P450 Stuff Flashcards
Substrates of P450
Anti epileptics
Theophylline
Warfarin
OCPs
Always think when outdoors.
P450 inducers
Chronic Alcohol Use St Johns Wort Phenytoin Phenobarbital Nevirapine Rifampin Griseofulvin Carbamazepine
Chronic alcoholics steal phen phen and never refuse greasy carbs
P450 Inhibitors
Sodium Valproate Isoniazid Cimetidine Ketoconazole Fluconazole Acute alcohol abuse Chloramphenicol Erythromycin Sulfonamides Ciprofloxacin Omeprazole Metronidazole
SICKFACES.COM
Red neurons with eosinophilia cytoplasm with pyknotic nuclei
24 hours post insult
Necrosis and neutrophils present in brain area
1-3 days post insult
Macrophages (microfilm) present in injured area
3-5 days
Reactive gliosis and vascular proliferation in injury area
1-2 weeks after injury
Glial scar
2 weeks
MUDPILES
Methanol Uremia Diabetic ketoacidosis Propylene glycol Iron Tables Lactic acidosis Ethylene glycol Salicylate
HARDASS
Hyperalimentation Addison RTA Diarrhea Acetazolamide Spironolactone Saline infusion
Calcium stones
Envelope shape
Calcium oxalate more common
Hypocitrateuria often associated with decreased urine pH
Calcium phosphate: increased pH, low sodium diet, thiazides
Ammonium magnesium phosphate crystals
Coffin lid
Increased pH
Urease positive bugs
Stag horn calculus
Uric acid crystals
Decreased pH
Lucent and not visible
Rhomboid or rosettes
Decreased volume, acidic pH
Cystine stones
Decreased pH
Invisible
Hexagonal
Cystine, ornithine, lysine, arginine malabsorption
RCC paraneoplastic syndromes
Chromosome 3 PEAR PTHrR EPO ACTH Renin
Poly cystic ovarian syndrome
Increased LH:FSH ratio Increased androgens from theca interna cells Decreased rate of follicular maturation leading to unruptured follicles and anovulation Enlarged bilateral cystic ovaries Hirsutisum and acne OHIO Oligomenorrhea Hirsutism Infertility Obesity
Centriacinar vs panacinar
Smoking is centriacinar
A1 antitrypsin is panacinar
Small cell carcinoma
ACTH Lambert Eaton antibodies SIADH Amplification of myc oncogenes common Cromogranin A and Enolase positive
PKU
Decreased phenylalanine hydroxylase or tetrahydrobiopterin
NEED TYROSINE
INtellectual disability, growth retardation, seizures, fair skin, eczema, musty body odor
Decrease Phenylalanine and increase tyrosine and supplement THB
MSUD
Blocked degradation of branched amino acids
Isoleucine, leucine, valine (I love Vermont maple syrup)
Decreased alpha ketoacid dehydrogenase
CNS defects, intellectual disability and death
Treatment: restriction of isoleucine, leucine, valine, thiamine supplementation
Alkaptonuria
HOmogentisate oxidase in the degradation pathway of tyrosine to fumarate
Blue black connective tissue, ear cartilage, sclerae, urine turns black on exposure to air
Homocystinuria defects and symptoms
Defects: Cystathionine synthase, decreased affinity of cystathionine synthase pyridoxal phosphate, methionine synthase deficiency
Symptoms: Increased homocysteine, osteoporosis, marfanoid habitus, ocular changes, cardiovascular effects, kyphosis, intellectual disability
OTC deficiency
Inability to initiate the urea cycle
Increased robotic acid in blood and urine, decreased BUN, symptoms of hyperammonemia
Lesch Nyhan syndrome
HGPRT - no IMP to GMP
Results in excess uric acid production
Intellectual disability, self multinational, aggression, hyperuricemia, gout, dystopia
Type 1 dyslipidemia
Lipoprotein lipase or C2
Pancreatitis, hepatosplenomegaly and eruptive/pruritic xanthomas
Type 2 dyslipidemia
Defective LDL receptor
Heterozygous have increased cholesterol but the defect is more pronounced in homozygotes
Relative risk
Risk of developing disease in exposed group vs unexposed group
Attributable risk
Difference in risk between exposed and unexposed (subtract)
Number needed to treat
1/absolute risk reduction
Number needed to harm
1/Attributable risk
Absolute risk reduction
Difference attributable to the intervention as compared to a control
Inspiration expiration effect on murmurs
RILE
Right inspiration
Left expiration
Atrial septal defect
Osteum segundum - most comment
Osteum primum - rare
Patent foramen ovale - missing tissue
Dopamine function
Prolactin decrease
TSH increase
cAMP hormones
FSH LH ACTH TSH CRH hCG ADH MSH PTH
cGMP
BNP
ANP
EDRF
IP3
GnRH Oxytocin ADH TRH Histamine Angiotensin II Gastrin
