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- Symptoms for rheumatic fever include
- subcutaneous plaques, polyarthritis, erythema marginatum, chorea, and carditis
- Name the characteristics of S. pyogenes
- gram (+) cocci, beta hemolytic, bacitracin sensitive, group A
- Titers of this can detect recent S. pyogenes infection
- ASO
- Most important virulence factor, determine the type of Group A, beta hemolytic strep,
- M protein
- 3 important inflammation related enzymes possessed by S. pyogenes
- hyaluronidase, streptokinase, and DNase
-
degrades hyaluronic acid, the ground substance of subcutaneous tissue, facilitates rapid spread of infection
- hyaluronidase
- converts plasminogen to plasma
- streptokinase
- degrades DNA in exudates or necrotic tissue
- DNase
- determine the group of beta hemolytic strep, located in the cell wall and its specificity determined by amino sugar
- C carbohydrate
- Toxins and hemolysins possessed by S. pyogenes
- Erythrogenic toxin, streptolysin O and S, pyogenic exotoxin A, exotoxin B
- causes rash of scarlet fever, acts as a superantigen, only produced by certain strains of S. pyogenes
- Erythrogenic toxin
- hemolysin that is inactivated by oxygenation, causes beta hemolysis when colonies grown on blood agar
- Streptolysin O
- hemolysin S, not inactivated by O2, NOT antigenic
- Streptolysin S
- Responsible for cases of TSS from S. pyogenes, same mode as Staph aureus
- Pyogenic exotoxin A
- protease that rapidly destroys tissue, produced by the "flesh-eating stains of S. pyogenes
- Exotoxin B
- Diseases caused by S. pyogenes
- Cellulitis, pharyngitis, scarlet fever, TSS, rheumatic fever, glomerulonephritis, necrotizing fasciitis
- Drugs used to treat S. pyogenes
- Penicillin G and erythromycin
- Rash that begins on trunk and spreads outward
- Sandpaper rash of scarlet fever
- Signs of poststreptococcal glomerulonephritis
-
Hematuria, hypertension, edema of face and ankles in 2-3 weeks
- pustular lesions and honey comb-like crusts after strep skin infections
- impetigo
-
Subepithelial IC deposits with granular IF; ICs activate alternative complement pathway; hematuria 1-3 weeks after infection
- Findings of poststreptococcal glomerulonephritis
- most common cause of nephrotic syndrome of children, more common in girls than boys
- minimal change disease
- Negative IF findings, fusion of podocytes and no deposits on EM
- Minimal change disease
- unlike focal segmental glomerulosclerosis, patients with this typically respond well the steroids
- minimal change disease
- most common cause of nephrotic syndrome in adults
- Membranous glomerulonephritis
- Minimal change disease typically occurs after
- immunization
- Peak incidence of minimal change disease is ages
- 2-6
- Although most cases of idiopathic (85%), other causes of membranous glomerulonephritis are
-
DISC
Drugs- (penicillamine)
Infections (hepatitis B,C, syph)
Systemic (SLE, DM)
Cancer - Light microscopy of membranous glomerulonephritis shows
- diffuse thickening of the capillary walls
- Silver stains in membraneous glomerulonephritis shows
- basement membrane projections (spikes)
- Immunofluorescence in membranous glomerulonephritis shows and electron microscopy displays
-
Granular and linear pattern of IgG and C3
Subepithelial deposits along the basement membranes with effacement of podocyte foot processes - The variable course of membranous glomerulonephritis includes
- spontaneous remission, persistent proteinuria or end-stage renal disease
- Immunofluorescence in APSGN includes
-
granular deposits of IgM, IgG and C3 throughout the glomerulus
"lumpy-bumpy" - Characteristics of nephritic syndrome
- Hematuria (RBC casts), hypertension, azotemia, oliguria, proteinuria (
- Characteristics of nephrotic syndrome
- "Leaky" basement membranes, deposits change charge allowing albumin to leak out Severe proteinuria (>3.5g) Hypoalbuminemia (
- Renal calculi occur in __% of the population
- 6
- Most renal calculi are composed of
- Calcium oxalate
- Type of kidney stones seen in gout, leukemia, and patients with acidic urine
- Uric acid stones
- Magnesium ammonium phosphate stones are associated with infection by
- urea-splitting bacteria, these stones often form large staghorn calculi
- True or false: Calcium stones are radiolucent and cannot be seen on x-ray
- False, they are radiopaque
- Spike and dome appearance
- Membranous glomerulonephritis
- Lipid accumulation in renal tubule cells
- lipoid nephrosis/ minimal change disease
- Cystine stones are almost always associated with
- cystinuria or genetically determined aminoaciduria
- Two urease positive organisms that can cause staghorn calculi are
- Proteus vulgaris and Staphylococcus
- Symptoms of UTIs are
- Urinary frequency, dysuria, pyuria, hematuria, bacteriuria
- Common causative organisms or UTIs or pyelonephritis are
- E. coli, Proteus, Klebsiella, and Enterobacterium
- Predisposing factors of developing acute pyelonephritis include
- Urinary obstruction, vesicoureteral reflux, pregnancy, urethral instrumentation, DM, BPH
- By age 60 __% of men have BPH __% of men have it by 70
- 70% and 80%; incidence increases with age
- Chapman's point for the prostate
- Along the IT band, PSIS and L5 spinous process
- The gross appearance of BPH includes
- enlarged prostate with well-demarcated nodules in the transition and central (periurethral) zones
- Microscopic appearance of BPH
- glandular and stromal hyperplasia
- Clinical signs of BPH
- decreased caliber and force of stream, trouble starting and stropping stream, postvoid dribbling, urinary retention and incontinence
- Treatment options for BPH include
- Transurethral resection of prostate (TURP), the 5-alpha reductase inhibitor, finasteride (Proscar) and the selective alpha-1 receptor blockers terazosin and prazosin
- Complications of BPH
- UTIs, urinary bladder trabeculation and diverticula formation, hydronephrosis and renal failure (rare)
- 5% of calcium oxalate stones are associated with hyperoxaluria or acquired overabsorption in pts with enteric diseases which is also seen in
- vegetarians because of their diet that is high in oxalates
- Potential inhibitors of kidney stones formation include
- diphosphonate, citrate, glycosaminoglycans osteopontin and a glycoprotein called nephrocalcin
- These stones are most hazardous because they may pass into ureters producing colic and ureteral obstruction
- small stones
- These are classified as microcytic anemia which have an MCV
-
TAILS
Thalassemia
Anemia of chronic disease - These are considered microcytic anemias which have an MCV
-
TAILS
Thalassemia
Anemia of chronic disease
Iron deficiency
Lead poisoning
Sideroblastic anemia - Causes of normocytic anemia with a low reticulocyte count
-
Ineffective erythropoiesis:
Marrow failure
Aplastic anemia
Myelofibrosis
Leukemia/Metastasis
Renal failure
ACD - Causes of normocytic anemia with a high reticulocyte count
-
Sickle cell anemia
G6PD deficiency
Hereditary spherocytosis
Autoimmune hemolytic anemia
Paroxysmal Nocturnal Hemoglobinuria - Iron panel for iron deficiency anemia
-
