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180 Cards in this Set
- Front
- Back
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Gold
(as a pharmacologic agent) |
Prevents further damage by suppressing macrophages and other phagocytes (depresses lysosomal enzyme activity)
Accumulates in synovial fluid to slow progression of bone and articular destruction One of the most effective agents for rapidly progressive rheumatoid arthritis (not used for acute attacks) Main use is in rheumatoid arthritis that is refractory to other treatments Contraindications: hepatic or kidney disease, pregnancy Adverse reactions: dermatitis, nephritis, proteinuria, agranulocytosis, chrysiasis (grey-blue discoloration of skin), aplastic anemia Rarely used due to severe side effects Overdose treated with dimercaprol Currently used agents: auranofin, gold sodium thiomalate |
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D-Penicillamine
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Unknown mechanism
Reduces rheumatoid factor (no longer used for RA - requires chronic use, high risk for serious side effects) Also used to chelate heavy metals (only acceptable use currently, due to side effects) Adverse effects: Dermatitis Nephritis Aplastic anemia |
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Methotrexate
(for inflammatory disorders) |
Folic acid antagonist - inhibits dihydrofolate reductase
Used in low doses to treat rheumatoid arthritis Adverse effects: Cytopenia Leukopenia Megaloblastic anemia Mucosal ulceration Nausea Liver cirrhosis Acute pneumonia-like syndrome |
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Anti-Tumor Necrosis Factor Agents
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Also called anti-rheumatic immune-modulators, biologic response modifiers
Very powerful - only for severe inflammatory conditions Reduce TNF effects or TNF levels Thalidomide Pentoxyfilline Infliximab Etanercept |
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Thalidomide
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Anti-tumor necrosis factor agent
Inhibits production and secretion of TNF Uses: leprosy, HIV associated skin lesions, multiple myeloma Extremely teratogenic - cannot be used in women of reproductive age unless negative pregnancy test and oral contraceptive use |
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Pentoxyfilline
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Anti-tumor necrosis factor agent
Phosphodiesterase inhibitor - inhibits TNF secretion Platelet aggregation inhibitor Use: acute alcoholic hepatitis |
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Infliximab
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Anti-tumor necrosis factor agent
Monoclonal antibody directed against TNF (human-mouse chimera) IV administration Uses: rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, moderate to severe ulcerative colitis and Crohn's Adverse effects: Can increase risk for acute onset life-threatening sepsis Increase risk of acquisition and spread of TB Increase risk of lymphoma and other cancers Associated with higher incidence of MS, myelitis, opic neuritis Risk for serum sickness Headache Dyspnea Abdominal pain |
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Etanercept
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Anti-tumor necrosis factor agent
Recombinant TNF receptor - binds TNF in the bloodstream Administered subcutaneously Uses: rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, juvenile rheumatoid arthritis Adverse effects: Potential for acute onset life-threatening sepsis Increased risk of TB acquisition and spread Associated with higher incidence of developing MS, myelitis, optic neuritis |
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Adalimumab
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Anti-tumor necrosis factor agent
Fully human monoclonal antibody directed against TNF Uses: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease Not approved for use in children Adverse effects: Aplastic anemia Thrombocytopenia Leukopenia Increased incidence of MS, optic neuritis, myelitis May worsen heart failure (monitor closely) |
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Gout
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Metabolic disorder marked by increased amounts of uric acid (either from increased production or decreased excretion)
Urate precipitates in joints and kidneys Acute attacks often due to high alcohol consumption, high purine diet, kidney disease Chronic may be due to kidney disease or malignancy |
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Colchicine
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DOC for acute gout attacks (although first attack often treated with NSAID)
Binds tubulin, disrupting cell's ability to migrate to affected area and inhibiting synthesis and release of leukotrienes Prevents macrophages from moving to affected site - prevents further irritation Does not prevent progression, but has suppressive effect in decreasing number of future attacks Contraindicated in pregnancy Use with caution in hepatic and cardiovascular disease |
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Allopurinol
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Used in treatment of gout
Inhibits xanthine oxidase - inhibits uric acid production Adverse effects: Hypersensitivity reactions (skin rashes - months to years of chronic use) |
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Probenecid
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Used in treatment of gout
Uricosuric agent - blocks tubular reabsorption of uric acid, causes greater excretion Requires high doses - low doses compete with urate at renal transporters and make gout worse Will raise plasma concentration of drugs that compete at renal transporters |
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What two specific groups of patients may have chronic gout?
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Lesch-Nyhan syndrome
Patients being treated for malignancies (overabundance of nucleic acid from dying malignant cells) |
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Lesch-Nyhan Syndrome
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X-linked recessive
Symptoms: Hyperuricemia Mental retardation Compulsive biting of lips and fingers (self mutilation) Due to deficiency in hypoxanthine-guanine phosphoribosyl tranferase (HGPRT) |
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What NSAID should never be used to treat gout?