Intracellular receptor
Progesterone Estrogen Testosterone Cortisol Aldosterone T3/T3 Vit D
RTK
IGF FGF PDGF EGF Insulin
Nonreceptor tyrosine
Prolactin Immunomodulators GH GCSF Erythropoietin Thrombopoietin
MEN 1
Pituitary
Pancreatic endocrine
Parathyroid
Men2a
Medullary carcinoma
Pheochromocytoma
Parathyroid
Men2B
Medullary carcinoma
Pheochromocytoma
Mucosal neuromas
What is the pathway of the direct basal ganglia
Come straight into thalamus Cortex Striatum GPI Thalamus
Describe indirect basal ganglia pathway
Come straight, go externally, N get into thalamus Cortex Striatum GPE STN GPI Thalamus
What are the different types of primordial kidneys
Pronephros - early, degenerates
Mesonephros - Interim kidney for first trimester
Metanephric mesenchyme - goes to DCT
5 alpha reductive is responsible for
Penis and scrotum growth
Prostate formation
Testosterone forms
Seminal vehicle
Epididymis
Ejaculatory duct
Ductus deferents
Androgen insensitivty syndrome
Normal appearaning female
Female external genitalia with scant axillary and pubic hair, rudimentary vagina; uterus and Fallopian tubes absent
Increased testosterone, estrogen, and LH
Ataxia telangiectasia
ATM gene - failure to repair double stranded DNA breaks
Ataxia, spider angiomas, IgA deficiency
Cancer incidence in men
- Prostate
- Lung
- Colon rectum
Cancer mortality in men
1 Lung
2 Prostate
3 Colon/Rectum
Cancer incidence women
Breast
Lung
Colon
Cancer mortality women
Lung
Breast
Colon
Paradoxical splitting means…
Delay aortic valve closure (stenosis, left bundle branch block)
Fixed splitting
ASD
Wide splitting
Delay of RV emptying: Right bundle branch block or pulmonic stenosis
Kawasaki disease
Children under 4 CRASH and BURN Conjunctival injection Rash Adenopathyh Strawberry tongue Hand foot changes Fever
Polyarteritis nodosa
Middle aged men Hep B Fever and weight loss, malaise, headache GI: abdominal pain, melena Trans mural inflammation of the arterial wall with fibrinogen necrosis Microannurisms
Buerger disease
Heavy smokers, under 40 years old
Intermittent claudication
Ray aid phenomenon is often present
Wagner’s granulomatosis
Resp: Perforation of nasal septum, chronic sinusitis
Lower resp: hemoptysis, cough, dyspnea
Renal: Hematuria, red cell casts
Necrotizing vasculitis, granulomas in lung and upper airway
Microscopicc polyngitis
Necrotizing vassculitis commonly involving lungs, kidneys, skin with pauci-immune glomerulonephritis and palpable purport
Eosinophilia granulomatosis with polyangitis
Asthma, sinusitis; skin nodules or purpura, peripheral neuropathy
Heart GI or kidneys
Enoch schonlein purpura
Skin: Palpable purpura
Arthralgias
GI: abdominal pain
Follicular cyst
Unruptured follicle that is associated with hyperestrogenism, endometrial hyperplasia
PDH complex cofactors
The lovely coenzyme for nerds Thiamine pyrophosphate Lipoid acid CoA FAD NAD
Type 2 dyslipidemia
LDL receptors defective
Accelerated atherosclorsis, xanthomas, corneal arcus
Dysbetalipoproteinemia
ApoE defective
Premature atherosclerosis, tuberoeruptive xanthomas,, xanthomas striatum palmare
Type 4 dyslipidemias
Hepatic overproduction of VLDL
Hypertriglyceridemia can cause acute pancreatitis
What causes the lyric lesions seen in multiple myeloma
Neoplastic plasma cells activate RANK receptor on osteoclasts leading to bone destruction
What is the effect of dopamine secreted from the kidney
Natriuresis
Low doses dilate interlobular arteries, afferent arterioles and efferent arterioles
What is acute respiratory distress syndrome caused by?
Sepsis, infection shock, trauma, aspiration, pancreatitis, DIC, hypersensitivity reactions, and drugs
Cholesterol stones
Opaque
Obesity, Crohns, advanced age, estrogen, multi parity, rapid weight loss, NA origin
Pigment stones
Black and radiopaque
Crohn disease, chronic hemolysis, alcoholic cirrhosis, advanced age, biliary infections, total parenteral nutrition
TTP mechanism
Inhibition or deficiency of ADAMTS13 (vWF metalloprotease) and decreased degradation of vWF multimers
Neurological, renal symptoms, fever, thrombocytopenia, microangiopathic hemolytic anemia
Contents of cavernous sinus
CNIII, IV, V1, VI and occasionally V2 postganglionic sympathetic pupillary fibers en route to orbit all pass through cavernous sinus.