Serum iron: decreased
TIBC: Increased
% saturation: decreased
Serum ferritin - Iron panel for anemia of chronic disease
-
Serum iron: decreased
TIBC: decreased
% saturation: decreased
Serum ferritin: increased (iron trapped in macrophages) - Storage form of iron
- ferritin
- Form of iron precipitated in tissues in the form of degraded ferritin mixed with lysosomal debris
- hemosiderin
- dietary deficiency of iron is seen in
- elderly, children, poor
- Molecule that transports iron
- transferrin
- Clinical features of iron deficiency
- free erythrocyte protoporphyrin, epithelial atrophy if Plummer-Vinson syndrome is present, koilonychia (concave nails) and pica
- Patients with beta-thalassemia begin to show symptoms at
- 6 months- when hemoglobin F levels decline
- Erythroid hyperplasia in beta-thalassemia causes
- "crewcut" skull x-ray and increased size of maxilla (chipmunk face)
- Blood smear in patients with beta-thalassemia can show
- microcytic anemia with target cells and increased reticulocytes
- Most common cause of death in beta-thalassemia major
- Congestive heart failure
- Seen when one of the beta-globin chain genes has been damaged
- beta-thalassemia minor; asymptomatic
- Damage to Beta globin genes is mainly to due these mutations
- point
- This can result from the lifelong blood transfusions necessary for beta-thalassemia major
- Secondary hemochromatosis
- Hemoglobin electrophoresis in beta-thalassemia major shows
- increased hemoglobin F (90%) and hemoglobin A2 and decreased hemoglobin A
- Genetic disorder affecting the hexose monophosphate shunt pathway
- G6PD deficiency
- Hereditary spherocytosis is autosomal dominant or recessive?
- Dominant
- Patients with this are at increased risk of red cell aplasia due to parvovirus B19
- Hereditary spherocytosis
- Hereditary spherocytosis is typically due to a defect in
- ankyrin or spectrin of the erythrocyte membrane which causes a decrease in the erythrocyte surface membrane
- Tx for hereditary spherocytosis
- splenectomy
- Lab testing of patients with hereditary spherocytosis shows
-
Increased osmotic fragility
Normal MCH
Increased MCHC - These cells are not flexible and therefore are removed by the spleen by macrophages
- Spherocytes
- Signs of hereditary spherocytosis
-
splenomegaly
increased bilirubin
increased risk for jaundice and pigment gallstones secondary to chronic hemolysis - Formed by oxidation of hemoglobin, can be visualized with supravital stains
- Heinz bodies; eaten by splenic macrophages to form bite cell erythrocytes
- The rate limiting enzyme in the hexose-monophosphate shunt
- glucose 6 phosphate dehydrogenase
- This antioxidant is reduced in G6PD deficiency
- Glutathione; normally protects by breaking down Hydrogen peroxide
- G6PD is inherited through what pattern
- X-linked
- In african americans (A- type) with G6PD deficiency, the hemolysis is secondary to
-
acute oxidative stress such as
oxidative drugs (primaquine, sulfonamides, and anti-Tb drugs)
and viral or bacterial infections - In individual with the mediterranean type of G6PD deficiency disease is associated with
- favism due ingestion of fava beans; has more severe hemolysis because all erythrocytes have decreased G6PD activity in that there is both decreased synthesis and decreased stability
- Inflammatory mediator associated with increased hepatic production of hepcidin
- IL-6
- Effects of hepcidin on iron and rbc production
-
inhibits ferriportin function in macrophages
reduces the transfer of iron from the storage pool to developing erythroid precursors in the bone marrow - hepcidin has what effect on erythropoietin levels
- directly or indirectly suppresses
- hepcidin is structurally related to this family of peptides that have intrinsic antibacterial activity
- defensins
- Potential explanation for iron sequestration in the setting of inflammation
- enhance the body's ability to fend off certain types of infection, particularly those that require iron for pathogenicity
- Potential causative agents of aplastic anemia
- alkylating agents, chloramphenicol, chemical agents (benzene, insecticides), infection (EBV, CMV, parvovirus, hepatitis) or whole body radiation
- if present, the dx of aplastic anemia should be seriously questioned
- splenomegaly
- Signs and symptoms of aplastic anemia
-
Anemia- progressive weakness, pallor and dyspnea
Thrombocytopenia- petechiae and ecchymoses
Neutropenia- frequent and persistant minor infection or sudden onset of chills, fever and prostration - dry tap
- aplastic anemia; bone marrow often contains only fat cells, fibrous stroma and scattered lymphocytes and plasma cells
- bronze diabetes
- hemochromatosis
- Epidemiology of hemochromatosis
-
Affects males 5x more than females
common in people of Northern European descent - disease of increased levels of iron, leading to tissue injury
- hemochromatosis
- HFE is located on chromosome
- 6
- recessive disorder of the HFE gene
- primary (hereditary) hemochromatosis
- Most common mutation of the HFE gene
- C282Y mutation, increases small-intestin absorption of Fe2+
- Tx of hemochromatosis
- phlebotomy
- Dx of hemochromatosis
-
markedly elevated serum iron and ferritin or
increased tissue iron levels (Prussian blue stain) on liver biopsy -
micronodular cirrhosis
hepatocellular carcinoma (200 times the normal risk ratio)
secondary DM
hyperpigmented skin (bronzing)
CHF
cardiac arrhythmias
hypogonadism - clinical features of hemochromatosis
- Skin pigmentation in hemochromatosis is due to
- hemosiderin and melanin deposition
- autoimmune causes of aplastic anemia can be due to
- cytotoxic T cells
- most common intracorpuscular inherited hemolytic anemia observed in whites
- hereditary spherocytosis
- most common human enzyme deficiency
- G6PD
- Basophilic stippling
- thalassemias, anemia of chronic disease, iron deficiency, lead poisoning
- Fanconi's anemia
- inherited defect in DNA repair, cause of aplastic anemia
- positive osmotic fragility test in hypotonic solution
- hereditary spherocytosis
- slapped face
- parvovirus B19
- 5 most common pediatric diseases with rash:
- Measles, rubella, scarlet fever, roseola and erythema infectiosum
- Characteristic of parvovirus erythrovirus
- DNA virus, icosahedral nucleocapsid, nonenveloped, SS linear
- smallest clinically important virus
- parvovirus B19
- Fetal infection of parvovirus can cause
- severe anemia and hydrops fetalis
- reason parvovirus infects only rbc precursors not mature red cells
- only replicates when the cell is in S phase
- B19 virus infects primarily two types of cells
-
red blood cell precursors (erythroblasts) in the bone marrow, which accounts for the aplastic anemia, and
endothelial cells in the blood vessels, which accounts, in part, for the rash associated with erythema infectiosum. - Parvovirus infection in adults, especially women can cause this
- arthritis of the small joints of the hands and feet bilaterally which can resemble RA
- Findings associated with erythema infectiosum
-
bright red rash that is most prominent on the cheeks, low-grade fever, runny nose (coryza), and sore throat.