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Aspirin
Competes with uric acid at renal transporters (less uric acid excreted) |
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ATP Yields:
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FADH2: 2
NADH: 3 Acetyl CoA: 12 Pyruvate: 15 Glycolysis (anaerobic): 2 Glycolysis (aerobic): 8 Glucose (complete oxidation): 38 Fatty acid: 129 Gluconeogenesis (from pyruvate): -12 Urea synthesis: -4 Glycerophosphate shuttle: 2 per NADH Malate shuttle: 3 per NADH |
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Metabolism:
Glycolysis |
Carbohydrates
Key enzyme: phosphofructokinase-1 Allosteric inhibitors: ATP, citrate Allosteric activators: AMP, fructose 2,6-dp If enzyme is phosphofructokinase-2, phosophorylation inhibits |
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Metabolism:
Gluconeogenesis |
Carbohydrates
Key Enzyme: fructosediphosphatase-1 Allosteric inhibitors: AMP, fructose 2,6-dp Allosteric activators: ATP, citrate If enzyme is fructosediphosphatase-2, phosphorylation activates |
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Metabolism:
Glycogenolysis |
Carbohydrates
Key enzyme: glycogenphosphorylase Effect of phosphorylation: activates |
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Metabolism:
Glycogen Synthesis |
Carbohydrates
Key enzyme: glycogen synthetase Effect of phosphorylation: inhibits |
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Metabolism:
Pentose Phosphate Shunt |
Carbohydrates
Key enzyme: glucose-6-phosphate dehydrogenase Allosteric inhibitors: NADPH |
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Metabolism:
Lipolysis |
Fats
Key enzyme: carnitine acyltransferase Allosteric inhibitors: malonyl CoA |
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Metabolism:
Fat Mobilization |
Fats
Key enzyme: hormone sensitive lipase Effect of phosphorylation: activates |
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Metabolism:
Lipid Synthesis |
Fats
Key enzyme: acetyl-CoA carboxylase Allosteric activators: citrate Effect of phosphorylation: inhibits |
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Metabolism:
Cholesterol Synthesis |
Fats
Key enzyme: HMG CoA reductase Allosteric activators: cholesterol Effect of phosphorylation: inhibits |
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Metabolism:
Ketone Body Synthesis |
Key enzyme: HMG CoA synthase
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Metabolism:
Purine Synthesis |
Key enzyme: amidotransferase
Allosteric inhibitors: AMP, GMP, IMP |
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Metabolism:
Citric Acid Cycle |
Key enzyme: pyruvate dehydrogenase 1
Allosteric inhibitors: acteyl CoA, NADH Effect of phosphorylation: inhibits Key enzyme: citrate synthase Allosteric inhibitors: acetyl CoA, ATP, NADH |
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What are steroid hormones made from?
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Cholesterol
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Steroid Class:
Sterols |
Example: cholesterol
Number of C atoms: 27 |
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Steroid Class:
Bile Acids |
Examples: glycocholate, taurocholate
Number of C atoms: 24 |
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Steroid Class:
Glucocorticoids |
Example: cortisol
Number of C atoms: 21 |
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Steroid Class:
Mineralocorticoids |
Example: aldosterone
Number of C atoms: 21 |
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Steroid Class:
Gestagens |
Example: progesterone
Number of C atoms: 21 |
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Steroid Class:
Androgens |
Examples: testosterone, androstenedion, DHEA
Number of C atoms: 19 |
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Steroid Class:
Estrogens |
Examples: estradiol, estrogen
Number of C atoms: 18 |
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What are the three areas of the adrenal cortex and the steroids produced in each?
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Zona glomerulosa - mineralocorticoids
Zona fasciculata - glucocorticoids Zona reticularis - Androgens |
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What is caused by 17-alpha-hydroxylase deficiency?
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Male: ambiguous genitalia
Female: primary amenorrhea |
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What is caused by 21-alpha-hydroxylase deficiency?
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Most common defect of corticoid synthesis (95%)
Male: precocious puberty Female: ambiguous genitalia (both due to increased DHEA) Salt wasting in 50-60% of patients (lack of aldosterone) |
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What is caused by 11-beta-hydroxylase?
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Male: precocious puberty
Female: ambiguous genitalia (both due to increased androgens) Salt retention - leads to hypertension, hypokalemia |
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What is insulin's effect on:
Fat? Sugar? Protein? |
General anabolic action
Fat (anabolic): synthesis Sugar (anabolic): Uptake in muscle, fat Glycolysis in liver, muscle Glycogen synthesis in liver, muscle Protein (anabolic): synthesis |
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What is glucagon's effect on:
Fat? Sugar? Protein? |
Fat (catabolic): lysis
Sugar (catabolic): Gluconeogenesis in liver Glycogenolysis in liver Protein (catabolic): increases uptake of amino acids in liver for gluconeogenesis |
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What is GH's effect on:
Fat? Sugar? Protein? |
Promotes synthesis of protein at expense of fat and sugars
Fat (catabolic): lysis Sugar (catabolic): gluconeogenesis in liver Protein (anabolic): synthesis |
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What is cortisol's effect on:
Fat? Sugar? Protein? |
Increases blood sugar levels and build-up of glycogen stores at expense of fat and protein
Fat (catabolic): lysis and redistribution Sugar (anabolic): Inhibits uptake in muscle, fat Gluconeogenesis in liver Glycogen synthesis in liver Protein (catabolic): degradation |
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What is epinephrine's effect on:
Fat? Sugar? Protein? |
Fat (catabolic): lysis
Sugar (catabolic): Increases uptake in muscle Glycolysis in muscle Gluconeogenesis in liver Glycogenolysis in liver, muscle Protein: none |
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What is the difference between nucleosides and nucleotides?
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Nucleosides: purines or pyramidines linked to a pentose sugar
Nucleotides: phosphates (mono, di, or tri) of the nucleoside |
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What are the purines?
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Adenine
Guanine |
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What are the pyramidines?
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Uracil
Cytosine Thymine |
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Adenine
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Purine
Nucleoside: adenosine Nucleotide: adenylate (AMP) |
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Guanine
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Purine
Nucleoside: guanosine Nucleotide: guanylate (GMP) |
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Uracil
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Pyrimidine
Nucleoside: uridine Nucleotide: uridylate (UMP) |
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Cytosine
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Pyrimidine
Nucleoside: cytidine Nucleotide: cytidylate (CMP) |
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Thymine
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Pyrimidine
Nucleoside: deoxythymidine Nucleotide: deoxythymidylate (dTMP) |
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What are the processes by which purines are made?
