Stuff You Missed II Flashcards
Three important metabolic pathways for glucose
- Glycolysis and TCA cycle - used to generate ATP. Glucose is first metabolized to pyruvate during glycolysis and then pyruvate is converted to acetyl-COA, which enters TCA cycle
- Glycogenesis stores glucose for later use avia formation of glyogen from GLUCOSE-1 PHOSPHATE
- HMP shunt (pentose pathway) generate pentose sugars and NADPH
Oxidative portion of HMP shunt
- Is irreversible
- Rate limiting enzyme: Glucose 6 phosphate dehydrogenase (G6PD)
GLUCOSE-6-PHOSPHATE is converted to RIBULOSE-5-PHOSPHATE which results in NAPDH formation.
-
Non-oxidative portion of HMP shunt
- Is reversible
- key enzyme is TRANSKETOLASE (B1 dependent)
- Used to convert sugars to ribose-5-phosphate (for nucleotide synthesis) and intermediates (fructose 6 phosphate and glyceraldehyde-3-phosphate) for glycolysis and gluconeogeneis
-
Discuss NADPH and Glutathione
NADPH (made in oxidative part of HMP shunt) reduces glutathione, a co-enzyme for gluthathione peroxidase which prevents oxidative damage by converting H2O2 into H2O
Where is the oxidative phase of HMP shunt most active?
In tissues that use NADPH in reductive pathways
- Adipose tissue for fatty acid sythesis
- Adrenals for steroid synthesis
- Glutathione reduction in RBC
- Liver for fatty acid and steroid synthesis
Glucose 6 Phosphate Dehydrogenase Deficiency
- X-linked recessive disease with predominance in Asia, Mediterranean, Africa (malaria resistance countries)
Hemolytic anemia when RBCs are exposed to oxidative stress because they lack sufficient NADPH production thus less glutathione activity
Causes of oxidative stress
Can be dangerous in case of glucose 6 phosphate dehydrogenase
- Infections
- Fava beans (“broad beans”)
- Drugs (e.g. sulfonamides, dapsone, primaquine)
Describe peripheral smear of patient with Glucose 6 Phosphate Dehydrogenase
RBCs have Heinz bodies (intracellular inclusions composed of denatured hemoglobin)
- Also contain degmacytes (bite cells) - result of splenic macrophages removing Heinz Bodies
Hepatocellular Carcinoma - Presentation
Liver mass with increased alpha fetoprotein
- associated with HBV
- integration of viral DNA into host cellular genome is trigger for neoplastic changes
- HBx activates IGF-2 and IGF-1 to stimulate cell proliferatin
- HBV also suppresses p53 tumr suppressor, leading to accumulations of mutations in hepatocytes leading to carcinogenesis
Risk factors for Hepatocellular Carcinoma
- HBV and HCV
- Alcoholic Cirrhosis
- Alfatoxins
- Hemochromatosis
Anal fissure
tear in lining of canal DISTAL to dentate line that occurs most often on posterior midline.
- Patients complain of severe tearing pain associated with passage of bowel movements
- Associated with low-fiber diets and constipation
Parietal cells
release H+ ions into gastric lumen via H/K ATPase , which requires ATP hydrolysis thus active transport mechanism
Omeprazole
suppress activity of gastric parietal cell H/K/ATPase leading to an increase in pH of gastric lumen
Lidocain
Local anesthetic
- Class IB antiarrhythmic agen that blocks voltage gated Na channels in sensory neurons, Purkinje fibers, and ventricular cells
Dofetilide
Class III (K+ blocker) that blocks passive transport of potassium, in cardiomycocytes leading to prolongation of refractory period and QT interval
Pancreatic divism
incomplete fusion of ventral and dorsal pancreatic buds. Usually asymptomatic, but may predispose to acute or recurrent pancreatitis.
- No duodenal obstruction
Annular pancreas
Due to abnormal migration of ventral pancreatic bud which encircule the duodenum and may lead to sx of duodenal obstruction in neonates
Zenker’s diverticulum
- due to cricopharyngeal muscle dysfunction caused by diminished relaxation of pharyngeal muscles during swallowing
- Found in upper esophagus
- classically older patients presenting with oropharyngeal dysplasia, coughing, choking, and recurrent aspiration
True diverticula (of esophagus)
Due to scarring and traction of esophagus.
- Seen in midportion of esophagus and result from mediastinal lymphadenitis (TB, fungal infections)
Intussusception
occurs in children younger than 2 and in region of ileocecal valve
- presents with intermitten, severe, colicky abdominal pain, “currant jelly” still and possible palpable mass in RUQ
Fever, jaundice, anorexia in IV drug user
Suggests viral hepatitis (likely caused by Hep C)
- acute viral hepatitis causes hepatocyte apoptosis and necrosis
Effects of viral hepatitis on hepatocytes
- Apoptotic hepatocytes shrink, undergo nuclear fragmentation and become intensely eosinophilic
- Eosinophilic bodies called Acidophillic bodies, Councilman bodies, and apoptotic bodies
Hep A presentation in children
Commonly silent or subclinical (“anicteric”) in children but can present as an acute ilnness characterized by jaundice, malaise, nausea, vomiting, and RUQ pain
Thiamine (B1) is a co-factor for which 3 important enzymes?
- Transketolase (in nonoxidative HMP shunt)
- Alpha ketoglutarate Dehydrogenase (Alpha ketoglutarae to Succinyl-CoA) in TCA cycle
- Pyruvate Dehydrogenase (Pyruvate –> Acetyl-CoA)
Co-factors needed for Alpha Ketoglutarate Dehydrogenase
- Thiamine
- Lipoic Acid
- CoA
- FAD
- NAD
Areas most susceptible to ischemia with ischemic colitis
- SPLENIC FLEXURE (lies between SMA and IMA)
2. DISTAL SIGMOID COLON (lies between IMA and hypogastric arteries)
Salmonella Typhi
- causes typhoid or enteric fever
- faculative intracellular parasite orally, penetrates intestinal mucosa and travels to mesenteric lymph nodes where it is phagocytosed by macrophages for survival
- characterized by fever, abdominal pain, diarrhe, and “rose spots”
Pseudomonas Aeruginosa
- produces enterotoxin A, similar to diptheria toxin that halts human cellular protein synthesis by inhibiting EF-2
- Arrest in translation as protein chain is unable to change positions in ribosome
Vibrio cholerae
- causative agent of cholera and produces exterotoxin, CHOLERAGEN
- Choleragen acts like heat-labile toxin of ETEC in that increases cAMP in intestinal mucosal cells leading to decreased absorption and increased secretion of Na, Cl, and water
C. difficile
- produces toxin A (enterotoxin) and toxin B(cytotoxin) and causes pseudomembranous colitis
- mostly seen in patients recently treated with antibiotics
Toxin B of C. difficile
Depolymerizes actin filaments causing GI mucosal cells death
Enterohemorrhagic E. coli (EHEC) toxin
- produces Shiga-like toxins (aka Vero cytotoxins)
- identical to Shiga toxin produced by Shigella dysenteriae
- toxins inhibit 60S ribosomal subunits thus blocking protein synthesis by preventing binding of tRNA
Right sided colon cancer vs. Left sided colon cancer
Left sided colon cancers manifest as partial intestinal obstruction (because right sided colon has larger lumen)
Right sided colon cancers present with symptoms of iron deficiency and systemic symptoms
Gastroduodenal artery
Lies along posterior of duodenal bulb (1st part of duodenum). It is more likely to be eroded by posterior duodenal ulcers.
- Ulceration into the gastroduodenal artery is source of life-threatening hemorrhage
Brown pigment gallstones
- Arise secondary to infection of billiary tract which in turn releases B-glucuronidase by injured hepatocytes and bacteria
- B-glucoronidase hydrolyzes bilirubin glucuronides and increases amt of uncojugated bilirubin in bile
Infections associated with brown pigment gallstones
E. coli
Ascaris lumbricoides
Liver Fluke (Opisthorichis sinesis)
Populations associated with brown pigment stones
- Rural Asian populations
- Women
- Elderly
7-alpha hydroxylase
Converts cholesterol to bile acids. Deficiency leads to cholesterol gallstone
First order kinetics (of Pharmocology)
Same PROPORTION of drug is metabolized per unit of time - thus linked to drug concentration
(e.g. For 20 mg dose of Drug X, 10mg will be metabolized in hour. For 40 mg of Drug X, 20 mg will be metabolized in 1 hr)
Zero order kinetics (of Pharmacology)
Same AMOUNT of drug is metabolized independent of drug dose
- If 30 mg of drug Y was administered, 10 mg will be metabolized in one hour.
- If 60 mg of drug Y was administered, 10mg will be metabolized
What slows progression of hemochromatosis in women?
Physiological iron loss through menstruation and pregnancy
Sx of hemachromatosis
- Micronodular cirrhosis
- Diabetes mellitus
- Skin pigmenation
- Cardiac dysfunction due to accumulation of Fe in myocardium
- Hepatomegaly
- Cardiomegaly
CREST
C-alcinosis R-aynaud Syndrome E-sophageal dysmotility S-clerodactly T-elegienctasia
Early sign of systemic sclerosis
Esophageal dysmotility and incompetence of lower esophageal sphincter
- Result of atrophy and fibrous replacement of esophageal muscles
- Esophageal dilation causes reflux, increases risk of Barrett’s esophageus and esophageal adenocarcinoma
C. difficile toxins
Toxin A - attracts neutrophils to cause mucosal inflammation, loss of water in the gut, and diarrhea
Toxin B - causes actin depolymerization, loss of cytoskeleton integrity, cell death, and mucosal necrosis
Colon adenocarcinoma
- Rectosigmoid colon - most common location
- Often present with obstructing glands
Colon adenocarcinoma: Pathology
Consist of pleomorphic cells with large dark nuclei forming irregular crowded glands, some of which contain mucus
Gallstone ileus
results from passage of large gallstone (>2.5 cm) throug cholecystenteric fistula into small bowel causing obstructing to ileocecal valve.
Gas within gallbladder and biliary tree on abdominal X-ray suggests what?
Presence of cholecystenteric fistula to small bowel as intestinal gas can now enter gallbladder.
-Predisposes gallstone ileus
TPN-induced gallstone
- Biliary stasis from absent enteral stimulation due to decreased CCK release
- In those with ileal resection, disturbance of bile acid circulation results in supersaturation of hepatic bile with cholesterol
Antibodies directed against HCV envelope proteins don’t confer immunity because?
HCV envelope proteins vary their antigenic structure, thus production of host antibodies always lag behind the mutant strains and thus immunity is not given
Sx of adult lead poisoning
- Colicky abdominal pain, constipation, impaired concentration
- Bluish pigmentation at gum-line
- Wrist drop due to peipheral neuropathy
- MICROCYTIC Anemia and Basophilic stippling
Stages of Lead Poisoning (Hint: 4)
- Nausea, diarrhea, and abdominal pain. Hemorrhage, Hypovolemia, and Shock.
- GI symptoms resolve and patient appears better
- Metabolic acidosis, Hepatitic dysfunction, and Hypoglycemia
- Scarring of recovering GI tract
Cholestasis can cause malabsorption of which vitamins?
Fat soluble vitamins (e.g. A,D,E, K)
- Osteomalacia may result of poor Vitamin D absorption
Cholestasis
- can arise secondary to hepatocellular dysfuncton and intrahepatic or extrahepatic biliary obstruction
Esophagus (on CT)
Found between vertebral bodies in upper thorax and the trachea (remains open). It is typically collapsed and invisible on CT.
Are gastric ulcers from peptic ulcer disease seen on distal duodenum?
No. They are typically found on antrum, pyloric area of stomach or in first part of duodenum
Zollinger- Eilison Syndrome
Occurs to hypersecretion of gastrin by cardiac tumor.
- Gastrin increases gastric acid production whcih causes peptic ulcers.
- Diarrhea is common symptom in Z-E as excess gastric acid inactivates pancreatic enzymes
Pantothenic Acid (Vitamin B5)
- Needed form coenzyme A, essential for aceylation reactions
- Binds with oxaloacetate in first step of TCA to form citate and then succinyl-CoA
Sx of Carcinoid syndrome
- Flushing
- Asthma-like symptoms (wheezing, dyspnea)
- Diarrhea
- Syncope (low blood pressure)
Carcinoid syndrome
- Sign of GI metastesis
- Associated with appendiceal tumors which secrete active substances like serotonin
- If tumor is localized to GI tract, liver clears serotonin before any systemic symptoms can appear
Ondansetron
potent anti-emetic mainly used in patients undergoing chemotherapy. Selectively blocks 5-HT3 receptors.
Treatment of Carcinoid Syndrome
Octeotride - somatostatin analog that can inhibit secretion of many hormones and horomone-like substances
Secretin
- produced S cells in the DUODENUM
- stimulates Bicarb production in pancreas
Secretin release stimulated by what?