A "lacy," less intense, erythematous rash appears on the body.
Symptoms resolve in about 1 week.
- contribute to the pathogenesis of the rash and to the arthritis that is seen in some adults infected with B19 virus
- Immune complexes composed of virus and IgM or IgG
- end in -prazole
-
Proton pump inhibitors
Ome-, esome-, lanso-, rabe- - end in tidine
-
H2 blockers
Cime-, Famo-, Niza-, Rani - MOA of PPIs
- Covalently bind to and thus irreversibly inhibit the proton pump, K+/H+ ATPase
- Active form on PPIs
- thiophilic sulfonamide
- Prodrug activated metabolically in an acid dependent manner in parietal cells
- PPIs
- Clinical indications of PPIs
-
Peptic ulcers
GERD
Zollinger-Ellison syndrome - Major side effects of PPIs
-
Decreased B12 absorption due to decreased gastric acid
GI upsets
Headache, arthralgias and myopathy
Metabolized by P450 in the liver - Antibiotics used in the treatment of H. pylori
-
Amoxicillin
Bismuth
Clarithromycin
Metronidazole
Tetracycline
Usually 2-3 antibiotics are used with a PPI
ex Amox + Clarith + Omeprazole - MOA of H2 blockers
-
Suppression of Gs mediated cAMP-PKA chain reaction in parietal cells
Proton pump is inactivated leading to decreased gastric acid secretion - Clinical uses of H2 blockers
-
Peptic ulcers, GERD (alt. to PPIs)
Gastritis caused by stress
dyspepsia - H2 blocker that inhibits P450
- cimetidine
- Side effects specific to cimetidine
- gynecomastia or galactorrhea
- Side effects of H2 blockers
- Bradycardia, intestinal upset leading to diarrhea, headache, fatigue and myalgias
- all of the H2 blockers inhibit first pass metabolism of ethanol except
- famotidine
- For maximum effect, PPIs should be taken
- 30 minutes before breakfast or the largest meal of the day
- Inhibits the metabolism of warfarin, phenytoin, diazepam, and cyclosporine
- Omeprazole
- patients must be counseled to discontinue PPI therapy if they have diarrhea for several days because these drugs can cause increased
- C diff colitis
- modified form of endotoxin
-
LOS- lipooligosaccharide
contained on N. gonorrhea - Gram (-) diplococci that oxidizes glucose not maltose
- N. gonorrhea
- inactivates C3b component of complement, present in strains that disseminate
- porin protein A
- Allows N. gonorrhea to attach to mucosa and are antiphagocytic
- Pili
- yellowish-green exudate
- N. gonorrhea
- incubation time of N gonorrhea
- 2-6 days
- Media used to grow N. gonorrhea
-
Thayer-Martin
chocolate agar w/antibiotics: vancomycin, nystatin, colistin, trimethoprim - Typically symptomatic in men and asymptomatic in women
- Gonorrhea
- Tx for gonorrhea
- Ceftriaxone, erythromycin eye drops for neonates or silver nitrate
- Clinical presentations of gonorrhea
-
Urethritis, epididymis, purulent vaginal discharge and intermenstrual bleeding (cervicitis), salpingitis, anorectal infections
pharyngitis, opthalmia neonatorum - infection of the liver capsule
- Fitz-Hugh-Curtis syndrome
- Most common STD in the US
- Chlamydia
- white-clear discharge
- chlamydia
- elementary bodies
-
metabolically inactive form of chlamydia
reticulate bodies are the active form - Reiter's syndrome
-
associated with chlamydia infection, in males esp HLA-B27 patients
can't see, cant pee, cant climb a tree - Treatment for chlamydia
- Azithromycin/ tetracycline
- Stains used to visualize intracytoplasmic inclusions of chlamydia
-
iodine and Giemsa
can also culture with cycloheximide - Incubation period of chlamydia
- 2-3 wks
- ulcers, lymphadenopathy, rectal strictures
-
lymphogranuloma venereum
chlamydia serovars L1-L3 - clinical features of chlamydia trachomatis (D-K)
- urethritis, cervicitis, conjunctivitis, Reiter's syndrome, PID
- antibody dependent complement pathway
- classical; C1 binds to Fc portion of IgM or IgG
- Mannose binding protein binds sugars on the surface of pathogens and associated proteases cleave C4 and C2
- Lectin complement pathway- antibody independent
- always active at a low level, amplified when active C3 binds to a surface that lacks regulatory proteins
- Alternative complement pathway
- disrupts binding of factor B to C3b
- decay accelerating factor
- Characteristics of H. pylori
- Gram - bacilli, curved, urease +, growth on Campy agar
- What percent of duodenal and gastric ulcers are due to H. pylori
- 100% and 70%
- gastritis limited to the antrum due to H pylori can lead to
-
decreased somatostatin secretion by antral D cells, causing acid hypersecretion
risk of duodenal ulcers - gastritis that extends throughout the stomach in helicobacter pylori infections
-
acid hyposecretion causing chronic infection and inflammation
risk of gastric ulcers, gastric carcinoma - Dx of helicobacter pylori
-
14C labeled urea breath test: labeled urea ingested and labeled CO2 exhaled if bacteria urease present
biopsy
IgG titer in serum - microaerophilic spirochete, sensitive to high temperature
- treponema pallidum
- Treatment of syphilis
- penicillin G
- This can result from treatment of syphilis due to lysis of the treponeme which releases endotoxin-like factors
- Jarisch-Herxheimer reaction
- Symptoms of Jarisch-Herxheimer reaction
- fever, chills, and myalgias
- Patients with these can have a false positive VDRL test due to anti-cardiolipin antibodies
- SLE and infectious mono; clarify with FTA-ABS test
- Diseases associated with a palm and sole rash
- syphilis, coxsackievirus, and Rocky Mt. Spotted fever
- appears 6 weeks after exposure to syphilis
-
painless chancre of primary syph
due to organism multiplying at inoculation site
heals spontaneously over 6 weeks - wart-like painless lesions in moist area
- condyloma lata
- Findings of secondary syphilis
- condyloma lata, meningitis, hepatitis, arthritis, maculopapular rash on palms and soles
- visible 6 wks after syphilitic chancre heals
-
Secondary syphilis; disseminated spirochetes proliferate forming lesions throughout the body