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De novo synthesis (in liver):
Phosphoribosyl pyrophosphate -> IMP -> AMP or GMP -> ADP or GDP Salvage of purine bases: Hypoxanthine -> IMP Guanine -> GMP Adenine -> AMP |
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What is the process of degradation of purine bases?
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In liver
Adenosine -> Inosine -> Hypoxanthine -> Xanthine OR Guanosine -> Guanine -> Xanthine Xanthine -> Uric Acid |
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What are the processes by which pyrimidines are made?
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De novo (in liver):
Glutamine -> Carbamoylphosphate -> OMP -> UMP UTP -> CTP dUMP -> dTMP Salvage of pyrimidine bases: Uracil -> UMP Cytosine -> CMP |
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What is the process of degradation of pyrimidine bases?
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In liver
Pyrimidine rings can be opened and completely degraded Cytosine -> CO2, NH4+, beta-alanine Thymine -> CO2, NH4+, beta-amino-isobutyrate |
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Operon
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In prokaryotic DNA
Operational unit that is either "on" or "off" Consists of promoter, operator, and one or more structural genes |
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Promoter
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In prokaryotic DNA
RNA polymerase binds to promoter Located on 5'-end of operon ("upstream") |
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Operator
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In prokaryotic DNA
Located between promoter and structural genes Binding site of repressors If repressor binds to operator, operon is "off" (polymerase can't proceed) |
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Repressor
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Prokaryotic protein
Regulatory protein that binds to operator and prevents transcription |
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Regulator Gene
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In prokaryotic DNA
Codes for repressor |
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Eukaryotic Transcription
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No operon - each structural gene has its own promoter containing many different response elements (binding sites for regulatory proteins)
Regulatory proteins can bind to several promoters activating a set of structural genes (which may be located on different chromosomes) Transcription is regulated by various combinations of regulatory proteins |
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Transcription Factor
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Eukaryotic
Binds to TATA box (part of promoter) RNA polymerase does not recognize promoter without transcription factor |
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Inducers
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Eukaryotic
Bind to nuclear receptor protein Inducer-receptor complex binds to DNA and activates some genes, inactivates others Example: steroid hormones |
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Enhancers
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Eukaryotic
Regulatory DNA sequence Can be upstream or downstream of promoter May be located several thousand base pairs from starting point of transcription Loops in DNA bring enhancers near promoter region |
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Around what age does fusion of the bones of the innominate occur?
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Age 20
Ilium - Ischium - Pubic bone All fuse at acetabular notch |
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What are the main ligaments of the pelvis?
Which are accessory ligaments and true ligaments? |
Sacrotuberous ligaments
Sacrospinous ligaments Iliolumbar ligaments (Accessory) Sacroiliac ligaments (True) |
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Sacrotuberous Ligaments
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Accessory ligaments of pelvis
Connect sacrum to ischial tuberosity |
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Sacrospinous Ligaments
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Accessory ligaments of pelvis
Connect sacrum to ischial spines Divides greater and lesser sciatic foramen |
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Iliolumbar Ligaments
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Accessory ligaments of pelvis
Attach L4/L5/iliac crests to SI joints (for stability) Usually first to become tender with lumbosacral dysfunction 3 ligaments: anterior, posterior, interosseous |
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Ganglion Impar
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Site of fusion of left and right sacral sympathetic trunks
Lies just anterior to coccyx |
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Pelvic Diaphragm
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Comprised of (muscles):
Levator ani (puborectalis, pubococcygeus, iliococcygeus) Coccygeus Function: Supports pelvic viscera and pelvic floor Aids in raising pelvic floor Constricts lower rectum and vagina |
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Piriformis
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Origin: inferior anterior sacrum
Insertion: greater trochanter of femur Innervation: S1, S2 Functions: External rotation of thigh Extension of thigh Abduction of thigh when hip is flexed |
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Iliopsoas
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Origin:
Psoas - T12-L5 vertebrae Iliacus - iliac crest, iliac fossa, sacral ala, anterior sacroiliac ligaments Join within true pelvis Insertion: Psoas - lesser trochanter of femur Iliacus - psoas major tendon, body of femur inferior to lesser trochanter Innervation: Psoas - L1-L3 (lumbar plexus) Iliacus - femoral nerve (L2, L3) Function: flexion of thigh and stabilization of hip joint |
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What is the difference between the true and false pelvis?
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True: funnel shaped area bounded anteriorly by the pubic bones and posteriorly by the sacrum
False: technically part of abdomen - located in area between ilia |
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What are the signs of a flexion contracture of the iliopsoas?