Excess HCl
Hepatocyte injury in viral hepatitis
- Diffuse swelling termed “balloow dengerating”
Hepatocyte death characterized by lobular architecture disruption and hepatocyte necrosis called “bridging fibrosis
-Presence of mononuclear inflammation
Common side effects for nitrates
Headaches and cutaneous flushing due to vasodilation caused by nitrates (including nitroglycerin and isosorbide)
Common cause of mitral regurgitation in undeveloped countries
Rheumatic fever
Strep viridans and adherence during subacute endocarditis
S. viridans - normal oral cavity inhabitans
- Dextrans produced by S. viridans with sucrose as substrate facilitate bacterial adherence and colonization to fibrin
- MUST HAVE PRE-EXISTING DAMAGE
S. aureus vs. Strep viridans in endocarditis
S. aureus can adhere to INTACT/ NON-DAMAGED endothelium to cause endocarditis
S. viridans can only attach to ALREADY DAMAGED valvular leaflet to cause endocarditis
Genetic mutation in Hypertrophic cardiomyopathy
Due to defect in cardiac sarcomere proteins. Most common defect is is Beta-myosin heavy chain
Dilated cardiomyopathy
Majority cases are due to autosomal dominant mutaitons of cardiac myocyte cytoskeletal proteisns (dystrophin) or mitochrondrial enzymes
Sx: of coarctation of aorta
Diminished femoral pulses compared to brachial pulses, symptoms of inadequate perfusion of lower extremities
Genetic syndrome associated with Coarctation of Aorta
Turner’s Syndrome
Cardiac defect in Down Syndrome
Endocardial Cushion Defects (Ostium primum ASD, regurgitant atrioventricular valves)
Cardiac defect in DiGeorge Syndrome
Tetralogy of Fallot and interrupted aortic arch (truncus arteriosus)
Cardiac defect in Friedrich’s ataxia
Hypetrophic cardiomyopathy
Cardiac defect in Marfan’s Syndrome
Cystic medial necrosis of the aorta
Cardiac defect in Tuberous Scleross
Valvular obstruction due to cardiac rhabdomyoma
Most likely cause of fatigue and new-onset murmur in young adult
Bacterial endocarditis. Acute, diffuse, proliferative glomerulonephritis secondary to circulating immune complexes may complicate BE and result in renal insufficiency
Long term hemodynamic compensatory response to volume overload of Aortic Regurgitation
Increase in left ventricular preload (LV end-diastolic volume) in associated with ECCENTRIC left venticular hypertrophy
Concentric hypertrophy of the LV
Response to pressure overload, involves in PARALLEL deposition of sarcomeres which results in wall thickening and decreased EDV
Cyanotic neonate with severe tachypnea and continuous machine like murmur
ECG shows aorta that lies anterior to and to the right of pulmonary artery
Transposition of Great Arteries
Transposition of Great Arteries
Failure of aorticopulmonary septum to spiral normally during fetal development.
- Result is aorta is connected to right ventricle and pulmonary artery is connected to left ventricle
- Only VSD, PDA, or ASD allows this to be compatible with lidfe
Number Needed To Treat
1/ Absolute Risk Reduction
Absolute Risk Reduction
(No disease/ Total receiving placebo) - (No disease/ Total receiving treatment)
Sx: Atrial Myxoma
- Constitutional symptoms
- Mid-diastolic rumbling murmur heard at apex (mitral stenosis)
- Large penduculated mass in LA
Atrial Myxoma
Tumor compoed of scattered cells with mucopolysaccharide stroma, abnormal blood vessels, and hemorrhaging
Patient presents with hx of malabsorption complains of pruritic skin rash over extensor surfaces of arms.
Dermatitis herpetiformis
- associated with celiac disease
- erythematous, puritic papules, vesicles, bullae that appear over extensor surfaces
Treatment for acute gouty arthritis
NSAIDs, Colchicine
Colchicine
- affects tubulin polymerization into microtubules which disrupts chemotaxis and phagocytosis
- associated side effects: nausea, abdominal pain, and diarrhea
Caudal regression syndrome
characterized by sacral agenesis causing lower extremity paralysis and urinary incontinence
- associated with poorly controlled maternal diabetes
Cocaine abuse on fetus
- Due to vasocontrictive effect, can cause insufficient blood flow to fetus, results in spontaneous abortion, intrauterine growth retardation, placental abruption, and/or prematurity
Congenital effect of rubella
- Can cause mental retardation and congenital heart defects
Congenital effects of Vitamin A overdose
Craniofacial abnormalities
Posterior fossa CNS defects (Arnold-Chiari syndrome??)
- Auditory defects
- Abnormalities of great vessels (similar to DiGeorge)
Iron deficiency during pregnancy
Can restrict fetal growth
- important in 2nd half of pregnancy when maternal blood volume expands a lot
PTH effects on calcium and phosphate
- increases serum calcium level
- mediates bone resorption by causing osteoBLasts to inc. production of RANK-ligant and M-CSF to stimulate osteoCLasts
- decreases serum phosphate (loss in urine)
Manifestations of sickle cell disease
- HEMOLYSIS - repeated sickling of RBCs to leads to permanent sickling and premature erythrocyte destruction
- VASOOCCLUSIVE symptoms: pain from small bone or bone marrow infarctions in hand, feet, wrist, and ankles (dactylitis)
- INFECTIONS - predisposed to encapsulated organisms due to repeated splenic infarcts
Dactylitis
- Painful swelling of hands and feet
- common vasooclusive presentation of sickle cell anemia in young children
Hemolysis and haptoglobin levels
In hemolysis, haptoglobin levels decrease by binding to free hemoglobin and the complex is hepatically cleared
Raloxifene
Selective Estrogen Receptor Modulator (SERM)
- binds to estrogen receptors and exhibits tissue-specific behavior that antagonize natural estrogen effects
- IN BONE, acts like estrogen AGONIST and inhibits osteopeross
Effects of raloxifene in breast vs. bone
In breast, raloxifene is an estrogen ANTAGONIST thus useful treatment for estrogen-positive breast cancer
In bone, raloxifene is an estrogen AGONIST and inhibits osteoporosis
Markers for osteoblast activity
Bone-specific osteoblastic activity
Markers for osteoclast activity
- Tartrate-resistant acid phosphatase
- Urinary hydroxyproline
- Urinary deoxypyridinoline (most reliable)
Vitamin D analogs and Psoriasis
Vitamin D analogs (calcipotriene, calcitrol, and tacalcitol) are used to treat psoriasis
Calcipotriene, Calcitriol, Tacalcitol
- Vitamin D analogs, can be used to treat psoriasis
- bind to Vitamin D receptor (bind and inhibit KERATINOCYTE PROLIFERATION and stimulate KERATINOCYTE differentiation
Ustekinumab (Stelara)
human monoclonal antibody used to treat psoriasis by targeting IL-12 ad IL-23
- Inhibits differentiation of CD4+ Th1 and Th17 cells
Cyclosporine
- inhibits NFAT (nuclear factor of activated T cells) from entering nucleus and modulating transcription activity by impairing production and relaese of IL-2 thus inhibiting T-cell proliferation
Keloid formation
- result from excessive collagen formation
- present as soft/firm nodules BEYOND borders of wound with “claw-like” extensions into normal tissue
- composed of large disorganized collagen bundles and excess cellular connective tissue
Most likely diagnosis
- young athlete in 20s with nodular and comedonal acne
- Likely from anabolic steroid (e.g. methyltestosterone) use. Androgens stimulate epidermal follcular epidermal hyperproliferation and excessive sebum leading to acne
Elements of pathophysiology of acne (hint: 4)
- Follicular epidermal hyperproliferation
- Excessive sebum production
- Inflammation
- Propionibacterium
Reiter’s syndrome (reactive arthritis) triad
- Urethritis
- Conjunctivitis
- Arthritis
- associated with HLA-B27
- seen weeks after a GU or GI infection
- may be seen with sacroillitis
Lentigos
-small brown/tan macules seen in sun exposed skin of elderly person
RBC cell extravasations
Petechiae (< 5mm)
Purpurae (5mm to 1cm)
Echymoses (> 1 cm)
Telangiectasias
- small permanent dilations of superficial capillaries and venules
- usually found on skin or mucous membranes
- blanch under pressure
Achondroplasia
- autosomal dominant disease due to mutation of FGFR-3
- patients present with normal spine length but short arms and legs with normal sized head
- issue with endochrondrall ossification (long bones) not membranous ossification (flat bones)
Supraspinatous muscle
- assists in abduction of arm and stablization of glenohumeral joint
- tendon is commonly injured of rotator cuff muscles
- commonly injured due to impingement of acromion and head of humerus`
Infections associated with reactive arthritis
Chlamydia Campylobacter Salmonella Shigella Yersinia
Skeletal muscle contraction
- Ca from SR binds to TROPONIN C to uncover binding sites on actin
- Myosin (energized by ATP+Pi) binds to actin
- Once myosin is bound, Pi is released which changes myosin head conformation and causes power stroke
- After power stroke, ATP binds myosin head causing myosin detachment from actin
- ATP hydrolysis (ATP –> ADP+Pi) energizes myosin for next contraction
Smooth muscle contraction
- Ca (Sarcoplasmic Reticulum OR ECF) binds to calmodulin to activate myosin-light chain kinase
- Phosphorylated MLCK more likely to bind with actin
- *Unphosphorylated MLCK has low affinity for actin. Actin is NOT covered up)
- As long as Ca is present, MLCK will stay bound to actin
- Ca-ATPase will remove Ca once stimulus is over
Treatment for male pattern baldness
Finasteride (5-alpha-reductase) inhibitor because male pattern baldness involves 5-alpha reductase and androgenic effects of dihydrotestosterone
Mitochondrial myopathy
Patients present with Neuromuscular lesions
Ragged red skeletal muscle fibers, and
Lactic acidosis
- Mitochondrial disorder thus follows maternal inheritence
Why do mitochondrial defects cause lactic acidosis?
Mitochondria responsible for OXPHOS.
No mitochondria = No OXPHOS thus presence of lactic acidosis
Heteroplasmy
Variable clinical expression of mitochondrial DNA defects in different family members due to co-existence of mutated and wild type mitochondrial genomes in each cell
Possible structures damaged during injury to mid-shaft of humerus
Radial nerve
Deep brachial artery
** Supracondylar fractures associated with injury to brachial artery
Physical findings of rickt
- Unmineralized osteoid matrix
- Widened osteoid seams
- Bowed legs
- Rachitic rosary (prominence at costevertebral junction)
- Harrison’s sulci (indentations in lower ribs)
- Craniotabes
- Growth retardation
Paget’s disease of bone findings
- mosaic of lamellar bone, irregular sections of lamellar linked by “cement lines”
- local osteoclastic activity followed by increased osteoblastic activity
- formation of abnormal bone
- new collagen is laid haphazardly
Common fracture sites in osteoporosis
- Primarily involves trabecular bone
- patients might present with fractures in lumbar vertebrae (mostly trabecular) or in neck of femur (50% trabecular/50% cortical)
Osteoporosis
represents loss of “total bone mass” that results in trabecular thinning.
-common fracture sites are: lumbar vertebrae and neck of femur
Leprosy
- caused by Mycobacterium lepare
- deforming infection of skin and nerves
- associated with armadillo contact in SW U.S.
- severity depends on strength of cell-mediated immune response, with tuberculoid leprosy and lepromatous leprosy (more severe form)
African patient presents with patchy areas of skin anesthesia and hypopigmentation in upper extremities. Microscopy shows bacteria invading Schwann cells. Likely diagnosis?