cycle of secondary syphilis can repeat multiple times - detects anti-treponemal antibodies
- FTA-ABS; specific diagnostic test
- detects reagin antibodies against cardiolipin
- VDRL -nonspecific
- Transplacental transmission of syphilis
- congenital syphilis: stillbirth, fetal abnormalities
- CN VIII deafness, mulberry molars, saber skins, saddle nose, Hutchinsons incisors
- congenital syphilis
- accommodates of near objects but does not react to light
- Argyll-Robertson pupil
- Findings of tertiary syphilis
-
gummas
CV: aortitis, ascending aortic aneurysm
CNS: tabes dorsalis, general paralysis, meningitis, Argyll-Robertson pupil - Enveloped, DS circular DNA virus
- Hepadnaviridae Orthohepadnavirus
- antigen found in mammalian mitochondrial membranes and treponemes
- Cardiolipin; cheap source is cow heart
- benzathine penicillin
-
used for primary and secondary syphilis and close contacts
penicillin G is used for congenital and late syphilis - Dane particle
- infectous HBV
- Clinical presentation of hepatitis B
-
Acute: occasionally sever
Chronic infection: 5-10% of adults, 90% of infants
Primary hepatocellular carcinoma, cirrhosis - Fever, malaise, headache, anorexia, vomiting, dark urine, jaundice
- symptoms of hepatitis
- incubation time of hepatitis B
- 2-24 weeks
- end in thromycin
- macrolides; ery, azi, clari
- MOA of macrolides
-
Inhibit translocation of peptidyl-tRNA from acceptor to donor site (-static)
Binds to 50S subunut - Side effects of macrolides
-
Motility enhanced GI disturbances
Auditory toxicity (reversible)
Cholestatic jaundice
Cardiac arrhythmias (increase QT interval) - Clinical uses of macrolides
-
Gram (+) cocci -not MRSA
Atypical organisms (Chlamydia, Mycoplasma and ureaplasma)
Legionella
Campylobacter and helicobacter
mycobacterium avium-intracellulare (MAC)
Pertussis - Macrolides have what effect on cytochrome P450
- Inhibition
- Primary mechanism of resistance to fluoroquinolones
- change in sensitivity to inhibition of target enzymes; increased activity of transport systems that promote drug efflux
- Mechanism of resistance to macrolides
-
Active transport out of cells
Formation of methyltransferases that alter drug binding sites on the 50S ribosomal subunit - Mechanism of resistance to penicillins
-
Production of beta-lactamases which cleave the beta-lactam ring
change in penicillin binding proteins
change in porins - Quinolones are bactericidal or bacteriostatic
- bactericidal
- Fluoroquinolones end in
- -Floxacin; cipro
- MOA of fluoroquinolones
- inhibit topoisomerase II (DNA gyrase) and topoisomerase IV (responsible for separation of replicated DNA during cell division)
- Clinical uses of quinolones
- UTIs, STDs, GI infections, pseudomonal and legionella, mycobacteria, meningococcal meningitis, staph and strep
- Group 2 quinolones are most potent against
- gram (-) bacteria; cipro, en, levo
- Group 3 quinolones are most potent against
- Gram (+) bacteria; moxi, spari, gati
-
Iron and calcium limit their absorption
Reduce dose in renal dysfunction - Fluoroquinolones
- Side effects of fluoroquinolones
-
Tendonitis, tendon rupture
photosensitivity, rashes
CNS effects- insomnia, dizziness, headache
Contraindicated in pregnancy and children
Liver toxicity
Cardiac QTc interval prolongation
Elevated/decreased glucose levels in diabetics - Inhibition of DNA gyrase by quinolones is more significant than that of topoisomerase IV in
-
Gram - bacteria
the opposite is true for gram + bacteria - MOA of penicillin
-
Bind to PBPs, block the crosslink of peptidoglycan by inhibiting transpeptidase
Also activates bacterial autolytic enzymes
Bactericidal - Side effects of penicillins
-
Allergy- in the form of skin rash, Stevens-Johnson syndrome, angioedema, or anaphylaxis
Enteric disturbances
Nephritis-interstitial (methicillin)
Neurotoxicity- seizures in pts with renal failure - Clinical uses for penicillin
-
PEN SACS
Pneumococci
Enterococci
N. meningitidis
Strep and Staph
Anthrax
Actinomyces
Clostridium
Spirochetes - Very narrow spectrum, beta-lactamase resistant
-
Naficillin, methicillin, oxacillin
Used for staph (not MRSA) - Extended spectrum, antipseudomonal, beta-lactamase sensitive penicillins
-
Ticarcillin piperacillin, azlocillin
Increased activity against gram - rods including pseudomonas aeruginosa - Broad spectrum, aminopenicillins, beta-lactamase sensitive
- Ampicillin, amoxicillin
- Predisposing risk factors for developing peptic ulcers, besides H. pylori
-
NSAIDs- which causes direct chemical irritation and suppresses PG syntheses
Steroid use- suppress PG synthesis and impair healing
smoking- impairs mucosal blood flow and healing - Although more than 70% of individuals with PUD are infected with H pylori, fever than __% of H pylori infected individuals develop peptic ulcer
- 20
- Duodenal ulcers are more common in patients with
-
blood group O
MEN I
ZE syndrome
cirrhosis
COPD
chronic renal failure - classic presentation of duodenal peptic ulcer
- burning epigastric pain that 1-3 hours after eating relieved by food- WT GAIN
- Classic presentation of gastric peptic ulcers
-
burning epigastric pain, which worsens with eating
WT LOSS - Small (
- gastric peptic ulcers
- Hemorrhage, iron deficiency anemia, penetration into adjacent organs, perforation, and pyloric obstruction
- Complications of peptic ulcers
- Ranks 4th in both annual physician visits and costs among all GI diseases
- PUD
- arises most frequently in the upper and middle third of the esophagus
- Squamous cell carcinoma
- Most common after age 50, increased incidence in men, people with blood group A
- Carcinoma of the stomach
- Incidence of gastric carcinoma is higher in those geographic areas
- Japan, Finland, Iceland
- Dietary risk factors for developing gastric carcinoma