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L1 and/or L2 flexed, sidebent, rotated toward side of contracture
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Nerves and Innervations:
Lumbar Plexus |
T12 - L4
Muscles innervated: Iliopsoas Quadriceps Adductor group Sartorius Gracilis (abdomen and thigh) Sensation: Thigh Buttocks Lower abdomen Pubic area |
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Nerves and Innervations:
Sacral Plexus |
L4-5, S1-3, portion of S4
Innervation (motor and sensory): Pelvis Lower extremity Parasympathetic innervation (S2-4) to left colon and pelvic organs Nerve branches: Sciatic Pudendal Superior and inferior gluteal |
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Sciatic Nerve
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Branch of sacral plexus
Originates from L4-S3 Usually runs through greater sciatic notch just below piriformis Anomalies exist, including nerves that run through piriformis |
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Inherent Motion of Sacrum
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Associated with cranial cycle of flexion/extension
Craniosacral extension: dips forward into sacral flexion (nutation) Craniosacral flexion: tips backward into sacral extension (counternutation) Axis of motion: S2 horizontal axis |
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Respiratory Motion of Sacrum
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Inhalation: sacral base moves posteriorly (extension, counternutation)
Exhalation: sacral base moves anteriorly (flexion, nutation) Axis: horizontal S2 |
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Postural Motion of Sacrum
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Flexion of torso: sacral base moves posteriorly (extension, counternutation)
Extension of torso: sacral base moves anteriorly (flexion, nutation) Axis: S3 transverse |
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Dynamic Motion of Sacrum
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Occurs with ambulation
Step forward with left/weight on right: right sacral oblique axis engaged Step forward with right/weight on left: left sacral oblique axis engages |
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What are the two rules for L5 dysfunction affecting the sacrum?
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1. L5 rotation is opposite of sacral rotation
2. L5 sidebending engages ipsilateral sacral oblique axis |
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Anterior Innominate Rotation
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One innominate rotates anteriorly with respect to the other
Findings: ASIS inferior PSIS superior Longer leg on ipsilateral side Positive standing flexion and ASIS compression tests on affected side Etiology: Tight quadriceps Rectus femoris or adductor group dysfunction Symptoms: Hamstring tightness Sciatica (due to piriformis dysfunction) |
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Posterior Innominate Rotation
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One innominate rotates posteriorly with respect to the other
Findings: ASIS superior PSIS inferior Shorter leg ipsilaterally Positive standing flexion and ASIS compression test on affected side Etiology: tight hamstrings Symptoms: Groin pain Medial knee pain (due to sartorius dysfunction) |
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Superior Innominate Shear
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One innominate more superior than the other
Findings: ASIS superior PSIS superior Pubic ramus superior Positive standing flexion and ASIS compression tests on affected side Etiology: Fall on or thrust up the ipsilateral gluteal area Surprise step off curb into a hole Symptoms: Pelvic pain Contralateral SI joint pain Low back pain |
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Inferior Innominate Shear
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One innominate more inferior than the other
Findings: ASIS inferior PSIS inferior Pubic ramus inferior Positive standing flexion and ASIS compression tests on affected side Etiology: Trauma Car accident Symptoms: Pelvic pain Contralateral SI joint pain |
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Superior Pubic Shear
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One pubic bone superior to the other
Findings: Pubic bone superior ASIS level or superior PSIS level or inferior Positive standing flexion and ASIS compression tests on affected side Etiology: Tight rectus abdominis muscle Unusual trauma Posterior innominate rotation Third trimester pregnancy or delivery Symptoms: Tender inguinal area with or without dysuria or frequency |
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Inferior Pubic Shear
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One pubic bone is inferior to the other
Findings: Pubic bone inferior ASIS level or inferior PSIS level or superior Positive standing flexion and ASIS compression tests on affected side Etiology: Tight adductor muscles Unusual trauma Anterior innominate rotation Third trimester pregnancy or delivery Symptoms: pelvic or SI joint pain |
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Innominate Inflare
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Innominate is rotated medially
Findings: ASIS more medial Taut posterior pelvic muscles Positive standing flexion and ASIS compression tests on affected side Etiology: trauma Symptoms: sometimes dysuria and/or frequency |
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Innominate Outflare
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Innominate is rotated laterally
Findings: ASIS more lateral Lax posterior pelvic muscles Positive standing flexion and ASIS compression tests on affected side Etiology: trauma Symptoms: pelvic or SI joint pain |
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Bilateral Sacral Flexion
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Sacral base more anterior (whole base)
Findings: Deep superior sulci Shallow ILAs Increased lumbar lordosis Negative spring test Negative (false negative) seated flexion test Etiology: Delivery (VERY common in postpartum women) Trauma Symptoms: low back pain that worsens with backward bending |
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Bilateral Sacral Extension
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Sacral base positioned more posteriorly (whole base)
Findings: Shallow superior sulci Deep ILAs Decreased lumbar curvature Positive spring test Negative (false negative) seated flexion test Etiology: trauma Symptoms: low back pain that worsens with forward bending |
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Unilateral Sacral Flexion
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Sacral base anterior unilaterally
Most common type of sacral shear Findings: Deep superior sulcus on affected side Shallow ILA on affected side Negative spring test Positive seated flexion test on affected side Shorter leg on affected side Etiology: Surprise step into hole or off curb Lumbar dysfunction Symptoms: low back pain |
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Unilateral Sacral Extension
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Sacral base is posterior unilaterally
Findings: Shallow superior sulcus on affected side Deep ILA on affected side Positive spring test Positive seated flexion test on affected side Longer leg on affected side Etiology: Trauma Lumbar Dysfunction Symptoms: low back pain |
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Forward Sacral Torsion
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Rotation in same direction as axis
R-on-R, L-on-L Findings: Deep superior sulcus contralateral to rotation Shallow ILA ipsilateral to rotation Lumbar sidebending ipsilateral to oblique axis Lumbar rotation opposite of sacral rotation Negative spring test Positive seated flexion test contralateral to oblique axis Etiology: trauma, lumbar dysfunction Symptoms: low back pain with SI, inguinal, or groin pain (exacerbated by backward bending) |
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Backward Sacral Torsion
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Rotation opposite of axis
R-on-L, L-on-R Findings: Shallow superior sulcus ipsilateral to rotation Deep ILA contralateral to rotation Lumbar sidebending to ipsilateral side of oblique axis L5 rotated opposite rotation Positive spring test Positive seated flexion test on side contralateral to oblique axis Etiology: trauma, lumbar dysfunction Symptoms: low back pain or SI discomfort (exacerbated by bending forward or walking) |
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What should be treated before treating any sacral dysfunction?