Leprosy (Hansen’s disease)
- caused by Mycobacterium leprae
Measles virus
enveloped, non-segmented, negative sense RNA virus
causes Rubeola
Measles (Rubeola)
- caused by measles virus (paramyxovirus)
- Kolik spots (white/blue-gray lesions on buccal mucosa that precede maculopapular rash
- Cough
- Coryza
- Conjunctivitis
- vaccine given at 12-15 months
Mneumonic for Measles Diagnosis
"CCCK" C-oryza C-ough C-onjunctivitis K-olik spots (white/blue-gray spots on buccal mucosa)
Rotavirus symptoms
Upper respiratory infection followed by diarrhea
Xanthelesma
- eyelid papule or plaque containing lipid-laden macrophages
- occur in primary or secondary hyperlipidemia
- Biliary cirrhosis is potential cause of hyperlipidemia
Cutaneous manifestations of HYPERthyroidism
- Thinning hair
- Pretibial myxedema
- Alopecia areata
- Hyperhidrosis
Side effects of hydrochlorothiazide
HyperGLUC
HyperGlycemia
HyperLipidemia
HyperUricemia
HyperCalcemia
** can be used for women who have osteoporosis and hypertension
Wound contractures
- Due to excessive metalloproteinase activity and myofibroblat accumulation in wound margins
- Contracture produce wound deformities and surrounding tissues esp in palms, soles, anterior thorax, or serious burn sites
Erythema infectiosum (fifth disease)
- caused by parvovirus B19 and is transmitted commonly via respiratory route
- Sx include bright-red rash on cheeks (“slapped cheeks”) and lace-like rash on trunk and extremities
Hand and foot mouth disease
- caused by Coxsackie virus type A
- presents with dever and ulcers on tongue and oral mucosa
- maculopapular and/or vesicular rash on palms and soles
Scarlet fever
- caused by Group A Strep (Strep pyogenes)
- present with fever, sore throat, diffuse erythematous rash with small papules (“sandpaper-like”)
Ecthyma gangrenosum
- cutaneous necrotic injury associated with Pseudomoans aeroginosa bacteremia and septicemia
- P. aeruginosa invades perivascularly and releases exotoxins causing vascular destruction and resultant insufficiency of bloof to patches of skin which become edematous and necrose
Populations susceptible to P. aeruginosa
- Neutropenic patients
- Hospitalized patients
- Patients with burns and chronic indwelling catheters
Dystonia
- prolonged, repetitive muscle contractions
- may be result of impaired function of ganglia
- most common types of focal dystonia are cervical dystonia (spasmodic torticolis), blepharosparm, and writer’s crap
Myoclonus
sudden, brief sometimes serve (shock-like) muscle contraction
- associated with hiccups or hypnic jerks (when falling asleep)
Pathological myoclonus is seen in epilepsy and Creutfeldt-Jakob disease
Lepromin skin test
Tuberculoid patients will have positive test because they exhibit strong CD4+ Th1 cell-mediated immune response to M.leprae
- Leprematous leprosy (more severe form) will have negative test because they exhibit weak immune response
Dantrolene
- relax skeletal muscle by reducing release of Ca from SR
- used to treat malignant hyperthermia
Succinylcholine
- depolarizing NMJ blocker administered during intubation and induction
- can be augmented by neostigmine (anti-cholinesterase) during phase I block
- can be reversed by neostigmine during phase II block
- paralysis caused by succinylcholine depends on catabolism by plasma cholinesterase
Digital clubbing
- “drumstick” sign at end of fingers
- sign of prolonged hypoxia
- often accompanies large lung-cell cancer, tuberculosis, cystic fibrosis, bronchiectasis and suppurative lung diseases (e.g empyema and chronic lung abcesses)
Androgenetic alopecia
- most common cause of hair loss in both males and female
- demonstrates polygenic inheritance with variable penetrance`
Common condition affected by multiple genes
- Androgenetic alopecia
- Epilepsy
- Ischemic heart disease
- Schizophrenia
- Glaucoma
- Hypertension
Myasthenia gravis
- autoimmune disease that results in decrease in acetylcholine receptors on post-synaptic terminal of muscle end plate
- results in decreased ability of ACh to bind and open post-synaptic cation channels, thus decreasing end-plate potential
Treatment of myasthenia gravis
- involves cholinesterase inhibitors, immunosuppresants, and somtimes thymectomy
- cholinesterase inhibitors can be improved by antimuscarinics (e.g. scopolamine) to counter muscarinic overstimulation in sites like gut without affecting skeletal muscle function
Apocrine glands
- found in breast areolae, axillae, genital regions of humans
- secrete sweat into hair follicle instead of directly to skin surface
- innervated by sympathetic fibers and not functional until puberty
- secretions odorless until bacterial decomposition
Eccrine glands
- also called merocrine glands
- present in skin throughout most of body except areas like skin and glans pens
- secrete water fluid rich in Na and Cl (think CF!!) directly to skin surface
Isoretinoin
- treats severe acne refractory to topical therapies via interaction with RAR
- main adverse effects: hypertriglyceridemia and teratogenicity
What test must be administered before giving isoretinoin to a young female?
Must give pregnancy test (test for B-hCG) because isoretinoin can cause birth defects?
Sx of Dermatomyositis
- Gottron papules - flat topped plaques over bony prominences
- Heliotrope rash - “racoon eyes”
- Proximal muscle weakness, difficulty standing or rising up from chair
- Anti-Jo 1 positive
- elevated CK levels
Telomerase
- enzyme that posesses reverse transcriptase (RNA-dependent DNA polymerase) activity and is normally expressed in stem cells as well as cancer cells
- adds TTAGGG to 3’ end of DNA
- Cancer cells continue to divide without aging and shortening telomeres
Gout
results from deposition of monosodium rate in joints and soft tissues
- underpolarized light, appear needle shaped and negatively birefringent
Psoriasis
- salmon colored plaque covered with silvery scale
- common areas include elbows, knees, gluteal cleft, lumbosacral area
- may have yellow-brown discoloration on nails with associated pitting, thickening, or crumbling
Long thoracic nerve injury
- commonly caused by mastectomy but any trauma or surgery in axillary area can damage this nerve
- damage to this nerve causes “winged scapula” and inability to abduct shoulder past 90 degrees
Rheumatoid arthritis
- swelling in pain, swelling, and morning stiffness for > 6 months
- tends to get better as day progresses
Tx for rheumatoid arthritis
Short term therapy: glucocorticoids (quick and effective)
Long term therapy: Methotrexate (used for moderate to severe rheumatoid arthritis)
Hematogenous osteomyelitis
- predominantly seen in children and affects long bones
- caused by Staph. aureus
- sx: include malaise, fevers, and pain over long bones
- Bone pain caused by abscess within bone leading to periosteal disruption and bone necrosis
Moraxella cararrhalis
- normal flora of upper respiratory tract of healthy adults and children
- causes otitis media and sinusitis in healthy ppl
- responsible for bronchitis and pneumonia in elderly patient with COPD
Sciatic nerve
L4 - S3
- splits into tibial nerve and common peroneal nerve
Tibial nerve
- inverts and plantarflexes foot
- when not working, the foot is everted and dorsiflexed (opposite of common peroneal nerve)
provides sensation to plantar aspect of foot
Most abundant amino acid in collagen
Glycine
- appears ever third amino acid position
as collagen formula is (-Gly-X-Y)333
Essential amino acid for formation of collagen alpha helix
Proli
Septic arthritis
- usually due to gonococcus infection, common cause of infection in your adults
- suspect if affected joint has high WBC count but absent crystals
- ## requires immediate treatment (e.g. ceftriazone) to prevent joint destriction, osteomyelitis, and sepsis
Bacteroid species
Gram - anaerobic rods
- areas of necrosis and diminished blood supply (e.g. chronic non-healing ulcers) facilitate growth of anaeroes
- produce B-lactamase, which breaks down peniccilin
B-lactamase inhibitors
Tazobactam
Clavulanic acid
Sulbactasm
- most effectie against most gram - enteric rods, including Pseudomonas aeruginoise and Bacteroides fragilis
Trauma or sustained pressure to neck of fibula causes injury to what nerve
- Common peroneal nerve ( as it runs around neck of fibula)
- susceptible to traima from lateral blows of knee to tightly applied plaster casts
Migratory thrombophlebitis
- should always think cancer
- hypercoagulability is very common paraneoplastic syndrome seen in adenocarcinomas of pancrease, colon or lug
- adenocarcinomas produce thromboplastin-like substance capable causing chronic intravascular coagulations
Cachexia
syndrome that encompasses anorexia, malaise, anemia, weight loss and generalized wasting due to underlying systemic disease.
TNF-alpha is a cytokine that causes necrosis of some tumors in utero
- Inhibitig
IVC
formed by union of right and left common illiac veins at level of L4-L5
- Renal arteries lie at L1
Apoptosis
can occur either the intrinsic (mitochondria-mediated) pathway or extrinsic (receptor-initiated) pathway.
- Both pathways require activation of caspases that cleave cellular proteins
Foamy urine
- caused by proteinuria/ Heavy proteinuria (e.g. nephrotic syndrome) can caused interstitial edema because of decrease in serum albumn
Migratory thrombophlebitis
- should always think cancer
- hypercoagulability is very common paraneoplastic syndrome seen in adenocarcinomas of pancrease, colon or lug
- adenocarcinomas produce thromboplastin-like substance capable causing chronic intravascular coagulations
Auer rods
deformed azurophilic granules found in cytoplasm of myeloblasts that stain positively for MYELOPEROXIDASE
- found in abundance in AML M3
Paroxysmal Nocturnal Hemoglobinuria
Triad: hemolytic anemia, hypercoaguable state, pancytopenia
- causes thrombosis
- deficiecy of CD55 and 59 which disallows complement activation
Migratory thrombophlebitis
- should always think cancer
- hypercoagulability is very common paraneoplastic syndrome seen in adenocarcinomas of pancrease, colon or lug
- adenocarcinomas produce thromboplastin-like substance capable causing chronic intravascular coagulations
Migratory thrombophlebitis
- should always think cancer
- hypercoagulability is very common paraneoplastic syndrome seen in adenocarcinomas of pancrease, colon or lug
- adenocarcinomas produce thromboplastin-like substance capable causing chronic intravascular coagulations
Hereditary spherocytosis
autosomal dominant condition that results form red blood cell cytoskeletaon abnormalities
- most commonly spectrin and ankrin defects
- definitive test: positive osmotic fragility test
Tx for hyperlipidemia
Niacin (Vitamin B3) - decreases synthesis of hepatic triglyceride and VLDL by suppressing release of FA from peripheral tissues
- also decreases VLDL conversion to LDL, thus decreasing LDL
- also increases HDL
Bile-acid binding resins
can cause constipation and abdominal bloating (potentiall worsening diverticulosis), hypertriglyceridemia, cholesteral gall stone and vitamin K malabsorption
Factor V Leiden mutation
causes factor Va resistance to inactivation by activated protein C, may account for approximately 20% of cases in atypcial venous thrombosis
Sx of hereditary spherocytosis
anemia, reticulocytosis and increased indirect bilirubin, indicating hemolytic anemia
- MCHC (increased because of mild dehydration of red blood cell)
- blood smear dysmorphic red cells with no central pallor
Henoch-Schonlein purpura
- seen in young boys (3 - 10 years old)
- palpable skin lesions associated with abdominal pain, arthralgias, and renal involvement
- occurs due to deposition of Ig-A containing immune complexes and shows up in purpura on buttocks, legs
Glioblastoma multiforme
- pallisading tumor cells around areas of necrosis
- commonly crosses midline (“butterfly distribution”)
- most common primary brain tumor in adults
AML (M3 variant)
- associated with Auer rods
- t(15;17) which codes for chimeric PML/RAR (retinoic acid receptor)
- this inhibits differentiation of myeloblasts and triggers development of APML
Selective COX-2 inhibitors
e. g. celecoxib
- have no effect on platelet aggregation and cause little GI irritation
- the reduced risks of GI bleeding are only advantages over traditional NSAIDS
Microangiopathic hemolytic anemia
- associaed with RBC fragments, Burr cells, and helmet cells
- in patients with prosthetic valves, RCs are exposed to excessive shear and turbulence in circulation causing damage
Glomangioma
- very tender small red-blue lesion under nail bed
- originates from modified smooth muscle cells that control thermoregulatory functions of dermal glomus bodies
Sx: “Mismatched V/Q with perfusion defect, sudden onset chest pain
Signs of pulmonary embolism
- often caused by deep vein thrombosis and continuum of pulmonary thromboembolism
Bile acid-binding resins (cholestyramine, colestpiol, colesevelam)
- bind to bile acid in GI tract, interfereing with its enterohepatic circulation
- LDL is decreased b/c hepatic cholesterol is consumed in re-sythesis of bile acids
- since bile is being re-synthesized, cholesterol content of bile increases thus increased risk of gallstone
Bcl-abl
- associated with CML
- result of t(9;22) - Philadelphia chromosome
C-myc overexpression
- associated with Burkitt’s lymphoma
- associated with t(8;14)
- myc oncogene on chr 8
- Ig heavy chain on chr 14
Bcl-2 overexpression
- associated with Follicular lymphoma
- associated with t(14;18)
- Bcl-2 has anti-apoptotic effects
Greater activity against Factor Xa and Thrombrin.
Unfractionated heparin or LMWH
Unfractionated heparin - contains pentasaccharide that binds to antithrombin causing confirmational change that increases ability to inactivate Factor Xa
- is able to bind to both antithrombrin and thrombrin to allow antithrombrin to inactivate thrombrin
Effect modification (of study)
- is present when effect of main exposure on outcome is modified by presence of another variable. Effect modificatiion is not a bias.
Atherosclerosis
initiated by repetitive ENDOTHELIAL cell injury, which leads to chronic inflammatory state in underlying intima of large elastic arteries as well as large and medium-size elastic arteries
CML vs. leukemoid reaction
- both have increased WBC count
- differentiated based on neutrophil alkaline phosphatase level
- in leukemoid reaction (decreased alkaline phosphotase)
- in CML: decreased alkaline phosphatase
Causes of isolated systolic hypertension
- caused by age-related decrease in compliance (increased stiffness) of the aorta and its proximal major branches
Discuss protein C deficiency and Warfarin therapy
Transient pro-coagulant/anti-coagulant imbalance is present at start of warfarin therapy , leading to relative hypercoaguable state with thrombotic occlusion of microvasculature and skin necrosis
Sx: urinary urgency, nocturia, and hesistancy associated with constant back pain in elderly main
- Suggestive of metastatic prostate cancer
- Prostate cancer likes to metastasize to bone
Prostate cancer
- adenocarcinomas in PERIPHERAL zone of gland (vs. periurethral zone of gland in BPH)
- increased levels of PSA
- in advanced disease, may see elevated prostatic acid phosphatase (tumor penetrates capsule) and increase alkaline phosphatase
Discuss obstructive sleep apnea and EPO secretion
Obstructive sleep apnea - recurrent episodes of aphyxia during sleep
- peritubular cells in renal cortex sense hypoxia and release EPO which increases hematocrit
Ovarian cancer
- presents as ovarian mass
- possible amenorrhea
- associated with CA-125
- risks of cancer decreased by OCP, multiparity, and breast feedings
Factors which decrease ovarian and/or endometrial cancers
** Things that decrease the number of ovulatory cycles
Multiparity
OCP use
Breastfeeding
Sx of hemorrhagic cystitis
- can be result of nitrogen mustard based chemotherapeutic agent (e.g. cyclophosophamide or ifosfamide)
- metabolized by kidneys into ACROLEIN, which toxic to uroepithelial cells and cause renal cell death and necrosis
Tx for hemorrhagic cystitis due to nitrogen mustard based chemotherapeutic agents
Mesna, a sulfhydryl compound that binds acrolein in urine
Osler-Weber-Rendu syndrome
autosomal dominant condition marked by telangiectasias in skin as well as in mucous membranes of lips, oranonasopharynx, respiratory tract, GI, and urintary tract
- may cause epitaxis, GI bleeding or hematuria
Tx of DVT in pregnant women
Heparin
- increases antithrombrin III activity
** Cant use Warfarin because it’s teratogenic
Clopidogrel
inhibits ADP mediated platelet aggeregation
used in treatment of coronary artery disease, peripheral vascular disease and cerebrovascular disease NOT DVT
Tx for diabetic ketoacidosis
Intravenous hydration with normal saline and insulin
- This will result in serum glucose, osmolality, and potassium as increases in serum HCO3 and sodium
Phentolamine
Phenylephrine
- selective alpha adrenerigc agonist. Administation may be associated with reflect bradycardia
Isoproterenol
non-selective Beta adrenergic agonist that stimulates both B2 receptors vascular smooth muscle (vasodilation) and cardiac B1 (increases in cardiac rate and contractility)
Epinepherine (effect on systolic blood pressure, HR, and diastolic blood pressure)
Systolic BP: increases (alpha 1 and B 1) HR: increases (B1) Diastolic BP: (dose-dependent) Low dose - B2 > a1 (decrease) High dose - a1 > B2 (increase)
Cachexia
syndrome that encompasses anorexia, malaise, anemia, weight loss and generalized wasting due to underlying systemic disease.