- Nitrosamines, smoked meats and fish, pickled vegetables, benzpyrene, decreased intake of fruits and vegetables and excessive salt intake
- Left supraclavicular lymph node
- Virchow node- metastasis of gastric carcinoma
- Krukenberg tumors
-
bilateral involvement of the ovaries by metastatic carcinoma of the stomach
tumor cells have abundant mucin- signet ring cells - linitis plastica
- thickened leather bottle appearance of stomach in gastric carcinoma
- Clinical findings of gastric carcinoma
-
Wt loss and anorexia
epigastric abdominal pain mimicking a peptic ulcer
early saiety and occult bleeding with iron deficiency anemia - infiltration of the stomach by poorly differentiated tumor cells, frequently numerous signet ring cells and linitis plastica
- Diffuse type of gastric carcinoma
-
polypoid (fungating) carcinoma which forms a solid mass projecting into the lumen of the stomach
high degree of association with H pylori - Intestinal type gastric carcinoma
- Most common type of esophageal cancer in the world but not in the US
- Squamous cell carcinoma
- Risk factors for squamous cell carcinoma
- heavy smoking, alcohol use, achalasia, Plummer-Vinson syndrome, tylosis and prior lye ingestion
- Treatment for gastric carcinoma
- gastrectomy; 5 year survival of 20%
-
Affects males more than females
Blacks more than whites
typical age is older than 50 - Squamous cell carcinoma of esophagus
- Progressive dysplagia, wt loss and anorexia, bleeding, hoarseness or cough
-
Clinical presentation of SCC of esophagus
often asymptomatic until late in the course - celiac sprue is associated with HLA..
- B8, DR3 and DQ
- skip lesions
- Crohns
- Most common site for Crohn's
- Terminal ileum
- Lead pipe deformity on barium study
- UC; due to loss of haustra
- Most common site for UC
- Rectum, progresses backwards
- Crohn's or UC: limited to mucosa and submucosa
- UC
- Crohn's or UC: String sign on barium study
- Crohns
- "creeping fat"
- Crohn's
- Crohn's or UC: complications include toxic megacolon and CA
- UC
- Crohn's or UC: Complications include strictures, obstruction, abscesses, fistulas, sinus tracts
- Crohns
- Common extraintestinal manifestations of both Crohn's and UC
- arthritis, spondylitis, primary sclerosing cholangitis, erythema nodosum, pyoderma gangrenosum, uveitis
- Microscopic appearance shows loss of villi, increased intraepithelial lymphocytes and increased plasma cells in the lamino propria
- Celiac sprue
- rare immune disorder that is often associated with celiac sprue
- dermatitis herpetiformis
- subepidermal blister formation with itchy, grouped vesicles and occasional bullae on the extensor surfaces
- Dermatitis herpetiformis
- granular IgA deposits at the tips of dermal papillae
- Dermatitis herpetiformis
- Routine microscopy of dermatitis herpetiformis shows
- microabscesses at the tips of dermal papillae that can lead to eventual subepidermal separation causing blister formation
- raised, erythematous, painful nodules of subcutaneous adipose tissue, typically on anterior shins
-
Erythema nodosum
Associated with granulomatous diseases and strep infection - Crohn's or UC: Bimodal distribution with peaks at ages 10-30 and 50-70
- Crohn's
- Crohn's or UC: peaks at 20-30
- UC
- Presentation of inflammatory bowel disease
- bloody diarrhea, stools with mucus, crampy lower abdominal pain or fever
- Can present with malabsorption or mimic appendicitis
- Crohn's disease
- Usually presents in childhoos with malabsorption, abdominal distention, bloating, flatulence, diarrhea, steatorrhea and wt loss
- Celiac sprue
- Tx of celiac sprue
- restriction of gluten
- Approximately 10-15% of cases lead to small intestine malignancy, most often enteropathy type T cell lymphoma
- Celiac sprue
- Crohn's or UC: crypt abscess in which there are infiltrates of neutrophils in the crypts of Lieberkuhn
- UC
- Crohn's or UC: Red granular appearance of mucosa
- UC
- Crohn's or UC: pseudopolyps, mucosal remnants of previous severe ulceration
- UC
- associated with ret gene
- MEN 2A and 2B
- Inheritance pattern of MEN syndromes
- Autosomal dominant
- Sipple's syndrome
- MEN 2A
- Wermer's syndrome
- MEN 1
- Characteristics of MEN 1
-
Parathyroid tumors, pituitary (prolactin or GH), Pancreatic (Zollinger Ellison syndrome, insulinoma, VIPomas, glucagonomas)
Commonly presents with kidney stones and stomach ulcers -
Multiple, intractable peptic ulcers in duodenum, jejunum and stomach
Gastrin levels >1000 - Zollinger-Ellison syndrome
- Sister Mary Joseph's nodule
- subcutaneous periumbilical metastasis of stomach carcinoma
- acanthosis nigricans
- features of gastric adenocarcinoma
- Spread pattern of GI tract tumor
- lymph nodes, liver, lungs
- Used for screening of celiac sprue
- tissue transglutaminase antibodies
- Autoimmune-mediated intolerance of gliadin (wheat) leading to steatorrhea
- Celiac sprue
- Celiac sprue is commonly found in people of
- Northern European descent
- Treatment of crohn's
- Corticosteroids, infliximab
- Possible etiology of Crohn's
- Disordered response to intestinal bacteria
- Primary sclerosing cholangitis
- think UC more than Crohn's
- treatment of UC
- ASA preparations (sulfasalazine), infliximab, colectomy
- 3rd most common cancer and 3rd most deadly
- colorectal cancer
- CEA tumor marker
- colorectal cancer
- autosomal dominant mutation of APC gene on chromosome 5q
- Familial adenomatous polyposis (FAP)
- Risk factors for colorectal cancer
- IBD, Strep bovis bacteremia, tobacco use, large villous adenomas, juvenile polypsos syndrome, Peutz-Jeghers syndrome, High fat diet
- Most common cause of primary hyperparathyroidism
- Adenomas (80%); can be associated with MEN I
- 15% of hyperparathyroid cases due to this
- parathyroid hyperplasia- diffuse enlargement of all four glands
- Clinical features of hyperparathyroidism