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Any L5 dysfunction
Usually spontaneously resolves sacral dysfunction |
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Endometrial Polyps
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Focal thickening of endometrium
Benign Often asymptomatic Estrogen sensitive Possible genetic relationship |
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Endometrial Hyperplasia
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Thickening of all endometrial wall - "stripe thickening"
Pre-malignant Stimulated by high estrogen (mainly) or low progesterone stimulation (progesterone inhibits estrogen) Risk factors: PCOS Age over 40 Estrogen treatment Early menarche Late menopause Granulosa-theca cell tumor Nulliparity Obesity Type II diabetes Hypertension |
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Endometrial Carcinoma
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Most common invasive cancer of female genital tract
Develops from hyperplasia |
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What are the disorders of the cervix?
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Non-neoplastic: cervicitis, cervical polyps
Pre-cancerous: CIN (cervical intraepithelial neoplasia) Carcinoma (invasive) |
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Cervicitis
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Non-neoplastic
Inflammation of the cervix Causes: Gardnerella vaginalis Trichomonas vaginalis Candida albicans Chlamydia trachomatis |
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Cervical Polyps
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Non-neoplastic (not neoplasms)
Represent proliferation of cervical epithelium in response to inflammation |
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CIN
(Cervical Intraepithelial Neoplasia) |
Pre-cancerous
Usually involves squamocolumnar junction Three grades Major association with HPV types 16, 18, 30s, 40s, 50s (although HPV is not the only factor) Disorganized epithelial growth due to HPV's inhibition of tumor suppressors p53 and RB May spontaneously regress or may develop into invasive carcinoma TX: Cryotherapy Laser Loop electric excision procedure (LEEP) Cone biopsy (types II and III) |
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What are the grades of CIN?
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CIN I:
Low-grade intraepithelial lesion Mild dysplasia of upper layer of cervical epithelium CIN II: High-grade intraepithelial lesion More severe dysplasia Affects various cells throughout entire epithelial thickness CIN III: High-grade intraepithelial lesion Carcinoma in situ Entire cervical epithelial layer is replaced by neoplastic cells Demonstrates no invasion beyond underlying basement membrane |
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Invasive Cervical Carcinoma
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Neoplastic development of cervical epithelium with invasion through underlying basement membrane
Stage 0: carcinoma in situ (CIN III) Stage 1: invasive carcinoma confined to cervix Stage 2: invasive carcinoma extends beyond cervix but not onto pelvic wall, and if vagina is involved does not spread to lower 1/3 Stage 3: invasive carcinoma has extended to pelvic wall Stage 4: invasive carcinoma has extended beyond pelvic wall or has involved rectal or bladder mucosa (with or without metastases) |
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Polycystic Ovarian Syndrome
(PCOS) |
Also called Stein-Levanthal Syndrome
Chronic anovulation with symptoms of androgen excess along with obesity Thought to be due to excess LH production by anterior pituitary Symptoms: infertility, amenorrhea or oligomenorrhea, acne, hirsutism (usually also obesity, potential for type II diabetes) >2:1 LH:FSH ratio High androstenedione, testosterone, estrone Process: Constant high LH stimulates ovarian theca cells to produce androgen (causes acne and hirsutism) - magnified in obese women due to adipose cell conversion of androgen to estrone Estrone has negative feedback effect on anterior pituitary, reducing FSH production Decreased FSH results in decreased follicular development in ovary - prevents formation of ovum ready for ovulation, therefore no ovulation = infertility Many anomalies in ovarian and pituitary hormone production results in amenorrhea or oligomenorrhea |
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Endometriosis
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Presence and proliferation of non-neoplastic endometrial tissue outside the uterine cavity
Develop multiple nests of endometrial cells throughout structures in peritoneal cavity (#1 site is ovary, also uterine ligaments, rectovaginal area, pelvic peritoneum) Bleeding can occur into ectopic endometrial tissue -- if on the ovary, can develop chocolate cysts (collection of old blood) Symptoms: Dysmenorrhea Dyschezia Dyspareunia |
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Uterine Leiomyoma
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Fibroid - smooth muscle tumor
Most common uterine tumor and overall most common tumor in women Benign Estrogen sensitive - grows during reproductive years, regresses during menopause Characteristic whorled pattern of smooth muscle bundles More common in blacks Symptoms: Abnormal menstrual bleeding (most common) Urinary frequency Impaired fertility Increased risk of spontaneous abortion or fetal malpresentation Increased risk of postpartum hemorrhage |
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Hydatidiform Mole
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Due to abnormal ovum fertilization that ultimately causes excessive trophoblastic development in the form of grape-like cysts
Complete: 2 X chromosome sperm that have fertilized 1 enucleate ovum Incomplete: fertilization of 1 ovum with 2 or more sperm (yielding triploidy or more) Cystic swelling of villi (grape like cysts) Trophoblastic (placental) proliferation Very high beta-hCG Uterus larger than expected for gestational age |
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Choriocarcinoma
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Frequent and early metastases - diagnosis usually too late for intervention
Malignant neoplasm of trophoblastic cells (placenta) Initially asymptomatic Very high beta-hCG Late findings: irregular spotting of brown blood foul smelling fluid Risk factors: Retained GTN Retained placenta after delivery or abortion May develop spontaneously in ovary as type of grem cell tumor |
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Fibrocystic Change of Breast
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Multiple bilateral nodules
"Lumpy bumpy" breast Fluctuate in size and tenderness with menstrual cycle Benign |
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Breast Cancer
(Characteristics) |
Typically one solitary nodule
Usually unilateral Often non-tender in early stages Does not fluctuate with menstrual cycle |
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Fibroadenoma of Breast
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Benign
Fibrous and glandular tissue - stromal tumor Single sharply circumscribed mass - mobile, marble shaped and sized Usually <30 years of age Mildly increased risk of subsequently developing breast cancer |
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Phylloides Tumor of Breast