TNF-alpha is a cytokine that causes necrosis of some tumors in utero
- Inhibitig
IVC
formed by union of right and left common illiac veins at level of L4-L5
- Renal arteries lie at L1
Tx for hyperlipidemia
Niacin (Vitamin B3) - decreases synthesis of hepatic triglyceride and VLDL by suppressing release of FA from peripheral tissues
- also decreases VLDL conversion to LDL, thus decreasing LDL
- also increases HDL
Discuss protein C deficiency and Warfarin therapy
Transient pro-coagulant/anti-coagulant imbalance is present at start of warfarin therapy , leading to relative hypercoaguable state with thrombotic occlusion of microvasculature and skin necrosis
Factors which decrease ovarian and/or endometrial cancers
** Things that decrease the number of ovulatory cycles
Multiparity
OCP use
Breastfeeding
Propranolol
non-selective beta adrenergic antagonist
effect on B2: vasoconstriction
effect on B1: slows heart contractility
Cachexia
syndrome that encompasses anorexia, malaise, anemia, weight loss and generalized wasting due to underlying systemic disease.
TNF-alpha is a cytokine that causes necrosis of some tumors in utero
- Inhibitig
IVC
formed by union of right and left common illiac veins at level of L4-L5
- Renal arteries lie at L1
Explain relationship between blood flow and resistance
Blood flow is directly proportional to vessel radius raised to fourth power.
Resistance to blood flow is inversely proportional to vessel radius raised to fourth power.
Cystic medial degeneration
- myxomatous changes in media of large arteries which development of aortic dissections and aortic aneurysms
Cachexia
syndrome that encompasses anorexia, malaise, anemia, weight loss and generalized wasting due to underlying systemic disease.
TNF-alpha is a cytokine that causes necrosis of some tumors in utero
- Inhibitig
IVC
formed by union of right and left common illiac veins at level of L4-L5
- Renal arteries lie at L1
Li-Fraumeni syndromee
- autosomal dominant disorder caused by inherited mutation of p53
Cyclin D1 overexpression
- associated with Mantle lymphoma
- associated with t(11;14)
Migratory thrombophlebitis
- should always think cancer
- hypercoagulability is very common paraneoplastic syndrome seen in adenocarcinomas of pancrease, colon or lug
- adenocarcinomas produce thromboplastin-like substance capable causing chronic intravascular coagulations
Fatty streaks
- multiple yellow spots approx 1mm in diam
- earliest lesion of atherosclerosis and present in all people > 10 y.o
- composed of lipid filled foamy cells and smooth muscle cells that have engulfed lipoproteins
- occurrence and location in child don’t predict locations of plaques later on in lide
Factor Xa inhibitors
- new class of anticoagulants with activity against factor Xa
- increase prothrombrin and aPTT times but don’t affect thrombrin time
Schilling test
- helps differentiate between dietary defiency of vitamin B12, pernicious anemia, and malabsorption syndromes
** Low absorpton of cobalamin not correctable by IF means malabsorptive syndrome such as ileal disease, pancreatic insufficiency, or bacterial overgrowth
Sx of steroid abuse
erythrocytosis
abnormal testicle size and function
hepatic abnormalities
acne
Strong evidence of lymph node malignancy
Monoclonal lymphocytic proliferation, esp. monoclonal T-cell receptor gene arrangements
Polyclonal proliferation of lymphocytes
associated with benign lymph node enlargement in response to antigenic stimulation
Sx of lead poisoning
- erythrocyte basophillic stippling
- microcytic anemia
Net filtration pressure
(Gh - Bh) - (Go - Bo)
von Willebrand disease
- causes impairments in platelet function and coagulation pathway abnormalities.
- associated with prolonged bleeding time
- prolonged PTT
- decreased platelet aggregation in response to ristocetin
Polycythemia vera
clonal myeloproliferative disease in pluripotent stem cells
- increased RBC mass, inc. plasma volume and low EPO
- majority have JAK2 V617F mutation, rendering RBCs more sensitive to growth factors
Strawberry hemangioma
benign vascular tumors of childhood
- appear during first few weeks of life, initially grow rapidly, then regress by 5-8 years old
- composed of capillaries separated by connective tissue
Alpha adrenergic agonists
- increase both systolic and diastolic blood pressure via stimulation of a-1 adrenoreceptors
- elevated systemic blood pressure is associated with reflex increase in vagal influence on heart, results in decreased heart rate
Vascular reaction to endothelial and intimal injury (e.g. atherosclerosis)
Intimal hyperplasia and fibrosis, predominantly mediated by reactive smooth muscle cells that migrate from media to the intima
Nitroprusside
- agent of choice in treating hypertensive emergency
- quick onset of action and short duration of action
- initially metabolized to cyanide , with conversion to thocyonate by liver rhodanase
Treatment for nitroprusside toxicity
Na thiosulfate used to treat cyanide toxicity and works by donating sulfur to liver rhodamase to enhance conversion of cyanide to thiosulfate
Likely diagnosis:
necrotizing vasculitis of upper and lower respiratory tract (nasal ulcerations, sinusitis, hemoptysis) and rapidly progressive Wegners
- Wegner’s granulomatosis (granulomatous with polyangitis)
- cANCA
Tx for familial hyoalphalipoproteinemia
- low HDL thus increased risk of CAD
- Niacin (B3) is best treatment
Tx for hypercholesteremia
Statins and ezetimbe
- High LDL is a risk factor for atherogenesis
Ezetimbe
- tx of hypercholestermia
- decreases LDL by inhibiting cholesterol absorption from GI tract
- does not increase HDL concentrations
- used in combo with statins to achieve greater LDL reduction
Statins
- treatment of hypercholesteremias by inhibiting HMG CoA reductase, rate limiting enzyme of cholesterol syntehsis
- in response hepatocytes, INCREASE expression of LDL receptors
ApoB
apoprotein present in VLDL and LDL
- decreases in VLDL and LDL will cause apolipoprotein to decrease
Discuss energy expenditure in fatty acid oxidation vs. glycolysis in cardiac function
- More energy needed for fatty acid oxidation than glycolysis
- inhibition of fatty acid inhibitors promote oxygen effiency and decreases oxygen needed for cardiac support
Energy for sources of cardiac function
- Glycolysis
- Glucose oxidation
- Fatty acid synthesis
Main source of energy production in cardiac function
Fatty acid oxidation > Glucose oxidation > Glycolysis
Varicose veins
- caused by incompetent calves in lower extremities allow retrograde blood flow from deep to superficial veins
- increases pressure in superficial veins –> dilated veins
Orthostatic hypotension
- defined as fall > 20 mmHg in systolic pressure or >10 mm Hg in diastolic pressure
Describe events to correct normal physiological “orthostatic hypotension”
- Decreased venous return to heart
- Decreased ventricular filling and drop in CO and BP
- Drop in BP evokes compensatory baroreceptor reflect (increased sympathetic activity and decreased PS activity)
- Increased sympathetic tone raises peripheral vascular resistance via ALPHA-1 of peripheral vasculature. Leads to venous return and CO
Understimulaion of alpha adrenoreceptorss
- leads to cerebral hypoperfusion (light headedness and syncope
Sinus venosus
forms smooth portion of right atrium
Bulbus cordis
forms smooth portions of right and left ventricles
Primitive atrium
forms rough portions of left and right atrium
ductus arterious
derived from 6th embryonic aortic arch
Tertiary syphillis
- can result in thoracic aortic aneurysm
- compresses adjacent structures and dilates aortic valve ring, a murmur and mediastinal widening is heard
- aneurysm begins with vaso vasorum endarteritis and obliteration resulting in inflamation
FTA-ABS
specific test for syphillis
Gemfibrozil and fenofibrate (Fibric acid derivatives)
- first line treatments for hyperTRIglyceridemia
- decrease serum triglycerides by reducing hepatic triglyceride production
Bile acid resins (e.g. cholestyramine, colestpiol, colesevelam) and effect on triglycerides
- increase triglycerides
Niacin (Vitamin B3) used to treat…
hyperlipidemia
Side effects: cutaneous (flushing, warmth, itching) - better tolerated in slow release preparations
Capsaicin
- reduces pain by decreasing substance P in the peripeheral nervous system
Buerger’s disease
- seen in heavy cigarrete smokers < 35 years old
- associated with intradermal injection of tobacco extracts
- thrombosing vascultis extends into contiguous veins and nerves, encasing them in fibrous tissue
Polyarteritis Nodosa
- segmental, transmural, necrotizing inflammation of medium to small sized arteries in any organ
- typically affects kidney, liver, heart, and GI tract but NOT LUNGS!!
- sx: livedo reticularis, palpable purpura, hemorhage, ischemia
Henoch-Schonlein purpura
- seen in young boys (3 - 10 years old)
- palpable skin lesions associated with abdominal pain, arthralgias, and renal involvement
- occurs due to deposition of Ig-A containing immune complexes and shows up in purpura on buttocks, legs
Glioblastoma multiforme
- pallisading tumor cells around areas of necrosis
- commonly crosses midline (“butterfly distribution”)
- most common primary brain tumor in adults
AML (M3 variant)
- associated with Auer rods
- t(15;17) which codes for chimeric PML/RAR (retinoic acid receptor)
- this inhibits differentiation of myeloblasts and triggers development of APML
Selective COX-2 inhibitors
e. g. celecoxib
- have no effect on platelet aggregation and cause little GI irritation
- the reduced risks of GI bleeding are only advantages over traditional NSAIDS
Sx: “Mismatched V/Q with perfusion defect, sudden onset chest pain
Signs of pulmonary embolism
- often caused by deep vein thrombosis and continuum of pulmonary thromboembolism
C-myc overexpression
- associated with Burkitt’s lymphoma
- associated with t(8;14)
- myc oncogene on chr 8
- Ig heavy chain on chr 14
Greater activity against Factor Xa and Thrombrin.