- Most asymptomatic; may cause kidney stones, osteoporosis, osteitis fibrosa cystica, metastatic calcifications or neurologic changes
- Condition that can result from chronic renal failure, vitamin D deficiency or malabsorption
- secondary hyperparathyroidism
- Causes of hypoparathyroidism
- Surgical removal of glands during thyroidectomy, DiGeorge syndrome, radiation to neck or idiopathic
- Twitching of ipsilateral facial muscles after tapping muscles
- Chvostek sign- suggestive of neuromuscular excitability by hypocalcemia
- inflating a bp cuff above systolic blood pressure for several minutes so that if hypocalcemia is present, muscular contractions, including flexion of the wrist and metacarpophalangeal joints, hyperextension of the fingers and flexion of the thumb on the p
- Trousseau sign
- Osteitis fibrosa cystica
-
von Recklinghausen's syndrome
cystic bone spaces filled with brown fibrous tissue - Autosomal-dominant kidney unresponsiveness to PTH, hypocalcemia, shortened 4th/5th digits, short stature, mental retardation
-
Pseudohyperparathyroidism
(Albright's hereditary osteodystrophy) - Lab findings in primary hyperparathyroidism
- hypercalcemia, hypercalciuria, hypophosphatemia, increased PTH and alk phos, increased cAMP in urine
- Lab findings in secondary hyperparathyroidism
- hypocalcemia, hyperphosphatemia, increased alk phos and PTH
- Perioral numbness and tingling
- sign of hypoparathyroidism
- fluke found in undercooked fish, causes inflammation of the biliary tract which can lead to pigmented gallstones
- Clonorchis sinensis
- Charcot's triad of cholangitis
- Jaundice, fever, RUQ pain
- inspiratory arrest on deep palpation
- positive Murphy's sign
- Native Americans tribes with increased incidence of cholesterol gallstones
- Pima and Navajo
- Risk factors for cholelithiasis
- 4 F's: female, fat, fertile, forty
- Pigmented bilirubinate stones are composed of
- Calcium salts and unconjugated bilirubin
- Risk factors for developing pigmented bilirubinate stones
-
chronic hemolytic anemia, cirrhosis, bacterial infection, old age and parasites
radiopaque - Cholesterol stones are associated with
- obesity, Crohn's, cystic fibrosis, advanced age, clofibrate, estrogens, multiparity, rapid weight loss and Native American origin
- Complications of cholelithiasis
- cholecystitis, biliary tract obstruction, pancreatitis, choledocholithiasis, cholangitis, gallstone ileus
- Macrovesicular fatty change that may be reversible with alcohol cessation
-
Hepatic steatosis
Gross appearance is enlarged, yellow, greasy - acute illness that usually follows a heavy drinking binge
- alcoholic hepatitis
- Microscopic changes that occur is alcoholic hepatitis
-
hepatocyte swelling (ballooning) and necrosis
Mallory bodies- eosinophilic inclusions of cytokeratin intermediate filaments -
Micronodular, irregular shrunken liver with hobnail appearance
Sclerosis around central vein
Has manifestations of chronic liver disease - Alcoholic cirrhosis- final and irreversible form of alcoholic liver disease
- AST > ALT
- alcoholic hepatitis
- most common cause of renal artery stenosis
- atheromatous plaque
- Sources of estrogen
-
ovary- 17beta-estradiol
placenta- estriol
blood- aromatization
peripheral- estrone - Estrogen or progesterone: causes cervical mucus to be thin and watery
- Estrogen; makes it easy for sperm to traverse
- Theca cells have receptors for
- LH; produce androstenedione from cholesterol which it sends to granulosa cells
- Source of progesterone
- Corpus luteum, placenta, adrenal cortex, testes
- Estrogen or progesterone: Development of genitalia and breast, female fat distribution
- Estrogen
- Granulosa cells have receptors for what
-
FSH throughout cycle
LH added late in follicular phase
produce estrogen from androstenedione - Estrogen or progesterone: stimulation of prolactin secretion but blocks its action at breast
- Estrogen
- Estrogen or progesterone: Growth of follicle, endometrial proliferation, increased myometrial excitability
- estrogen
- Estrogen or progesterone: maintenance of pregnancy
- progesterone
- Estrogen or progesterone: stimulation of endometrial glandular secretions and spiral artery development
- progesterone
- Estrogen or progesterone: decreased myometrial excitability
- progesterone
- Estrogen or progesterone: production of thick cervical mucus, which inhibits sperm entry into uterus
- progesterone
- Estrogen or progesterone: increases body temperature 0.5-1.0F
- progesterone
- Estrogen or progesterone: inhibitiion of gonadotropins (LH, FSH)
- progesterone
- Estrogen or progesterone: Uterine smooth muscle relaxation
- progesterone
- Phase of menstrual cycle that is constant 14 days
-
luteal phase
follicular can vary in length - Frequent but irregular menstruation
- metorrhagia
- heavy menstruation
- menometrorrhagia
- > 35 day cycle
- oligomenorrhea
- blood from ruptured follicle causes peritoneal irritation that can mimic appendicitis
- Mittelschmerz
- removes restraint of meiosis I prophase which oocyte has been in since fetal life; 1st polar body extruded
- LH surge
- Parts of the Graafian follicle that are ovulated
- oocyte and corona radiata
- Component that secondary follicle has but primary doesn't
- theca layer
- Components that differentiate tertiary follicle from a secondary follicle
- antrum, theca externa and interna, multiple layers of granulosa cells
- DNA content of primary oocyte
- 4N
- DNA content of secondary oocyte
- 2N
- Meiosis II is arrested in
- Metaphase until fertilization
- DNA content of ovum
- 1N, Haploid
- Fertilization more commonly occurs where
- upper end of the fallopian tube (the ampulla)
- Occurs within 1 day of ovulation
- fertilization
- Implantation occurs within how many days of fertilization
- 6
- Source of hCG
- Syncytiotrophoblast of placenta
- Maintains the corpus luteum (thus progesterone) for the 1st trimester by acting like LH