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Benign (if becomes malignant, called cystosarcoma phylloides tumor)
Stromal tumor Usually occurs >60 years of age Grows quickly Rapidly becomes huge log-shaped tumor |
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Intraductal Papilloma
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Benign
Epithelial tumor Tumor comprised of ductal epithelial cells Nipple discharge frequently bloody or serous |
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Ductal Carcinoma In Situ
(DCIS) |
Malignant
Non-invasive carcinoma (cells do not cross basement membrane) Neoplasm of ductal epithelial cells 5 types: Comedocarcinoma - solid sheets of malignant cells with central areas of necrosis that become calcified (microcalcifications) Solid Cribriform Papillary Micropapillary |
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Invasive Ductal Carcinoma
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Malignant
Neoplasm of ductal epithelium Most common breast cancer Often scirrhous (hard) May see peau d'orange, nipple retraction, dimpling May palpate fixed mass |
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Lobular Carcinoma In Situ
(LCIS) |
Malignant
Rare Tumor of lobules, terminal ducts, ductules (acini) Never forms calcifications or masses Tend to be bilateral Signet ring cells common |
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Invasive Lobular Carcinoma
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Malignant
Uncommon Diffusely invasive through breast (makes detection difficult) Tend to be bilateral (high risk of recurrence in opposite breast - recommend bilateral removal) High metastasis rate (CSF, ovary, bone marrow, uterus) Confers rubbery consistency to breast Signet ring cells common Single file arrangment of neoplastic cells |
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Paget's Disease of the Nipple
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Malignant
Form of DCIS that extends from nipple ducts into contiguous nipple skin and areola (involvement of epidermis by malignant cells called Paget cells) Palpable mass usually present in breast - represents invasive ductal carcinoma that started as DCIS Nipple may be fissured, ulcerated, oozing, hyperemic, edematous |
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Medullary Carcinoma of Breast
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Malignant
Uncommon Young women Often associated with BRCA1 gene mutation Soft fleshy consistency |
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Colloid (Mucinous) Carcinoma of Breast
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Malignant
Uncommon Older women Gelatinous consistency Usually receptor positive |
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Tubular Carcinoma of Breast
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Malignant
10% of mammographically identified tumors Conspicuously spiculated Late 40s age range Multifocal and unilateral OR bilateral Usually receptor positive Excellent prognosis |
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Sarcoma of Breast
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Malignant
Stromal tumor Usually very bulky and palpable Angiosarcoma Rhabdomyosarcoma Leiomyosarcoma Chondrosarcoma Osteosarcoma |
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Mammographic Findings of Breast Tumors
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Invasive ductal or tubular: spiculated density with irregular infiltration of surrounding tissue
Cyst or fibroadenoma: well circumscribed density with smooth borders Medullary or mucinous carcinoma: well circumscribed with smooth border Lobular carcinoma: distortion of breast without discrete density Malignant lesion (ex, DCIS): small irregular numerous and clustered or linear and branching calcifications |
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What are the most common metastatic sites for breast cancer?
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Lungs
Bone Liver Adrenals Brain Meninges |
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What is the role of estrogen and progesterone receptors in breast cancer?
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Found in 50-85% of breast tumors
More common in post menopausal patients Yield slightly better prognosis If present, allow almost 3/4 of receptor positive tumors to regress with hormonal manipulations |
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What are the oncogenes and tumor suppressor genes associated with breast cancer?
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Oncogenes: c-erb-B2 (HER-2, neu)
Tumor suppressor: BRCA-1, BRCA-2, p53 |
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Glossitis
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Inflammation of tongue
Associated with vitamin B2 (riboflavin) or B12 (cobalamin) deficiency |
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Cheilosis
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Drying and scaling of lips with fissuring at corners of mouth
Associated with vitamin B2 (riboflavin) deficiency |
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Smooth Beefy-Red Tongue
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Atrophy of papillae and mucosa to expose underlying vasculature
Associated with advanced vitamin B12 (cobalamin) deficiency |
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Strawberry Tongue
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White coated tongue through which hyperemic papillae poke, giving appearance like bumps on a strawberry
Associated with scarlet fever |
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Koplik's Spots
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Ulcerations on buccal mucosa
First sign of measles |
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What is the terminology used for esophageal diverticula?
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Termed for location:
Zenker's - above upper esophageal sphincter Traction - midpoint of esophagus Epiphrenic - above lower esophageal sphincter Termed for number of layers involved: Pulsion - herniation of mucosa only (false diverticulum) True - all layers |
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Acute Erosive Gastritis
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Focal inflammation/damage of gastric mucosa
Risk factors: Alcohol NSAIDs Stress Cancer drugs Smoking |
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Chronic Type A Gastritis
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Glandular destruction and mucosal atrophy
Affects fundus Autoimmune - antibodies against gastric glands, parietal cells, intrinsic factor Usually associated with Hashimoto's, Addison's, or vitiligo Results: Pernicious anemia (due to loss of intrinsic factor) Achlorhydria (no HCl due to parietal cell loss) |
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Chronic Type B Gastritis
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Chronic irritation due to H. pylori
Affects antrum Chronic irritation leads to eventual mucosal atrophy and metaplasia, eventual carcinoma |
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Menetrier's Disease
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Mucosal hyperplasia due to inflammation of gastric mucosa
Mucosa becomes thickened with concomitant atrophy of glands |
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What are the major types of intestinal polyps?
