysfunction 9-15 min. critical >15 min.
bleeding time is increased in:
decreased platelet count (less than 50,000), severe fibrinogen deficiency, von willebrand disease, meds (NSAIDS, abx, anticoags, TCAS), some connective tissue/autoimmune disease, liver failure, leukemia
prothrombin time/international normalized ratio (PT/INR)
AKA ProTime or INR. eval factors I, II, V, VII, X (extrinsic system and common pathway). if deficient, PT is prolonged. used to monitor warfarin therapy.
normal PT
11.0-12.5 seconds (85-100%)
normal INR
0.8-1.1
critical INR
> 5
preferred INR in DVT prophylaxis or tx
2.0-3.0
preferred INR in orthopedic surgery
2.0-3.0
preferred INR in a-fib
2.0-3.0
preferred INR in prosthetic valve prophylaxis
2.5-3.5
PT/INR increased in:
alcohol intake, diarrhea or malabsorption, vit. K deficiency, liver disease, genetic factor deficiency, warfarin, DIC
PT/INR decreased in:
inadequate dosage of warfarin in pt on anticoag therapy
Partial thromboplastin time (PTT)
measures the intrinsic pathway! commonly used to eval pt on heparin therapy. heparin inactivates factor II (prothrombin) and prevents factor III (TF/thromboplastin) and is commonly used to prevent and treat blood clots. PTT evaluates factors I, II, V, VIII, IX, X, XI, XII.
normal PTT
60-70 seconds. Patients receiving anticoagulant therapy: 1.5-2.5 times control value in seconds
normal aPTT
30-40 seconds. aPTT = activated PTT (activator added to test to shorten clotting time). Patients receiving anticoagulant therapy: 1.5-2.5 times control value in seconds
PTT increased in:
hemophilia and other clotting factor deficiencies, cirrhosis of liver, vit K deficiency, DIC, warfarin administration
PTT decreased in:
early DIC, extensive cancer
thrombin time
measures final step in coagulation cascade: fibrinogen -> fibrin. assesses amount of fibrin formation that is occurring (in seconds). decreased is rare. increased in congenital or impaired hypofibrinogenemia and DIC.
normal PT and prolonged aPTT:
disorder of intrinsic pathway, most likely hemophilia A or B (VIII and IX)
prolonged PT and normal aPTT
abnormality of extrinsic pathway; factor VII deficiency, warfarin therapy
tumor markers
elevation is not diagnostic of CA but can signal early presence, recurrence, or management of disease. no single marker today to specifically dx cancer on its own
prostate CA
early stages may be asymptomatic. some sx a/w prostate enlargement: urinary frequency, urgency, nocturia, urinary hesitancy, hematuria, hematospermia
prostate specific antigen (PSA)
a glycoprotein expressed in normal and neoplastic prostate tissue, usually higher concentration in prostate cancer cells. not specific, more frequently elevated in BPH and prostatitis. can have prostate CA and normal PSA. can have elevated PSA and no malignancy. can be normal in tumor/cell type variants or low testosterone.
normal prostate specific antigen (PSA)
0.00-4.00 ng/ml
PSA velocity
can be used to correlate w/ prostate cancer. >0.75 ng/ml/yr, serial, annual measurement used x3 years
free PSA
can be measured since ratio of free-to-total PSA is reduced in men w/ prostate CA (more bound PSA in prostate CA)
PSA test can be affected by:
medications, DRE (PSA must be drawn less than 1 hr after DRE or 24 hrs later), recent ejaculation, BPH, age (since prostate volume increases w/ age)
PSA increased in:
BPH, UTI, prostate CA, acute prostatitis, perineal trauma
decreased PSA d/t:
medications to tx BPH
sx of ovarian CA:
frequently vague and nonspecific, esp early in disease: abd bloating and distention, pressure near bladder and rectum, constipation, vaginal bleeding, GI sx (N/V), fatigue, wt loss, early satiety
CA125
cancer antigen 125. most often present in ovarian carcinoma. levels can vary w/ cell types. affected by level, course, and recurrence of ovarian CA. used in ovarian CA pts to assess tx and monitor for recurrence. NOT recommended as screening tool d/t immensely low specificity and sensitivity!
CA125 increased in:
ovarian CA, other types of carcinomas (breast, colon, liver, pancreatic, lung, hematologic,) infection, autoimmune, cardiac disease, women >60, female smokers. less likely to be elevated in obese women.