Unfractionated heparin or LMWH
Unfractionated heparin - contains pentasaccharide that binds to antithrombin causing confirmational change that increases ability to inactivate Factor Xa
- is able to bind to both antithrombrin and thrombrin to allow antithrombrin to inactivate thrombrin
Cystic medial degeneration
- myxomatous changes in media of large arteries which development of aortic dissections and aortic aneurysms
Ovarian cancer
- presents as ovarian mass
- possible amenorrhea
- associated with CA-125
- risks of cancer decreased by OCP, multiparity, and breast feedings
Factors which decrease ovarian and/or endometrial cancers
** Things that decrease the number of ovulatory cycles
Multiparity
OCP use
Breastfeeding
Sx of hemorrhagic cystitis
- can be result of nitrogen mustard based chemotherapeutic agent (e.g. cyclophosophamide or ifosfamide)
- metabolized by kidneys into ACROLEIN, which toxic to uroepithelial cells and cause renal cell death and necrosis
Osler-Weber-Rendu syndrome
autosomal dominant condition marked by telangiectasias in skin as well as in mucous membranes of lips, oranonasopharynx, respiratory tract, GI, and urintary tract
- may cause epitaxis, GI bleeding or hematuria
Tx for diabetic ketoacidosis
Intravenous hydration with normal saline and insulin
- This will result in serum glucose, osmolality, and potassium as increases in serum HCO3 and sodium
Phentolamine
Phenylephrine
- selective alpha adrenerigc agonist. Administation may be associated with reflect bradycardia
Isoproterenol
non-selective Beta adrenergic agonist that stimulates both B2 receptors vascular smooth muscle (vasodilation) and cardiac B1 (increases in cardiac rate and contractility)
Epinepherine (effect on systolic blood pressure, HR, and diastolic blood pressure)
Systolic BP: increases (alpha 1 and B 1) HR: increases (B1) Diastolic BP: (dose-dependent) Low dose - B2 > a1 (decrease) High dose - a1 > B2 (increase)
Propranolol
non-selective beta adrenergic antagonist
effect on B2: vasoconstriction
effect on B1: slows heart contractility
Treatment for nitroprusside toxicity
Na thiosulfate used to treat cyanide toxicity and works by donating sulfur to liver rhodamase to enhance conversion of cyanide to thiosulfate
Likely diagnosis:
necrotizing vasculitis of upper and lower respiratory tract (nasal ulcerations, sinusitis, hemoptysis) and rapidly progressive Wegners
- Wegner’s granulomatosis (granulomatous with polyangitis)
- cANCA
Tx for familial hyoalphalipoproteinemia
- low HDL thus increased risk of CAD
- Niacin (B3) is best treatment
Tx for hypercholesteremia
Statins and ezetimbe
- High LDL is a risk factor for atherogenesis
Ezetimbe
- tx of hypercholestermia
- decreases LDL by inhibiting cholesterol absorption from GI tract
- does not increase HDL concentrations
- used in combo with statins to achieve greater LDL reduction
Statins
- treatment of hypercholesteremias by inhibiting HMG CoA reductase, rate limiting enzyme of cholesterol syntehsis
- in response hepatocytes, INCREASE expression of LDL receptors
ApoB
apoprotein present in VLDL and LDL
- decreases in VLDL and LDL will cause apolipoprotein to decrease
Discuss energy expenditure in fatty acid oxidation vs. glycolysis in cardiac function
- More energy needed for fatty acid oxidation than glycolysis
- inhibition of fatty acid inhibitors promote oxygen effiency and decreases oxygen needed for cardiac support
Energy for sources of cardiac function
- Glycolysis
- Glucose oxidation
- Fatty acid synthesis
Main source of energy production in cardiac function
Fatty acid oxidation > Glucose oxidation > Glycolysis
Varicose veins
- caused by incompetent calves in lower extremities allow retrograde blood flow from deep to superficial veins
- increases pressure in superficial veins –> dilated veins
Orthostatic hypotension
- defined as fall > 20 mmHg in systolic pressure or >10 mm Hg in diastolic pressure
Describe events to correct normal physiological “orthostatic hypotension”
- Decreased venous return to heart
- Decreased ventricular filling and drop in CO and BP
- Drop in BP evokes compensatory baroreceptor reflect (increased sympathetic activity and decreased PS activity)
- Increased sympathetic tone raises peripheral vascular resistance via ALPHA-1 of peripheral vasculature. Leads to venous return and CO
Understimulaion of alpha adrenoreceptorss
- leads to cerebral hypoperfusion (light headedness and syncope
Sinus venosus
forms smooth portion of right atrium
Bulbus cordis
forms smooth portions of right and left ventricles
Primitive atrium
forms rough portions of left and right atrium
ductus arterious
derived from 6th embryonic aortic arch
Tertiary syphillis
- can result in thoracic aortic aneurysm
- compresses adjacent structures and dilates aortic valve ring, a murmur and mediastinal widening is heard
- aneurysm begins with vaso vasorum endarteritis and obliteration resulting in inflamation
FTA-ABS
specific test for syphillis
Gemfibrozil and fenofibrate (Fibric acid derivatives)
- first line treatments for hyperTRIglyceridemia
- decrease serum triglycerides by reducing hepatic triglyceride production
Bile acid resins (e.g. cholestyramine, colestpiol, colesevelam) and effect on triglycerides
- increase triglycerides
Niacin (Vitamin B3) used to treat…
hyperlipidemia
Side effects: cutaneous (flushing, warmth, itching) - better tolerated in slow release preparations
Capsaicin
- reduces pain by decreasing substance P in the peripeheral nervous system
Buerger’s disease
- seen in heavy cigarrete smokers < 35 years old
- associated with intradermal injection of tobacco extracts
- thrombosing vascultis extends into contiguous veins and nerves, encasing them in fibrous tissue
Polyarteritis Nodosa
- segmental, transmural, necrotizing inflammation of medium to small sized arteries in any organ
- typically affects kidney, liver, heart, and GI tract but NOT LUNGS!!
- sx: livedo reticularis, palpable purpura, hemorhage, ischemia
Cachexia
syndrome that encompasses anorexia, malaise, anemia, weight loss and generalized wasting due to underlying systemic disease.
TNF-alpha is a cytokine that causes necrosis of some tumors in utero
- Inhibitig
IVC
formed by union of right and left common illiac veins at level of L4-L5
- Renal arteries lie at L1
Apoptosis
can occur either the intrinsic (mitochondria-mediated) pathway or extrinsic (receptor-initiated) pathway.
- Both pathways require activation of caspases that cleave cellular proteins
Explain relationship between blood flow and resistance
Blood flow is directly proportional to vessel radius raised to fourth power.
Resistance to blood flow is inversely proportional to vessel radius raised to fourth power.
Foamy urine
- caused by proteinuria/ Heavy proteinuria (e.g. nephrotic syndrome) can caused interstitial edema because of decrease in serum albumn
Auer rods
deformed azurophilic granules found in cytoplasm of myeloblasts that stain positively for MYELOPEROXIDASE
- found in abundance in AML M3
Paroxysmal Nocturnal Hemoglobinuria
Triad: hemolytic anemia, hypercoaguable state, pancytopenia
- causes thrombosis
- deficiecy of CD55 and 59 which disallows complement activation
Hereditary spherocytosis
autosomal dominant condition that results form red blood cell cytoskeletaon abnormalities
- most commonly spectrin and ankrin defects
- definitive test: positive osmotic fragility test
Tx for hyperlipidemia
Niacin (Vitamin B3) - decreases synthesis of hepatic triglyceride and VLDL by suppressing release of FA from peripheral tissues
- also decreases VLDL conversion to LDL, thus decreasing LDL
- also increases HDL
Bile-acid binding resins
can cause constipation and abdominal bloating (potentiall worsening diverticulosis), hypertriglyceridemia, cholesteral gall stone and vitamin K malabsorption
Factor V Leiden mutation
causes factor Va resistance to inactivation by activated protein C, may account for approximately 20% of cases in atypcial venous thrombosis
Sx of hereditary spherocytosis
anemia, reticulocytosis and increased indirect bilirubin, indicating hemolytic anemia
- MCHC (increased because of mild dehydration of red blood cell)
- blood smear dysmorphic red cells with no central pallor
Microangiopathic hemolytic anemia
- associaed with RBC fragments, Burr cells, and helmet cells
- in patients with prosthetic valves, RCs are exposed to excessive shear and turbulence in circulation causing damage
Glomangioma
- very tender small red-blue lesion under nail bed
- originates from modified smooth muscle cells that control thermoregulatory functions of dermal glomus bodies
Bile acid-binding resins (cholestyramine, colestpiol, colesevelam)
- bind to bile acid in GI tract, interfereing with its enterohepatic circulation
- LDL is decreased b/c hepatic cholesterol is consumed in re-sythesis of bile acids
- since bile is being re-synthesized, cholesterol content of bile increases thus increased risk of gallstone
Bcl-abl
- associated with CML
- result of t(9;22) - Philadelphia chromosome
Li-Fraumeni syndromee
- autosomal dominant disorder caused by inherited mutation of p53
Bcl-2 overexpression
- associated with Follicular lymphoma
- associated with t(14;18)
- Bcl-2 has anti-apoptotic effects
Cyclin D1 overexpression
- associated with Mantle lymphoma
- associated with t(11;14)
Effect modification (of study)
- is present when effect of main exposure on outcome is modified by presence of another variable. Effect modificatiion is not a bias.
Atherosclerosis
initiated by repetitive ENDOTHELIAL cell injury, which leads to chronic inflammatory state in underlying intima of large elastic arteries as well as large and medium-size elastic arteries
CML vs. leukemoid reaction
- both have increased WBC count
- differentiated based on neutrophil alkaline phosphatase level
- in leukemoid reaction (decreased alkaline phosphotase)
- in CML: decreased alkaline phosphatase
Causes of isolated systolic hypertension
- caused by age-related decrease in compliance (increased stiffness) of the aorta and its proximal major branches
Discuss protein C deficiency and Warfarin therapy
Transient pro-coagulant/anti-coagulant imbalance is present at start of warfarin therapy , leading to relative hypercoaguable state with thrombotic occlusion of microvasculature and skin necrosis
Sx: urinary urgency, nocturia, and hesistancy associated with constant back pain in elderly main
- Suggestive of metastatic prostate cancer
- Prostate cancer likes to metastasize to bone
Prostate cancer
- adenocarcinomas in PERIPHERAL zone of gland (vs. periurethral zone of gland in BPH)
- increased levels of PSA
- in advanced disease, may see elevated prostatic acid phosphatase (tumor penetrates capsule) and increase alkaline phosphatase
Discuss obstructive sleep apnea and EPO secretion
Obstructive sleep apnea - recurrent episodes of aphyxia during sleep
- peritubular cells in renal cortex sense hypoxia and release EPO which increases hematocrit
Cystic medial degeneration
- myxomatous changes in media of large arteries which development of aortic dissections and aortic aneurysms
Ovarian cancer
- presents as ovarian mass
- possible amenorrhea
- associated with CA-125
- risks of cancer decreased by OCP, multiparity, and breast feedings
Factors which decrease ovarian and/or endometrial cancers
** Things that decrease the number of ovulatory cycles
Multiparity
OCP use
Breastfeeding
Tx for hemorrhagic cystitis due to nitrogen mustard based chemotherapeutic agents
Mesna, a sulfhydryl compound that binds acrolein in urine
Tx of DVT in pregnant women
Heparin
- increases antithrombrin III activity
** Cant use Warfarin because it’s teratogenic
Clopidogrel
inhibits ADP mediated platelet aggeregation
used in treatment of coronary artery disease, peripheral vascular disease and cerebrovascular disease NOT DVT
Migratory thrombophlebitis
- should always think cancer
- hypercoagulability is very common paraneoplastic syndrome seen in adenocarcinomas of pancrease, colon or lug
- adenocarcinomas produce thromboplastin-like substance capable causing chronic intravascular coagulations
Nitroprusside
- agent of choice in treating hypertensive emergency
- quick onset of action and short duration of action
- initially metabolized to cyanide , with conversion to thocyonate by liver rhodanase
Treatment for nitroprusside toxicity
Na thiosulfate used to treat cyanide toxicity and works by donating sulfur to liver rhodamase to enhance conversion of cyanide to thiosulfate
Likely diagnosis:
necrotizing vasculitis of upper and lower respiratory tract (nasal ulcerations, sinusitis, hemoptysis) and rapidly progressive Wegners
- Wegner’s granulomatosis (granulomatous with polyangitis)
- cANCA
Tx for familial hyoalphalipoproteinemia
- low HDL thus increased risk of CAD
- Niacin (B3) is best treatment
Tx for hypercholesteremia
Statins and ezetimbe
- High LDL is a risk factor for atherogenesis
Ezetimbe
- tx of hypercholestermia
- decreases LDL by inhibiting cholesterol absorption from GI tract
- does not increase HDL concentrations
- used in combo with statins to achieve greater LDL reduction
Statins
- treatment of hypercholesteremias by inhibiting HMG CoA reductase, rate limiting enzyme of cholesterol syntehsis
- in response hepatocytes, INCREASE expression of LDL receptors
ApoB
apoprotein present in VLDL and LDL
- decreases in VLDL and LDL will cause apolipoprotein to decrease
Discuss energy expenditure in fatty acid oxidation vs. glycolysis in cardiac function
- More energy needed for fatty acid oxidation than glycolysis
- inhibition of fatty acid inhibitors promote oxygen effiency and decreases oxygen needed for cardiac support
Energy for sources of cardiac function
- Glycolysis
- Glucose oxidation
- Fatty acid synthesis
Main source of energy production in cardiac function
Fatty acid oxidation > Glucose oxidation > Glycolysis
Varicose veins
- caused by incompetent calves in lower extremities allow retrograde blood flow from deep to superficial veins
- increases pressure in superficial veins –> dilated veins
Orthostatic hypotension
- defined as fall > 20 mmHg in systolic pressure or >10 mm Hg in diastolic pressure
Describe events to correct normal physiological “orthostatic hypotension”
- Decreased venous return to heart
- Decreased ventricular filling and drop in CO and BP
- Drop in BP evokes compensatory baroreceptor reflect (increased sympathetic activity and decreased PS activity)
- Increased sympathetic tone raises peripheral vascular resistance via ALPHA-1 of peripheral vasculature. Leads to venous return and CO
Understimulaion of alpha adrenoreceptorss
- leads to cerebral hypoperfusion (light headedness and syncope
Sinus venosus
forms smooth portion of right atrium
Bulbus cordis
forms smooth portions of right and left ventricles
Primitive atrium
forms rough portions of left and right atrium
ductus arterious
derived from 6th embryonic aortic arch
Tertiary syphillis
- can result in thoracic aortic aneurysm
- compresses adjacent structures and dilates aortic valve ring, a murmur and mediastinal widening is heard
- aneurysm begins with vaso vasorum endarteritis and obliteration resulting in inflamation
FTA-ABS
specific test for syphillis
Gemfibrozil and fenofibrate (Fibric acid derivatives)
- first line treatments for hyperTRIglyceridemia
- decrease serum triglycerides by reducing hepatic triglyceride production
Bile acid resins (e.g. cholestyramine, colestpiol, colesevelam) and effect on triglycerides
- increase triglycerides
Niacin (Vitamin B3) used to treat…
hyperlipidemia
Side effects: cutaneous (flushing, warmth, itching) - better tolerated in slow release preparations
Capsaicin
- reduces pain by decreasing substance P in the peripeheral nervous system
Buerger’s disease
- seen in heavy cigarrete smokers < 35 years old
- associated with intradermal injection of tobacco extracts
- thrombosing vascultis extends into contiguous veins and nerves, encasing them in fibrous tissue
Polyarteritis Nodosa
- segmental, transmural, necrotizing inflammation of medium to small sized arteries in any organ
- typically affects kidney, liver, heart, and GI tract but NOT LUNGS!!