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Hyperplastic
Hamartomatous Inflammatory Lymphoid Adenomatous |
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Hyperplastic Polyps of Intestine
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Most common colonic polyp (90%)
Most common in 50s and 60s Due to to decreased epithelial cell turnover in bowel, resulting in accumulation of mature cells on surface Little to no risk for malignant transformation |
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Hamartomatous Polyps of Intestine
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Represent malformations of glands and stroma of epithelium, causing overgrowth of mature tissue natural to area
Little to no risk for malignant transformation Can occur sporadically or in association with Peutz-Jeghers Syndrome |
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Inflammatory Polyps of Intestine
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Also called pseudopolyps
Represent inflamed regenerating tissue surrounded by ulceration Most associated with inflammatory bowel disease |
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Lymphoid Polyps of Intestine
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Large but normal variants of intramucosal lymphoid tissue
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Adenomatous Polyps of Intestine
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Also called adenomas
Neoplastic - pre-malignant Arise from proliferative dysplasia of epithelial cells lining the colon 3 subtypes: Tubular adenoma - comprised of tubular epithelial glands Villous adenoma - villous (finger like) projections - highest risk for malignant transformation if >4cm in diameter - most common to rectum and rectosigmoid colon, usually cause gross rectal bleeding, hyperkalemia, hypoproteinemia Tubulovillous adenoma - both villous and tubular features |
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Peutz-Jeghers Syndrome
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Inherited autosomal dominant hamartomatous polyp disorder that is a familial polyposis syndrome of the entire bowel
Hamartomatous polyps Spotted melanin hyperpigmentation of lips, palms, soles Low cancer potential in polyps, but increases risk of cancer (colon and others) unrelated to polyps |
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Familial Adenomatous Polyposis
(FAP) |
Due to loss of tumor suppressor gene APC
Once polyps develop, near 100% chance of colon cancer development Develop 500-2500 polyps that carpet the colon All polyps are adenomatous |
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Gardner's Syndrome
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Form of familial adenomatous polyposis
Classic FAP polyps Benign mandible and skull tumors Epidermal cysts High risk for abnormal dentition Nearly 100% chance of polyps developing into colon cancer Autosomal dominant |
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Turcot's Syndrome
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Form of familial adenomatous polyposis
Classic FAP polyps Malignant brain tumors High risk (not quite 100%) of polyps becoming colon cancer Autosomal dominant |
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Hereditary Nonpolyposis Colorectal Cancer Syndrome
(HNPCC) |
Also called Lynch Syndrome
Autosomal dominant Due to defective DNA mismatch repair genes Associated with microsatellites Increased risk of colon and other cancers (stomach, liver, brain, prostate, skin, biliary ducts, small intestine, especially endometrium and ovary) Cancer development does not usually aris from polyps Colonic malignancies occur in multiple sites, not usually formed within or in association with adenomas |
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Colon Cancer
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Usually occurs sporadically
Most arise from adenomas (adenomatous polyps) Mechanism: AP tumor suppressor gene becomes inactivated, k-RAS (oncogene) mutated and p53 (tumor suppressor) becomes inactivated Risk factors: Excessive dietary calorie intake High refined carbohydrate diet Intake of red meat Reduced consumption of dietary fiber Symptoms: Asymptomatic until late in course Iron deficiency anemia (right sided cancers) Positive hemoccult, change in bowel habit, crampy left lower quadrant discomfort (left sided cancers) Use of NSAIDs and aspirin may be protective Any over 50 with iron deficiency anemia must be worked up Liver and lungs are preferred metastatic sites |
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Diverticular Disease
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Chronic or recurrent elevated intraluminal pressures in colon cause small areas of colon wall to form outpouchings
Most common in sigmoid colon Most common in areas where blood vessels penetrate entire bowel wall (weakened areas) 2 types: Diverticulosis Diverticulitis |
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Diverticulosis
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Diverticuli present
Blood vessels at sites of diverticuli are more exposed - often yields positive hemoccult and sometimes gross bleeding Painless Diagnosed with barium enema and Xray or colonoscopy |
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Diverticulitis
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Inflammation (due to infection) of diverticuli - complication of diverticulosis
Due to seeds, nuts, or other small objects lodging in diverticulum orifice, causing bacteria to be trapped and cause infection Lower left quadrant pain Fever Elevated neutrophils Often diarrhea (but hemoccult negative - blood vessels are blocked off) Can cause abscess formation, bowel perforation, sepsis - potentially life threatening Diagnosed with CT scan TX: ciprofloxacin and metronidazole |
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Irritable Bowel Syndrome
(IBS) |
Recurrent unpredictable bowel habits (diarrhea and/or constipation) with abdominal cramping
Exacerbated by emotional stress Thought to be due to dysregulation of enteric nervous system |
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Crohn's Disease
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Inflammatory bowel disease
Rectum usually spared Ileum usually most involved "Skip lesions" Transmural Non-caseating granulomas and aphthous ulcers Crypt abscesses Strictures, fissures, fistulas Positive string sign (thin stream of barium on Xray through diseased sections) More common in whites, Jews have highest risk Smoking is strong risk factor Moderate colon cancer risk More pain, less bleeding TX: sulfasalazine or 5-ASA, vitamin B12, metronidazole, corticosteroids, immunosuppressives |
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Ulcerative Colitis
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Inflammatory bowel disease
Begins at rectum and progresses proximally Can progress through colon to ileocecal junction Continuous lesions Mucosa and submucosa only Nongranulomatous lesions (mucosal ulcers) Crypt abscesses Pseudopolyps Lead pipe colon More common in whites and Jews, females with highest risk Smoking has protective effect High risk of colon cancer and toxic megacolon More bleeding, less pain TX: bowel rest, sulfasalazine or 5-ASA, immunosuppressives |
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What is the most common symptom of malabsorption?