- hCG
- Components of HELLP syndrome
-
Hemolysis
Elevated LFTs
Low Platelets - HTN, proteinuria and edema in pregnancy
- preeclampsia
- Occurs in 7% of pregnant women from 20 weeks gestation to 6 weeks postpartum
- preeclampsia
- Increased incidence of preeclampsia in pts with
- preexisting HTN, DM, chronic renal disease, and autoimmune disorders
- Risk factors for preeclampsia
- prior hx, obesity, age older than 35 or younger than 18, African american race, nulliparity, multifetal pregnancy, hydratidiform mole, fetal hydrops
- Begins 1st day of menses
- Follicular phase
- If estrogen levels are still rising, this has not occurred
- ovulation
- Begins 24-36 hours before ovulation when granulosa cells become receptive (gain receptors for) LH
- luteal phase
- Etiology of preeclampsia
- placental ischemia due to impaired vasodilation of spiral arteries resulting in increased vascular tone
- Signs and symptoms of severe preeclampsia
- headache, blurred vision, abdominal pain , altered mentation, hyperreflexia, edema of face and extremities, thrombocytopenia, hyperuricemia
- Treatment of preeclampsia
-
Delivery of fetus as soon as viable
Bed rest, salt restriction, monitoring and treatment of HTN
IV mag sulfate and diazepam to prevent and treat seizures - Most common site for ectopic pregnancy
- Fallopian tubes (~90%), ovary, abdominal cavity, intrauterine portion of the fallopian tube
-
Tubal damage such as in pelvic inflammatory disease
prior ectopic pregnancy
prior tubal surgery
nonwhite race
age 35-44
current IUD
Endometriosis - Risk factors for having an ectopic pregnancy
- Signs and symptoms of ectopic pregnancy
-
Severe abdominal pain
Evidence of intra-abdominal bleeding including hypotension and collapse
Adnexal mass
Vaginal bleeding
Signs of peritoneal irritation
Absence of gestational sac on ultrasound with beta-hCG level >2500mIU/mL - Treatment of choice in ectopic pregnancy
-
Methotrexate
Contraindicated if;
hCG > 15,000mIU/mL, adnexal mass >3cm, patients hemodynamic state is unstable - Etiology of placenta previa
-
implantation by the zygote low in the uterine cavity
defective decidual vascularization, resulting from inflammation or atrophy has been implicated - Signs and symptoms of placenta previa
- Painless vaginal bleeding- generally not present until late 2nd or early 3rd trimester
- Should not be performed until diagnosis of placenta previa has been excluded
- Pelvic exam, ultrasound is most accurate at diagnosing
- Major classifications of placenta previa
-
Complete placenta previa
Partial- placenta partially covers internal cervical os - Minor classifications of placenta previa
-
marginal- placental edge reaches but does not cross internal os
low-lying placenta- lower edge reaches within 2cm of os but does not cover it - premature separation of the placenta from the uterine sidewall
- placental abruption
- Causes of placental abruption
- HTN, trauma to the abdomen, decompression of an overdistended uterus, cocaine use
-
Vaginal bleeding
Abdominal, back or uterine pain
Fetal bradycardia or late decelerations
uterine irritability, tachysystole, tetany, elevated baseline intrauterine pressure
maternal hypotension or signs of volume loss -
Signs and symptoms of placental abruption
DIC may be associated - Clinical uses of leuprolide (GnRH agonist)
-
Infertility- pulsatile
Prostate CA, uterine fibroids- continuous - Drugs that decrease the effectiveness of OCs
-
Anticonvulsants
Barbs, phenytoin, carbamazepine, toprimate
Antiinfectives
Rifampin, Griseofulvin - Common side effects of Oral contraceptives
-
Break-through bleeding (initially and later due to endometrial atrophy)
Breast Tenderness
Headache (may also treat headache)
Nausea (related to estrogen dose)
Mood Changes, change in libido
Edema - Oral contraceptives can help prevent
-
Bone loss
Fibrocystic/benign breast disease
Pelvic inflammatory disease
Ectopic pregnancy
- Cancers reduced by use of oral contraceptives
- Ovarian, endometrial, colorectal
- absolute contraindications of oral contraceptives
- Pregnancy, hx of CVA, DVT, PE, heart disease, smoking >20 cigarettes/day, migraines, current breast CA, viral hepatitis, liver disease
- primary oocyte with surrounding single layer of pregranulosa cells
- primordial follicle
- primary oocyte surrounded by a single layer of cuboidal granulosa cells
- primary follicle
- primary oocyte surrounded by several layers of cuboidal granulosa cells and theca cells
- secondary follicle
- granulosa cells closest to the oocyte secrete the mucopolysaccharides that form the
- zona pellucida- immediately surrounded the oocyte
- Most important molecular event in process of capacitation
- removal or modification of protective protein coat from the sperm cell membrane
- receptors on the plasma membrane of the sperm cell bind to___ which induces the sperm cell to undergo
- ZP3; acrosomal reaction
- Contains hydrolyzing enzymes necessary for the sperm to penetrate the zona pellucida
- acrosome
- two methods by which sperm enters zona pellucida
-
Chemical- hydrolytic enzymes in acrosome
Mechanical- oscillation of sperm head - A rise in ____ inside the oocyte triggers the ________ in which there is exocytosis of granules beneath the plasma membrane which harden the zona pellucida
- Ca2+, cortical reaction
- induces completions of the oocyte's 2nd meiotic division
- rise in intracellular Ca2+
- specialized endometrium of pregnancy
- decidua
- Oxytocin is synthesized mostly in the
- paraventricular nucleus
- stimuli for oxytocin secretion include
-
dilatation of the cervix and vagina
suckling at the breast - Which stimulates and what inhibits oxytocin release
- Estradiol, relaxin
- causes contraction of the myoepithelium that surrounds alveolar channels in the mammary gland
- oxytocin
- stimulates the frequency and force of contraction