- sx: livedo reticularis, palpable purpura, hemorhage, ischemia
Cachexia
syndrome that encompasses anorexia, malaise, anemia, weight loss and generalized wasting due to underlying systemic disease.
TNF-alpha is a cytokine that causes necrosis of some tumors in utero
- Inhibitig
IVC
formed by union of right and left common illiac veins at level of L4-L5
- Renal arteries lie at L1
Apoptosis
can occur either the intrinsic (mitochondria-mediated) pathway or extrinsic (receptor-initiated) pathway.
- Both pathways require activation of caspases that cleave cellular proteins
Explain relationship between blood flow and resistance
Blood flow is directly proportional to vessel radius raised to fourth power.
Resistance to blood flow is inversely proportional to vessel radius raised to fourth power.
Foamy urine
- caused by proteinuria/ Heavy proteinuria (e.g. nephrotic syndrome) can caused interstitial edema because of decrease in serum albumn
Auer rods
deformed azurophilic granules found in cytoplasm of myeloblasts that stain positively for MYELOPEROXIDASE
- found in abundance in AML M3
Paroxysmal Nocturnal Hemoglobinuria
Triad: hemolytic anemia, hypercoaguable state, pancytopenia
- causes thrombosis
- deficiecy of CD55 and 59 which disallows complement activation
Hereditary spherocytosis
autosomal dominant condition that results form red blood cell cytoskeletaon abnormalities
- most commonly spectrin and ankrin defects
- definitive test: positive osmotic fragility test
Tx for hyperlipidemia
Niacin (Vitamin B3) - decreases synthesis of hepatic triglyceride and VLDL by suppressing release of FA from peripheral tissues
- also decreases VLDL conversion to LDL, thus decreasing LDL
- also increases HDL
Bile-acid binding resins
can cause constipation and abdominal bloating (potentiall worsening diverticulosis), hypertriglyceridemia, cholesteral gall stone and vitamin K malabsorption
Factor V Leiden mutation
causes factor Va resistance to inactivation by activated protein C, may account for approximately 20% of cases in atypcial venous thrombosis
Sx of hereditary spherocytosis
anemia, reticulocytosis and increased indirect bilirubin, indicating hemolytic anemia
- MCHC (increased because of mild dehydration of red blood cell)
- blood smear dysmorphic red cells with no central pallor
Henoch-Schonlein purpura
- seen in young boys (3 - 10 years old)
- palpable skin lesions associated with abdominal pain, arthralgias, and renal involvement
- occurs due to deposition of Ig-A containing immune complexes and shows up in purpura on buttocks, legs
Glioblastoma multiforme
- pallisading tumor cells around areas of necrosis
- commonly crosses midline (“butterfly distribution”)
- most common primary brain tumor in adults
AML (M3 variant)
- associated with Auer rods
- t(15;17) which codes for chimeric PML/RAR (retinoic acid receptor)
- this inhibits differentiation of myeloblasts and triggers development of APML
Selective COX-2 inhibitors
e. g. celecoxib
- have no effect on platelet aggregation and cause little GI irritation
- the reduced risks of GI bleeding are only advantages over traditional NSAIDS
Microangiopathic hemolytic anemia
- associaed with RBC fragments, Burr cells, and helmet cells
- in patients with prosthetic valves, RCs are exposed to excessive shear and turbulence in circulation causing damage
Glomangioma
- very tender small red-blue lesion under nail bed
- originates from modified smooth muscle cells that control thermoregulatory functions of dermal glomus bodies
Sx: “Mismatched V/Q with perfusion defect, sudden onset chest pain
Signs of pulmonary embolism
- often caused by deep vein thrombosis and continuum of pulmonary thromboembolism
Bile acid-binding resins (cholestyramine, colestpiol, colesevelam)
- bind to bile acid in GI tract, interfereing with its enterohepatic circulation
- LDL is decreased b/c hepatic cholesterol is consumed in re-sythesis of bile acids
- since bile is being re-synthesized, cholesterol content of bile increases thus increased risk of gallstone
Bcl-abl
- associated with CML
- result of t(9;22) - Philadelphia chromosome
C-myc overexpression
- associated with Burkitt’s lymphoma
- associated with t(8;14)
- myc oncogene on chr 8
- Ig heavy chain on chr 14
Li-Fraumeni syndromee
- autosomal dominant disorder caused by inherited mutation of p53
Bcl-2 overexpression
- associated with Follicular lymphoma
- associated with t(14;18)
- Bcl-2 has anti-apoptotic effects
Cyclin D1 overexpression
- associated with Mantle lymphoma
- associated with t(11;14)
Greater activity against Factor Xa and Thrombrin.
Unfractionated heparin or LMWH
Unfractionated heparin - contains pentasaccharide that binds to antithrombin causing confirmational change that increases ability to inactivate Factor Xa
- is able to bind to both antithrombrin and thrombrin to allow antithrombrin to inactivate thrombrin
Effect modification (of study)
- is present when effect of main exposure on outcome is modified by presence of another variable. Effect modificatiion is not a bias.
Atherosclerosis
initiated by repetitive ENDOTHELIAL cell injury, which leads to chronic inflammatory state in underlying intima of large elastic arteries as well as large and medium-size elastic arteries
CML vs. leukemoid reaction
- both have increased WBC count
- differentiated based on neutrophil alkaline phosphatase level
- in leukemoid reaction (decreased alkaline phosphotase)
- in CML: decreased alkaline phosphatase
Causes of isolated systolic hypertension
- caused by age-related decrease in compliance (increased stiffness) of the aorta and its proximal major branches
Discuss protein C deficiency and Warfarin therapy
Transient pro-coagulant/anti-coagulant imbalance is present at start of warfarin therapy , leading to relative hypercoaguable state with thrombotic occlusion of microvasculature and skin necrosis
Sx: urinary urgency, nocturia, and hesistancy associated with constant back pain in elderly main
- Suggestive of metastatic prostate cancer
- Prostate cancer likes to metastasize to bone
Prostate cancer
- adenocarcinomas in PERIPHERAL zone of gland (vs. periurethral zone of gland in BPH)
- increased levels of PSA
- in advanced disease, may see elevated prostatic acid phosphatase (tumor penetrates capsule) and increase alkaline phosphatase
Discuss obstructive sleep apnea and EPO secretion
Obstructive sleep apnea - recurrent episodes of aphyxia during sleep
- peritubular cells in renal cortex sense hypoxia and release EPO which increases hematocrit
Cystic medial degeneration
- myxomatous changes in media of large arteries which development of aortic dissections and aortic aneurysms
Ovarian cancer
- presents as ovarian mass
- possible amenorrhea
- associated with CA-125
- risks of cancer decreased by OCP, multiparity, and breast feedings
Factors which decrease ovarian and/or endometrial cancers
** Things that decrease the number of ovulatory cycles
Multiparity
OCP use
Breastfeeding
Sx of hemorrhagic cystitis
- can be result of nitrogen mustard based chemotherapeutic agent (e.g. cyclophosophamide or ifosfamide)
- metabolized by kidneys into ACROLEIN, which toxic to uroepithelial cells and cause renal cell death and necrosis
Tx for hemorrhagic cystitis due to nitrogen mustard based chemotherapeutic agents
Mesna, a sulfhydryl compound that binds acrolein in urine
Osler-Weber-Rendu syndrome
autosomal dominant condition marked by telangiectasias in skin as well as in mucous membranes of lips, oranonasopharynx, respiratory tract, GI, and urintary tract
- may cause epitaxis, GI bleeding or hematuria
Tx of DVT in pregnant women
Heparin
- increases antithrombrin III activity
** Cant use Warfarin because it’s teratogenic
Clopidogrel
inhibits ADP mediated platelet aggeregation
used in treatment of coronary artery disease, peripheral vascular disease and cerebrovascular disease NOT DVT
Tx for diabetic ketoacidosis
Intravenous hydration with normal saline and insulin
- This will result in serum glucose, osmolality, and potassium as increases in serum HCO3 and sodium
Phentolamine
Phenylephrine
- selective alpha adrenerigc agonist. Administation may be associated with reflect bradycardia
Isoproterenol
non-selective Beta adrenergic agonist that stimulates both B2 receptors vascular smooth muscle (vasodilation) and cardiac B1 (increases in cardiac rate and contractility)
Epinepherine (effect on systolic blood pressure, HR, and diastolic blood pressure)
Systolic BP: increases (alpha 1 and B 1) HR: increases (B1) Diastolic BP: (dose-dependent) Low dose - B2 > a1 (decrease) High dose - a1 > B2 (increase)
Propranolol
non-selective beta adrenergic antagonist
effect on B2: vasoconstriction
effect on B1: slows heart contractility
Fatty streaks
- multiple yellow spots approx 1mm in diam
- earliest lesion of atherosclerosis and present in all people > 10 y.o
- composed of lipid filled foamy cells and smooth muscle cells that have engulfed lipoproteins
- occurrence and location in child don’t predict locations of plaques later on in lide
Factor Xa inhibitors
- new class of anticoagulants with activity against factor Xa
- increase prothrombrin and aPTT times but don’t affect thrombrin time
Schilling test
- helps differentiate between dietary defiency of vitamin B12, pernicious anemia, and malabsorption syndromes
** Low absorpton of cobalamin not correctable by IF means malabsorptive syndrome such as ileal disease, pancreatic insufficiency, or bacterial overgrowth
Sx of steroid abuse
erythrocytosis
abnormal testicle size and function
hepatic abnormalities
acne
Strong evidence of lymph node malignancy
Monoclonal lymphocytic proliferation, esp. monoclonal T-cell receptor gene arrangements
Polyclonal proliferation of lymphocytes
associated with benign lymph node enlargement in response to antigenic stimulation
Sx of lead poisoning
- erythrocyte basophillic stippling
- microcytic anemia
Net filtration pressure
(Gh - Bh) - (Go - Bo)
von Willebrand disease
- causes impairments in platelet function and coagulation pathway abnormalities.
- associated with prolonged bleeding time
- prolonged PTT
- decreased platelet aggregation in response to ristocetin
Polycythemia vera
clonal myeloproliferative disease in pluripotent stem cells
- increased RBC mass, inc. plasma volume and low EPO
- majority have JAK2 V617F mutation, rendering RBCs more sensitive to growth factors
Strawberry hemangioma
benign vascular tumors of childhood
- appear during first few weeks of life, initially grow rapidly, then regress by 5-8 years old
- composed of capillaries separated by connective tissue
Alpha adrenergic agonists
- increase both systolic and diastolic blood pressure via stimulation of a-1 adrenoreceptors
- elevated systemic blood pressure is associated with reflex increase in vagal influence on heart, results in decreased heart rate
Vascular reaction to endothelial and intimal injury (e.g. atherosclerosis)
Intimal hyperplasia and fibrosis, predominantly mediated by reactive smooth muscle cells that migrate from media to the intima
Nitroprusside
- agent of choice in treating hypertensive emergency
- quick onset of action and short duration of action
- initially metabolized to cyanide , with conversion to thocyonate by liver rhodanase
Treatment for nitroprusside toxicity
Na thiosulfate used to treat cyanide toxicity and works by donating sulfur to liver rhodamase to enhance conversion of cyanide to thiosulfate
Likely diagnosis:
necrotizing vasculitis of upper and lower respiratory tract (nasal ulcerations, sinusitis, hemoptysis) and rapidly progressive Wegners
- Wegner’s granulomatosis (granulomatous with polyangitis)
- cANCA
Tx for familial hyoalphalipoproteinemia
- low HDL thus increased risk of CAD
- Niacin (B3) is best treatment
Tx for hypercholesteremia
Statins and ezetimbe
- High LDL is a risk factor for atherogenesis
Ezetimbe
- tx of hypercholestermia
- decreases LDL by inhibiting cholesterol absorption from GI tract
- does not increase HDL concentrations
- used in combo with statins to achieve greater LDL reduction
Statins
- treatment of hypercholesteremias by inhibiting HMG CoA reductase, rate limiting enzyme of cholesterol syntehsis
- in response hepatocytes, INCREASE expression of LDL receptors
ApoB
apoprotein present in VLDL and LDL
- decreases in VLDL and LDL will cause apolipoprotein to decrease
Discuss energy expenditure in fatty acid oxidation vs. glycolysis in cardiac function
- More energy needed for fatty acid oxidation than glycolysis
- inhibition of fatty acid inhibitors promote oxygen effiency and decreases oxygen needed for cardiac support
Energy for sources of cardiac function
- Glycolysis
- Glucose oxidation
- Fatty acid synthesis
Main source of energy production in cardiac function
Fatty acid oxidation > Glucose oxidation > Glycolysis
Varicose veins
- caused by incompetent calves in lower extremities allow retrograde blood flow from deep to superficial veins
- increases pressure in superficial veins –> dilated veins
Orthostatic hypotension
- defined as fall > 20 mmHg in systolic pressure or >10 mm Hg in diastolic pressure
Describe events to correct normal physiological “orthostatic hypotension”
- Decreased venous return to heart
- Decreased ventricular filling and drop in CO and BP
- Drop in BP evokes compensatory baroreceptor reflect (increased sympathetic activity and decreased PS activity)
- Increased sympathetic tone raises peripheral vascular resistance via ALPHA-1 of peripheral vasculature. Leads to venous return and CO
Understimulaion of alpha adrenoreceptorss
- leads to cerebral hypoperfusion (light headedness and syncope
Sinus venosus
forms smooth portion of right atrium
Bulbus cordis
forms smooth portions of right and left ventricles
Primitive atrium
forms rough portions of left and right atrium
ductus arterious
derived from 6th embryonic aortic arch
Tertiary syphillis
- can result in thoracic aortic aneurysm
- compresses adjacent structures and dilates aortic valve ring, a murmur and mediastinal widening is heard
- aneurysm begins with vaso vasorum endarteritis and obliteration resulting in inflamation
FTA-ABS
specific test for syphillis
Gemfibrozil and fenofibrate (Fibric acid derivatives)
- first line treatments for hyperTRIglyceridemia
- decrease serum triglycerides by reducing hepatic triglyceride production
Bile acid resins (e.g. cholestyramine, colestpiol, colesevelam) and effect on triglycerides
- increase triglycerides
Niacin (Vitamin B3) used to treat…
hyperlipidemia
Side effects: cutaneous (flushing, warmth, itching) - better tolerated in slow release preparations
Capsaicin
- reduces pain by decreasing substance P in the peripeheral nervous system
Buerger’s disease
- seen in heavy cigarrete smokers < 35 years old
- associated with intradermal injection of tobacco extracts
- thrombosing vascultis extends into contiguous veins and nerves, encasing them in fibrous tissue
Polyarteritis Nodosa
- segmental, transmural, necrotizing inflammation of medium to small sized arteries in any organ
- typically affects kidney, liver, heart, and GI tract but NOT LUNGS!!