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Steatorrhea (may or may not be diarrhea)
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What labs should be run for suspected malabsorption?
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Stool fat analysis
Sudan III stool stain D-xylose absorption test Schilling test |
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Sudan III Stool Stain
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Qualitatively determines if stool fat is increased
Rapid and inexpensive, but limited to screening only |
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Stool Fat Analysis
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Measures quantitatively amount of fat in stool after being fed a measured quantity
High amounts of fat indicates malabsorption Gold standard test for fat malabsorption |
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D-Xylose Absorption Test
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Patient is fed d-xylose (non-digestible sugar) and it is later measured in urine
D-xylose should be absorbed from gut, enter bloodstream, and be excreted in urine In malabsorption, only small quantities will be recovered in urine |
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Schilling Test
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Used to identify cause of vitamin B12 deficiency
Patient ingests radioactive cobalt-labeled vitamin B12 and collects urine for 24 hours Test is repeated on another day with also ingesting intrinsic factor Failure to have vitamin B12 recovery in urine in first test confirms B12 deficiency Ability to recover B12 in second test is indicative of pernicious anemia, failure indicates chronic pancreatitis, bacterial overgrowth, or disease of ileum Rarely done in US because of cost and unavailability of radio-labeled cobalamin |
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Celiac Sprue
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Affects small intestine
Malabsorption of gluten Biopsy findings: flat villi in duodenum Labs: anti-gliadin, anti-gluten, anti-endomysial Ab, anti-reticulum Symptoms: Weight loss Steatorrhea Diarrhea and bloating after wheat, rye, barley, oat ingestion Some develop dermatitis herpetiformis (papulovesicular skin lesions - treated with dapsone) Highest risk in whites Causes increased risk for development of MALT lymphoma |
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Tropical Sprue
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Malabsorption disorder
Probable infectious etiology Almost exclusively found in natives or former natives of tropical regions (especially Caribbean) Symptoms: Chronic diarrhea Steatorrhea Weight loss |
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Whipple's Disease
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Malabsorption disorder
Affects any organ, but primarily intestine, CNS, joints Etiologic agent: Tropheryma whippelii (type of Actinomyces) - gram positive Symptoms: Steatorrhea Arthralgia Fever Biopsy: PAS positive macrophages in mucosa of small intestine TX: many acceptable antibiotic regimens Sulfamethoxazole/trimethoprim (first line) Penicillin OR ampicillin OR tetracycline (second line) Any antibiotic therapy has to be administered for at least 4-6 months (preferably for one year) |
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Cholelithiasis:
Cholesterol Stone |
Due to high cholesterol that ultimately saturates the bile
Excess cholesterol precipitates out in the biliary system (usually the gallbladder) Most common type of stone in US Highest risk is fat, female, over 40, fertile |
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Cholelithiasis:
Mixed Stones |
Combination of cholesterol and bilirubin precipitant
Most common type of stone worldwide |
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Cholelithiasis:
Pigment Stones |
Stones formed from excess bilirubin
Each stone represents an accumulation of bilirubin, specifically insoluble calcium salts of bilirubin and inorganic calcium Excess bilirubin is a feature of hemolysis |
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Cholelithiasis
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Gallstones in the gallbladder
Usually asymptomatic All labs normal Must be treated surgically in those with porcelain gallbladder or Native Americans (due to increased risk of gallbladder cancer) |
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Cholecystitis
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Gallbladder infection
Fever RUQ pain Murphy's sign Elevated neutrophils and alkaline phosphatase Ultrasound findings: gallbladder wall thickening, pericholecystic fluid, gallstones |
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Choledocholithiasis
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Obstruction of common bile duct
RUQ pain Jaundice Clay colored stool Tea colored urine Elevated alkaline phosphatase and conjugated bilirubin Ultrasound finding: dilated common bile duct |
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Ascending Cholangitis
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Infection of common bile duct
Complication of choledocholithiasis RUQ pain Jaundice Clay colored stool Tea colored urine Fever Elevated alkaline phosphatase and conjugated bilirubin Elevated neutrophils Can quickly ascend to liver and cause life threatening sepsis |
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Charcot's Triad
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For ascending cholangitis
RUQ pain Jaundice Fever |
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Primary Sclerosing Cholangitis
(PSC) |
Non-infectious inflammation and sclerosis of bile ducts with eventual obliteration of all biliary ducts
Pruritis RUQ pain Jaundice Cirrhosis (later in course) Elevated conjugated bilirubin and alkaline phosphatase Highest risk: patients with IBD (especially ulcerative colitis) Unknown cause |
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Primary Biliary Cirrhosis
(PBC) |
Autoimmune destruction of intrahepatic bile ducts
Pruritis Jaundice Steatorrhea Xanthelasmas Positive AMA Elevated alkaline phosphatase and GGT Elevated bilirubin (later in course) Anti-mitochondrial antibody More common in those with CREST, Sjogren's, type I diabetes Most patients are women age 35-60 |