- oxytocin
- OC effects on clotting time possibly due to
- increase in factors VII, VIII, IX and X and a decrease in antithrombin III
- Beta0 mutations
- absent beta-globin synthesis
- beta+ mutations
- reduced but detectable beta-globin synthesis
- Most common cause of beta+ thalassemia
- splicing mutations
- Most common cause of Beta0 thalassemia
- Chain terminator mutations- create stop codon or frameshift
- Individuals with two beta-thalassemia alleles (B+/B+, B+/B0, B0/B0) have a severe transfusion depended anemia called
- thalassemia major
- heterozygotes with one beta thalassemia gone and one normal gene (B+/B, B0/B) have a mild asymptomatic microcytic anemia called
- beta thalassemia minor
- Loss of which tumor suppressor genes are involved in developing SCC of esophagus
- p53 and p16/INK4alpha
- Most common cause of small bowel obstruction
- adhesions after abdominal surgery
- second most common cause of SBO
- incarceration of a groin hernia
- Pain associated with small bowel obstruction may be
-
crampy and intermittent
periumbilical or diffuse - Clinical features of small bowel obstruction
-
Abdominal pain
Vomitus in proximal obstruction
Constipation
Abdominal tenderness, distention
tympanic to percussion
high pitched bowel sounds - Should make one suspect bowel gangrene, intra-abdominal abscess or peritonitis
- leukocytosis or >20,000/mm3 or left shift
- Leukemia of pts newborn to 14 years old
- ALL
-
Patient 15 to 39 years old
pts 40-60 - AML
- leukemia of patients over 60 years old
- CLL
- Most common overall leukemia
- CLL
- leukemia in pts 40-60 yrs old
- CML
- t9:22 translocation of ABL proto-oncogene
-
Chronic myelogenous leukemia (CML)
proto-oncogene fuses with the break cluster region (BCR) in chromosome 22 - Splinter shaped to rod shaped structures in the cytosol of myeloblasts
- Auer rods- NOT present in CML
-
Leukemia that is most common in middle aged men
Type of B cell leukemia - Hairy cell leukemia
- Lab findings in hairy cell leukemia
-
pancytopenia
leukemic cells have hair-like projections
positive tartrate-resistant acid phosphatase stain (TRAP) - Only leukemia without lympadenopathy
- Hairy cell
- Numerous smudge cell (fragile leukemic cells)
- Chronic lymphocytic leukemia
- HLA alleles seen in almost all people with celiac disease
- HLA-DQ2 and DQ8
- There is an association of celiac disease and other immune diseases including
- type 1 diabetes, thyroiditis, Sjogren syndrome as well as ataxia, autism, depression, some forms of epilepsy, IgA nephropathy, Down and Turner syndrome
- Most common celiac disease associated cancers
- enteropathy associated T cell lymphoma and small intestine adenocarcinoma
- inhibits the secretion of penicillins by competing for active tubular secretion via the organic acid transporter and, thus, can increase blood levels
- probenecid
-
drug is effective against many of the same organisms as penicillin G; therefore, it is used in patients who are allergic to the penicillins.
- erythromycin
- methylation of an adenine in the 23S bacterial ribosomal RNA causes
- a decreased affinity for the 50S ribosomal for macrolides
- Interference with the metabolism of drugs such as theophylline and carbamazepine has been reported in
- clarithromycin- possibly other macrolides
- distributes well to all body fluids except CSF
- erythromycin
- the antibiotic eliminates a species of intestinal flora that ordinarily inactivates digoxin, thus leading to greater reabsorption of the drug from the enterohepatic circulation
- Macrolides
- A synthetic progestin employed in combination oral contraceptive preparations is
- norgestimate
- connective tissue cells in the outermost layer of the follicle that make collagen
- theca externa cells
-
Compared with healthy pregnancies, in cases of pre-eclampsia and miscarriage the ratio of Foxp3(+) Treg to IL-17-expressing CD4(+) T cells is:
A. not significantly different
B. increased
C. decreased
- decreased
-
While vertical transmission can occur at any stage of syphilis, the highest transmission rate occurs in which stage?
- secondary stage
- The thick colostrum secreted initially after a birth has high concentrations of:
- immunoglobulins and lactoferrin
- the superior parathyroid glands develop from
- endoderm of pharyngeal pouch 4
- RL is a 40-year-old male who suffers from Crohn's disease, which is currently in remission. Which of the following dietary recommendations is most appropriate for him at this time?
- low fat
- persistent lymphocytic infiltrate in liver biopsies > 6 months
- definition of chronic viral hepatitis
- A common site of obstruction of a ureteral calculus is:
- at the intramural passage through the bladder wall
-
Baby's head stretches cervix
Cervical stretch excites fundic contraction
Fundic contraction pushes baby down and stretches
cervix some more
Cycle repeats over and over again - Theory for the onset of intensely strong contractions during labor
-
True or false: abdominal contractions
add greatly to the force that causes expulsion of
the baby. - True; Once uterine contractions become strong during labor, pain signals originate both from the uterus itself and from the birth canal. These signals elicit neurogenic reflexes in the spinal cord to the abdominal muscles, causing intense contractions of these muscles.
- Besides prolactin, estrogen and progesterone, what hormones are needed for the secretion of milk
- insulin, growth hormone, cortisol and parathyroid hormone
- Effects of parathyroid hormone
-
Increased Ca2+ reabsorption in the early distal tubule
Decreased phosphate reabsorption in the proximal tubule
Decrease reclamation of bicarbonate in the proximal tubule
Increases bone resorption
Stimulated by hypocalcemia and hyperphosphatemia -
Technetium-99m-sestamibi radionuclide scan
- Dx for primary hyperparathyroidism