- sx: livedo reticularis, palpable purpura, hemorhage, ischemia
6-mercaptopurine
- cytotoxic purine analog (along with 6-thioguanine) that inhibits de novo purine synthesis after being converted to active metabolites by hypoxanthine-gunine phosphoribosyl transferase (HGPRT)
- inactivated by XANTHINE OXIDASE in liver
Allopurinol
- inhibits xanthine oxidase and thus can increase 6-mercaptopurine significantly
Adenosine deaminase
- converts adenosine to iosine as part of purine metabolims
- enzyme is deficient in SCID
- inhibited by Pentostatin
Glioblastoma
- tumor from astrocytes and is common adult tumor
- typically found in hemispheres (frontal or temporal lobes) or near basal ganglia
- may become large enough to cross midline
- on gross exam: soft and poorly defined with areas of necrosis and hemorrhage
- poor prognosis
Meningiomas
- derived from arachnoid cells and 2nd most common tumor
- located on brain surface and attached to dura
- found on lateral and parasagittal brain convexities, falx cerebri, sphenoidal ridge and olfactory groove
Acoustic schwannomas
- special type that are arise from Schwann cells of CN VIII
- found at cerebellopontine angle
Precursor B-ALL immunophenotyping
can be distinguished from Precursor T-ALL by immunophenotyping
- TdT+
- CD10 +
- CD19+
Precursor T-ALL immunophenotyping
- express T-cell markers and are TdT+ CD2 CD3 CD4 CD7 CD8
Epstein-Barr Virus
- responsible for acute mononucleosis, nasopharyngeal carcinoma, lymphomas, and Burkitt’s lymphoma
- via contact through oropharyngeal secretions
- binds to CD21 on surface of B-cells and epithelial cells
Parvovirus
- attaches to human epithelioid cells via blood group P antigen (globoside)
- immature cells of erythroud family are most vulnerable and why fetal liver and adult bone marrow are most vulnerable
Essential to viral invasion of cells
the initial attachment of virion envelope or capsid surface to complementary cell surface receptorss
(e.g CD4 and HIV gp120) OR CD21 and EBVgp350
ERB-B2
- overexpressed in 25 - 30% of breast cancers
- member of epidermal growth factors
- transmembraine protein with tyrosine kinase activity and is present in breast/ovarian cells
- associated with aggressive cancers
Stop codons
UAG - “U Are Gone
UGA - “U Go Away”
UAA - “U Are Away
Treatment for cyanide poisoning
Amyl nitrates
- cause methoglobinemia which contains Fe (2+)
- Cyanide binds to Fe(2+)/ ferric iron more avidly than cytochrone enzymes which mitochrondrial enzymes
Anaphylatic shock
- characterized by vasodilation, increased vascular permeability, bronchoconstriction, hypotension, tachycardia
- epinephrine is treatment for anaphylatic shock
Aplastic anemia
- causes pancytopenia as bone marrow is replaced with fat cells and fibrous stroma
- absence of splenomegaly
- need bone marrow biopsy to distinguish from myeloproliferative disease
Polyarteritis Nodosa (PAN)
- TRANSMURAL inflammation with arterial wall fibrinoid necrosis
- sx;: fever, malaise, weight loss, abdominal pain and melensa
- associated with Hep B infection
Sx of norepinephrine extravasation
- blanching of a vein into which norepinepherine is being infused together with induration and pallor of tissues surrounding IV site
- due to leak of alpha-1 causing vasoconstriction
- prevented by administering phentolamine mesylate
Tx of norepinephrine extravasation
- alpha 1 blocker (phentolamine)
- counteracts the alpha-1 receptor mediated vasocontriction
Sx of aortic dissection
- severe retrosternal pain that radiates to pack
- intimal tear is thought to the initiating process
- intramural hematoma dissects through media and can compress major arterial branches
Vitamin K dependent coagulation factors
- II, VII, IX, X - (which are initially produced in liver until activation by Vitamin K
- failure of prolonged PT to correct with Vit K indicates liver disease
DIC (Disseminate Intravascular Coagulation
- associated with sepsis, particularly Gram - rods
- occurs to exposure of blood to procoagulants that initiate intravascular thrombosis, which is followed by thrombolysis
- result is consumption of coagulation factors, coagulopatjy, and bleeding
TTP-HUS
- TTP - associated with adults with neurological disorders
- HUS - associated with children with predominant renal involvement
- patients usually don’t bleed
- ONLY platelets are activated
- normal PT and PTT
- normal fibrinogen
DIC
- patients bleed
- coagulation cascade is activated
- PT and PTT are prolonged
- Low fibrinogen and increased FDP (fibrin degredation products)
Sx: Hemophilia
- history of hemarthrosis and bleeding after tooth extractions
- due to decreased levels of factors VIII (Hemophilia A) or levels of factors IX (Hemophilia B) which lead to failure to convert prothrombrin to thrombrin and deficient thrombrin formation
- Addition of thrombrin to hemophiliac patients’ serum causes clotting
Cliostazol
phosphodiesterase inhibitor used in patients with intermittent claudication
- inhibits platelet aggregation AND direct vasodilator
- shown to be superior to asprin in treatment of peripheral arterial disease
Ticlopidine / Clopidogrel
- similar drugs that block ADP receptor thus preventing GPIIb/IIIa receptors from functioning (platelet aggregation)
Argatroban
- anti-thrombic drug largely used in treatment of heparin induced thrombocytopenia
Concern when initiating ACE inhibitor therapy
- first dose HYPOtension
- risk factors: hyponatremia, hypovolemia secondary to diuretics, low baseline BP, high renin or aldosterone levels, renal impariemtn and heart failure
- minimize risk with low doses
Etoposide
chemotherapeutic agen that inhibits sealing activity of toperisomerase II.
- treatment causes chromosomal break to accumulate in dividing cells, causing cell death
Topoisomerases
- enzymes that relieve supercoiling that occurs during DNA replicating by creating nicks
Topoisomerase I – makes SINGLE stranded nicks
Topoisomerase II - makes DOUBLE stranded nicks
Most common VIRAL cause of aplastic crisis in patients with sickle cell anemia or chronic hemolytic anemia
Parvovirus B19 (non-enveloped, single stranded DNA virus) - infects erythroid progenitor cells
Hepatic C
- enveloped single stranded + RNA virus
Hepatitis E
NON-ENVELOPED single stranded + RNA virus
Paracortex of lymph node
populated by T lymphocytes and dendritic cells
- internal to cortex between follicles and medulla)
- can become enlarged during proliferation of T-lymphocytes
- poorly developed in DiGeorge Syndrome
Follicles of lymph node
sites of B cell lymphocyte localization and proliferation
- dense and dormant
- secondary follicles have pale germinal center containing proliferating B cells and follicular dendritic cells
-
Discuss agammaglobulinemia and follicles of lymph nodes
In agammaglobulinemia, germinal centers and primary lymph node follicle don’t form due to absence of B cells
Medulla of lymph node
- consists of medullary cords and sinuses
- medullary cords contain B cells, plasma cells, and macrophages
- medullary sinuses contain reticular cells and macrophages
Median
value that is located at the precise center of an ordered dataset. Divides the right half data from left side
BRCA-1 and BRCA-2
inherited as an autosomal dominant trait
BRCA-1 on chromosome 17 and is a tumor suppressor gene
- should be suspected if two or more relatives have premenopausal breast cancer
Hemolytic Uremic Syndrome
- affects young children and manifests with acute renal failure microangiopathic hemolytic anemia and thrombocytopenia
- decreased RBC count, hematocrine, platelet count
- Increased bleedigng time, LDH, BUN, and creatiine
Organisms associated with HUS
- E.coli O157:H7
- Shigella
Presence of erythroid precursors in liver and spleen..
- Extramedullary hematopoiesis, condition characterized by erythropoietin-stimulated hyperplastic marrow cell invasion of extramedullar organs
- caused by severed chronic hemolytic anemia, such as B-thalassemia
APC gene mutation
- found in patients with familial polyposis syndromes, sporadic colon cancer, and melenoma
- responsible for maintaining low levels of B-catenin (oncogenic) ad for intercellular adhesion
Non-nucleoside reverse transcriptase inhibitors
Nevirapine, Efavirenz, Delaviradine
Non-nucleoside reverse transcriptase inhibitors (Nevirapine, Efavirenz, Delaviradine)
- anti-retroviral drugs that do not require activation via intracellular phosphorylation
- best used with other anti-retroviral agents in treatment of HIV
Adverse effects of NNRTs (Nevirapine, Efiravenz, Delaviradine)
- abrupt onset of flu-like symptoms, jaudine, or fever - may indicate hepatic failure with encephalopathy
- most likely to occur during first 6 weeks of therapy
- Stevens - Johnsons syndrome
Pure red cell aplasia
Rare form of marrow failure characterized by severe hypoplasia of marrow erythroid elements in setting of normal granulopoiesis and thromboeisis
- involves inhibition of erythropoietic precursors and progenitors by IgG auto-antibodies or T lymphocytes
Pure red cell aplasia is associated with which conditions?
- Thymoma
- Lymphocytic leukemias
- Parovirus B19 infection
Volume of distribution
- hypothetical volume of fluid into which administered amt of drug would be need to uniformly distributed to produced observed plasma concentration
Volume of distribution formula
- amount of drug (mg)/ plasma concentration of drug (mg/L)
Low Vd (3-5L)
- high molecular weight
- high plasma protein binding
- high charge
- hydrophilicity tend to trap the drug
High Vd
- Lipophilic drugs tend to readily cross cell membranes and distribute widely outside the plasma and interstitial compartments
- tendency to collect with cells gives these drugs a high volume of distrubution
ARBs
- by blocking AT-1 receptors and inhibiting effects of angiotensin II
- results in arterial vasodilation and decreased aldosterone secretion
Discuss AT-1 receptors and RAAS
- Stimulation of AT-1 receptors on juxtaglomerular cells will decrease renin release from kidneys, consequently decreasing angiotensin I and II levels
Attributable risk percent
- measures of impact of a risk factor being studies
= (risk in exposed - risk in unexposed)/ risk in exposed
ARP = (RR - 1)/RR
Sickle cell patients are at increased risk for infection by which organisms
- Encaspsulated organisms (Strep pneumoniae and H. influenzae)
- Salmonells is most common cause of osteomyelitis, followed by E. coil and S. aureus
Reed Sternberg cells
bi-nucleated cells with “owl’s eyes” appearance that appear on background of lymphocytic infiltrate
- seen in non-Hodgkin lymphoma
Most common cancers in women
Incidence : Breast > Lung > Colon
Mortality: Lung > Breast > Colon
Rituximab
- monoclonal antibody directed against CD20 (B-cell marker) antigen.