OVA-1
test that uses 5 biomarkers to: eval likelihood that adenexal mass is cancerous prior to surgery, identify if a pt w/ ovarian mass is high-risk, further manage surgical tx and f/u, identify cancers missed by CA125 alone
5 biomarkers tested in OVA-1
beta-2 microglobulin (increased in certain tumors, including ovarian CA), CA 125II (second generation CA125; increased in ovarian and gynecologic tumors), apolipoprotein A1 (involved in cholesterol transport but has some role in tumor suppression), prealbumin (decreases w/ tumor burden d/t metabolic changes that occur w/ CA), transferrin (down-regulated in ovarian CA)
sx of colon CA
hematochezia or melena, unexplained t loss, prolonged diarrhea or constipation, cramping abd pain, decrease in size or caliber of stools (pencil thin), abd distention, gas pain, fullness, vomiting, decreased energy
carcinoembryonic antigen (CEA)
protein normally found in fetal tissue. levels usually disappear after birth but may be present in colon. greatest use is in colon CA pts as factor in pt prognosis -> increased median survival w/ lower CEA at dx. not recommended as screening test (sensitivity can vary)
CEA can be increased in:
colon CA, GI tract CAs, breast CA, ovarian CA, pancreatic CA, thyroid CA, lung CA. can also be increased in benign conditions such as GI infection/inflammation, smoking
pancreatic CA: sx
abd pain, wt loss, jaundice, N/V/D, back pain, dark urine (from bilirubin)
cancer antigen 19-9
present in epithelial tissues of many organs, including the pancreas, stomach, gallbladder, and colon. most frequently used to monitor disease response to tx w/ pancreatic CA. not recommended as screening test (can be elevated in nl pts). pre-op levels correlate w/ outcome. rising levels correspond w/ recurrence and shorter survival time.
CA 19-9 increased in:
pancreatic CA, gastric CA, bile duct CA, colorectal CA, esophageal CA, colon CA, and benign conditions such as CF, pancreatitis, cirrhosis
sx of breast CA
painless mass, change in breast size or shape, skin changes of breast, nipple d/c (blody), nipple inversion (recent), swollen axillary lymph nodes. frequently asymptomatic in early stage
Cancer antigen 15-3
most often used in breast CA pts. most widely used serum marker in dx of breast CA. levels correspond w/ progression/regression of disease. higher levels correspond w/ greater tumor size or disease burden/stage and highest levels tend to occur w/ mets to bone/liver. also can be elevated in lung, pancreatic, or ovarian CAs. very low sensitivity and specificity, so use is limited
CA 27-29
variation of CA antigen 15-3 glycoprotein. uses a different epitope (portion of antigen) but also used as serum marker during breast CA
CA 15-3 increased in:
breast CA, liver CA, pancreatic CA, ovarian CA, endometrial CA, benign conditions such as benign breast disease, hepatitis, cirrhosis, TB, lupus
hepatocellular CA
primary tumor of liver manifests w/: upper abd pain, wt loss, early satiety, jaundice (uncommon). frequently asymptomatic until late stages. frequently a complication of underlying liver disease, such as hep B/C
alpha-fetoprotein (AFP)
produced in fetal liver, yolk sac, and GI tract, so high levels in infants. maternal AFP levels rise during pregnancy then decline. abnormal maternal AFP can indicated developmental defect. AFP most commonly used marker for hepatocellular CA in adults. levels do not correlate well w/ size of tumor, stage of CA or prognosis of disease. high false neg rate. serum levels nl in 40% HCC pts
AFP increased in:
hepatocellular CA, pancreatic CA, lung CA, stomach CA, colon CA, germ cell tumors of ovary, diseases of liver (hepatitis, alcoholic cirrhosis)
medullary thyroid CA
usually presents w/ a solitary thyroid nodule. CA of parafollicular cells of thyroid. represents 4% of thyroid cancers. pt may present w/ lymph node involvement, hoarseness, distant metastases
serum calcitonin
secreted in thyroid cells in response to elevated blood calcium levels. (parathyroid hormone is released in response to hypocalcemia). used in detection of medullary thyroid carcinoma (production of calcitonin is characteristic). important in bx. elevated levels correlates w/ tumor size pre-op. can also be elevated in other CAs in presence of bony metastases
calcitonin increased in:
medullary thyroid carcinoma, lung CA, breast CA, benign conditions such as thyroiditis, hyperparathyroidism