- introduction of prognosis of some lymphomas
P450 microsomal oxidase system
- plays an important role in detoxification
- CCl(4) - produces free radicals that start vicious cycle of hepatic injury
Henoch Schonlein Purpura
- small vessel leukocytoclastic angiitis associated with IgA and C3 deposition
- most common in children in 3 - 11 years old
- most children with palpable skin lesions with or without abdominal pain and athralgias
Anti-retroviral agents
- selectively bind to HIV envelope transmembrane glycoprotein gp41 prevent the conformational changes necessary for viral membrane to fuse with target cellular membrane
- “fusion inhibitor”
Heparin
drug of choice for acute management of venous thrombosis or thromboembolism
- activates antithrombin III
Warfarin
inhibits Vitamin K dependent-carboxylation of glutamic acid residues of clotting factors II, VII, IX, and X (vitamin K dependent clotting factors)
Discuss ACE inhibitors and patients with bilateral renal stenosis
- May cause drop in GFR, as ACE inhibition leads to vasodilation of EFFERENT arterioles
Hyperplastic arteriosclerosis
- can result from perpetual malignant hypertension
- diastolic blood pressure > 120 - 130 mmHg
- leads to onion-like concentric thickening of walls of arterioles as result of laminated smooth muscle cells and reduplicated BM
- seen in renal vasculature
Hereditary spherocytosis
- results from RBC cytoskeleton abnormalities (deficient in ankyrin, spectrin)
Sx: hemolytic anemia, jaundice and splenomegaly
Aplastic anemia
- characterized by panocytopenia, low reticulocyte count, and absent splenomegaly
- usually “dry” and histopathology shows marrow replacement with fat cells and fibrous stroma
Myelofibrosis
- replacement of bone marrow with FIBROUS tissue (no fat)
- pancytopenia
- evidence of extramedullary hematopoiesis
Hairy leukemia
- can bone marrow fibrosis
- often described as “fried egg” appearance
- evidence of splenomegaly
Chloramphenicol
- lead to both dose-dependent (reversible) and dose-dependent (irreversible) pancytopenia
- anti-bacterial by binding to ribosomal 50 subunit and inhibiting peptidyl transferase enzyme thus suppresses bacterial synthesis
Gentamicin side efects
- Ototoxicity
- Nephrotoxicity
- Neuromusclar paralysis (
Metronidazole side effect
- Side effects are GI (nausea, vomiting, crampy abdominal pain)
- neurologica (parasthsias, dizziness)
- induces disulfiram-like reaction
Vancomycin-side effect
Can cause histamine release, results in flushing
“red man syndrome” - cause by rapid infusin
- dose-related ototoxicity
Common cardinal veins make what post-natal structure?
SVC
EBV virus
- causes infectious mononucleosis
- sx: sore throat, cervical lymphadenopathy, splenomegaly
- heterophile antibody tests sensitive
- associated with Burkitt lymphoma (African type) and nasopharyngeal carcinoma (in Cinese)
Features of anaplasia
- loss of cell polarity and normal tissue architecture
- variation in shape and size
- hyperchromatism and nuclear pleomorphisn
- High nucleus to cytoplasm ration
- Numerous, often abnormal mitoses
- giant, multi-nucleated tumor cells
Southwestern blotting
technique that analyzes DNA- binding proteins using pricincples of Southern and Western bots
- DNA- binding proteins recognized by ability to ind to specific oligonucleitides
Western blotting
- used to identify target polypeptide from saple
- target proteins undergo gel electrophoresis
- separated proteins are probed with specific antibody of interest
- then radioactive marker is bound to first antibody
Metalloproteinases
Zn-containing enzymes that degrade extracellular matrix.
- participate in tissue remodeling and in tumor invasion
Angioedema
- rare but serious effect of ACE inhibitors
- involves swelling of tongue, lips, or eye lipds and pts may experience difficulty breathing
- due to increased bradykinin levels
ACE inhibitors are contraindicated in which patients?
- In patients with peripheral vascular disease or atherosclerortic CV disease as they can develop ACUTE RENAL FAILURE
- patients with renal disease dependent on ACE constriction to maintain renal failure and ACE inhibitors would reduce renal perfusion
Causes of “LEFT” shift of oxygen - disassociation curve
- indicates increased oxygen- hemoglobin affinity (“L= LUNGS”)
- increased pH
- decreased CO2, temperature and 2,3 DPG
Causes of “RIGHT” shift of oxygen - disassociation curve
- indicates decreased oxygen-hemoglobin affinity
- decreased pH
- increased CO2, temperature and 2,3 DPG
Side effects of topic preparations of alpha-adrenergic agonists
- Alpha adrenergics can cause vasocontriction of nasal mucosa vessels and are used nasal decongestants
- Overuse can cause negative feedback resulting in decreassed NE synthesis
Streptokinase
- thrombolytic agents that acts by converting plaminogen to plasmin, which degrades fibrin
- most common side effect is hemorrhage
- foreign protein derived from Streptococci and can induce hypersensitivity reactions
Regulation of iron absorption
- regulated through hepcidin’s effect on absorption of dietary iron by intestinal epithelial cells and release of iron by macrophages
Discuss iron absorption
- After iron is absorbed by DMT-1, iron can take 1 of 2 pathways:
1. may bind to ferritin (intracellular iron-binding protein) and remain stored within enterocyte. can be excreted into stool as enterocytes are sloughed off
2. may enter circulation via ferroprotein, BL iron transporter of enterocyte. Free iron is transported by transferrin which becomes internalized after interacting with transferrin receptors on all cells
B-thalassemia
HbA2 is elevated in B-thalassemia minor (trait) and B-thalassemia intermedia because B-globin chain underproduction causes decreased synthesis of HbA
Hemoglobin components in adult blood
HbA1 = (a2B2) - 97% of total Hb HbA2 = (alpha2delta2) - 2.5% of total Hb HbF = (alpha2gamma2) - < 1% of total Hb
Hemophilia A
- defect in coagulation factor VIII
- NORMAL bleeding time (b/c bleeding is indication of platelet function)
- prolonged PTT
von Willebrand disease
- vWF is a mediator for coagulation factor VIII and mediator of platelet aggregation
- absence causes functional VIII deficiency and platelet deficiency
- prolonged bleeding time (platelet function)
- bleeding time
Warfarin inhibits which
- coagulants II, VII, IX, X
- anti-coagulants Protein C and Protein S
K-ras
- associated with cancers of bladder, lung, colon, pancreas and kidney
- proto-oncogene (tumor promotor) resulting stimulation of cellular proliferation, inactivation of anti-oncogenes
Proto-oncogenes
- ras: bladder/colon/pancreas/kidney
- ERB-B1: squamous cell of lung
- ERB-B2: breast/ovarian cancer
- TGFa: astrocytoma, hepatocellular carcinoma
- sis: astrocytomas, osteosarcoma
- abl: chronic myeloid leukemias
Anti-oncogene
- NFI
- APC/B-catenin
- DCC
- p53
- RB
- WT-1
Drugs that decrease progression of diabetic nephropathy
- ACE inhibitors
- ARBs
Age-related macular degeneration
- leading cause of blindness in industrialized nations
- involves degeneration of central retina
- “dry AMD” - subretinal deposits leading to gradual loss of vision
- “wet AMD” - more acute presentation - abnormal blood vessels with subretinal hemrrohage, gray subretinal membrane - due to increased VEGF
Tx of wet AMD
- due to increased vascular endothelial growth factors (VEGF) causing
- treat with anti-VEGF
Anti-inflammatory agents that do not inhibit platelet aggregation
Selective COX-2 inhibitors
**Platelets express mostly COX-1
Drugs that inhibit thymidylate formation
Methrotrexate
5-FU
** Note that methotrexate can overcome by N5-formyl tetrahydrofolate (folinic acid, leucovorin)
What metabolizes pro-carcinogens?
Hint: it’s in the liver
Converted by cytochrome p450 monooxygenase which is present in hepatocytes and ER of certain cells
- these enzymes convert the pro-oncogenes into active enzymes
Which organ extracts blood more efficiently than any other organ?
Heart - thus venous blood is the most deoxygenated.
HER2/neu oncogene
- encodes 185kd transmemembrane protein that has intracellular tyrosine kinase activity
- member of EGFR family
- overexpression can lead to breast and ovarian cancers
Statin side effect
Myopathy (leading to muscle pain)
- Statins commonly prescribed after MI as they reduce cholesterol and stabilize atheromatous plaques
Sx of T- ALL
- usually young child
- presents with mediastinal mass that can cause respiratory symtoms, dysphagia or superior vena cava syndrome
Aldosterone excess
- will canse hypertension, hypokalemia, metabolic alkalosis and depressed renin
Aldosterone antagonists (e.g. eplerenone and spironolactone)
- can cause hypoaldosterone (which can cause type IV renal tubular acidosis
- can be used as medical therapy for Conn’s syndrome (adrenal mass)
Aldosterone
- secreted by adrenal glands
Raltegavir
- integrase inhibitor that disrupts ability of HIV to integrate genome into the host’s cells chromosome, thus preventing host cellular machinery from being used to synthesize HIV mRNA
Patients with Sickle Cell Trait
HbA - 60%
HbS - 40%
** usually assymptomatic and have relative protection from malaria
- usually have normal peripheral smears and indices, reticulate counts and MCHC values
- may have RBCs that will sickle when sodium metabisulfite is added
Vinicristine side effect
- neurotoxicity (dose-limited) - results form failure of microtubule polymerization in neuronal axons
- pulmonary fibrosis and flagellate skin discoloration
Bleomycin side effect
Pulmonary fibrosis and flagellate skin discoloration
Doxorubicin side effect
CHF
Cycophosphamide side effect
hemorrhagic cystitis
Transketolase
- carry out non-oxidative reactions of HMP shunt
- some cells don’t use oxidative phase to produce cytosolic NADPH but ALL cells can syntehsize fructose-6-phosphate using the non-oxidative reactions
Giant cell arteritis
- characterized by granulomatous inflammation of media, with fragmentation of internal elastic lamina of medium and small branches of carotid artery
- most common in > 50 y.o paitent
- jaw claudication is most important symptom
- irreversible blindness due to ophthalmic artery occlusion is severe complication of GCA
- Tx: immediate prednisone therapy
Cherry hemangioma
- small red cutaneous papules common in aging adults
- don’t regress spontaneously and increase in number with age
- micro: proliferation of capillaries and postcapillary venules in the papillary dermis
Drug to prevent venous thrombosis in non-ambulatory patient or patients undergoing elective surgery
Heparin - increases the effect of naturally occuring anti-thrombrin III
Ancathocytes
“spur ce;;”
- seen in abetalipoproteinemia
Teardrop cells
- seen in myelofibrosis.
- when bone marrow is replaced with fibrosis (or metastatic cancer), RBCs must squeeze through spaces
Target cells
"bulls eye" cells - seen in "HALT" HbC Asplenia Liver disease Thalassemia
Schistocytes
- seen in DIC, TTP/HUS traumatic hemolysis (e.g. metal heart valve prosthesis)
DIC
- complication of gram - sepsis, acute pancreatitis, and burn injury
- gram negative spesis - activatio of coagulation cascade by bacterial endotoxins, causing formation of micro-emboli
Lab values for DIC
- fragmented RBCs (microangiopathic hemolytic anemia) and thrombocytopenia
- prolongation of PT, PTT, and decreased fibrinogen, factor V, and factor VIII levels
Most common cause of hypochromic, microcytic anemia
Iron deficiency
** most common cause of iron deficiency is blood loss
Suspected etiology of iron deficiency in woman of childbearing age
- Menstruation
Suspected etiology of iron deficiency of blood loss in adult male or postmenopausal woman
- Occult blood loss in GI tract
Common cause of thrombocytopenia
(esp. in patients with ecchymoses, petechiae, and mucosal bleeding with signs and symptoms of TTP/HUS, pancytopenia, marrow failure, and splenomegaly
Autoimmune destruction of platelets
ACE inhibitors on R-A-A- system
- INCREASED RENIN (due to decreased renal perfusion)
- INCREASED ANGIOTENSIN I, because renin converts angiotensinogen to angiotensin I
- DECREASED ANGIOTENSIN II because ACE inhibitors prevent this conversion
- DECREASED ALDOSTERONE because no angiotensin II to increase aldosterone secretion and induce vasoconstriction
- INCREASED BRADYKININ - because less angiotensin II means less degradation of bradykinin
-
Patient experiences parasthesias after receiving several units of blood. Serum calcium level is 7.2 mg/dL (hypocalcemic).
What’s the etiology?
- Patients who receive more than one body blood volume (5-6 L) over 24 hrs may have elevated citrate levels (substance added to blood)
- Citrate chelates calcium and magnesium and may reduce their plasma levels thus causing parasthesias
Discuss carbon monoxide poisoning and methemoglobinemia
- binds to hemoglobin with much higher affinity than oxygen, thus preventing oxygen from binding to hemoglobin
- DOES NOT AFFECT OXYGEN SATURATION
- DOES NOT CAUSE METHEMOGLOBINEMIA
Dysplasia
- REVERSIBLE change in epithelial cells
- progress through low-grade dysplasia –> high-grade dysplasia/carcinoma in site –> invasive carcinoma
- once breached basement membrane, no longer reversible
Amlopidine
- calcium channel blocker used to treat hypertension
side effect: flushing and peripheral edema
Discuss Hemoglobin S in deoxygenated state
- HbS aggregates in deoxygenated state
- ## form fibrous strands that reduce RBC membrane flexibility and promote sickling
Biphospoglycerate mutase
- produced in large quantities in erythrocytes
- creates 2,3 BPG from 1,3 BPG
Discuss 2,3 BPG and oxygen delivery to peripheral tissues
- 2,3 BPG is produced in erythrocytes with enzyme biphosphoglycerate mutae
- increased 2,3 BPG DECREASES affinity of Hb for oxygen thus allowing oxygen delivery to peripheral tissues