Porphyria cutanea tarda
Uroporphyrinogen decarboxylase deficiency
Uroporphyrin tea colored urine
Cutaneous photosensitivity and hyperpigmentation
Most common porphyria
Amyloidosis kidney findings
LM - Congo red stain shows apple green bifringence under polarized light
Kidney is commonly involved in systemic amyloidosis
Diabetic glomerulonephropathy findings
LM: Mesangial expansion, GMP thickening, eosinophilia modular glomerulosclerosis
Nonenzymatic glycosylation of GBM means increased permeability
Increased GFR
What is minimal change disease findings
LM - normal glomeruli, IF -, EM, effacement in foot process
Most common cause of nephrotic syndrome in children. Triggered by recent infection, immunization, immune stimulus
FSGS
LM - segmental sclerosis and hyalinosis
IF - negative but may be positive for nonspecific focal deposits of IgM, C3, C1
EM - effacement of foot processes similar to minimal change
Membranous nephropathy
LM - diffuse thickening of capillary and GBM
IF - granular as a result of immune complex deposition
EM - spike and dome appearance
Acute poststreptococcal glomerulonephritis
LM - glomeruli enlarged and hypercellular
IF - granular appearance due to IgG, IgM, and C3 deposition along GBM and mesangium
EM - subepithelial immune complex humps
Most frequently seen in children after group A strep infection
Rapidly crescentic glomerulonephritis
Crescent moon shape consisting of fibrin and plasma proteins with glomerular parietal cells, monocytes, and macrophages
Goodpasture syndrome, wegner’s, microscopic polyangitis
Diffuse proliferation glomerulonephritis
Often due to SLE or membranoproliferative glomerulonephritis
LM - wire looping
EM - subendothelial and sometimes intramembranous IgG based ICs often with C3 deposition
IF - granular
IgA nephropathy
LM - mesangial proliferation
EM - mesangial IC deposits
IF - IgA based IC deposits in mesangium
Renal pathology of Henoch-Schonlein purpura
What is Alpert syndrome
Mutation in type 4 collage meaning thinning and splitting of glomerular basement membrane
X dominant
Membranoproliferative glomerulonephritis type 1
Type 1 - subendothelial immune complex deposits with granular IF, tram track appearance on PAS stain and H&E stain due to GBM splitting caused by mesangial I growth
Secondary to hep B and C infection
Membranoproliferative glomerulonephritis type 2
Dense deposit disease
Associated with C3 nephrotic factor and persistent compliment activation and decreased C3 levels
B5
Pentothenic acid, CoA
Dematitis enteritis, slope is, adrenal insufficiency
B6
Converted to pyridoxal phosphate, a cofactors used in transamination, decarboxylation reactions, glycogen phosphorylase, synthesis of cystationine, heme, niacin, histamine, neurotransmitters including serotonin, epinephrine, norepinephrine, dopamine, GABA
What is the effect of TRH on prolactin
Increased
Bruton’s agammaglobulinemia
BTK gene defect leading to no B cell maturation
Recurrent bacterial and enteroviral infections after 6 months
Absent B cells in peripheral blood and decreased immunoglobulins
Selective IgA deficiency
Mostly Asymptomatic Airway and GI infections Autoimmune disease Atopy Anaphylaxis to IgA containing products IgA decreased with normal Ig everywhere else
Common variable immunodeficiency
Defect in B cell differentiation
Increased risk of autoimmune disease, bronchiectasis, lymphoma, sinopulmonary infections
Decreased plasma cells and decreased Ig
What is IL12 receptor deficiency?
Decreased Th1 response
Isseminated mycobacterial and fungal infections; may present after administration of BCG vaccine
Decreased IFN-gamma
Autosomal dominant hyper IgE (Jobs)
Th17 deficiency due to stat3 mutation impaired recruitment of neutrophils to sites of infection
FATED
Fancies, cold staphylococcal Abscesses, retained primary Teeth, Increased IgE, Dermatological problems
Increased IgE, decreased IFN gamma, increased eosinophils
Chronic mucocutaneous candidiasis
T cell dysfunction
Noninvasive Candida infection of skin and mucous membranes
Absent in vitro T cell proliferation in response to candida
SCID
IL2 gamma chain defect, adenosine delaminates deficiency
Failure to thrive, diarrhea, thrush, recurrent infections
Decreased T cell receptor excision circles
Absence of thymic shadow, germinal centers, and T cells
Hyper IgM syndrome
Defect in CD40L on Th cells leading to decreased class switching Hyper IgM but decreased Ig of any other types Failure to make germinal centers
Wiskott Aldrich syndrome
WASp gene mutation; leukocytes and platelets unable to recognize actin cytoskeleton leading to defective antigen presentation
WATER: Wiskott Aldrich, thrombocytopenia, eczema, recurrent infections
Increased Risk of autoimmune disease and malignancy
Decreased IgG and IgM
Increased IgE and IgA
Cheddar Higashi syndrome
Defect in lysosomal trafficking regulator gene
Microtubule dysfunction in phagosome-lysosomes fusion; AR
Recurrent progenitor infections by staph and strep, partial albinism, peripheral neuropathy, progressive neurodegeneration, infiltration lymphohistiocytosis
What is the cause of the lumpy bumpy appearance of poststreptococcal glomerulonephritis
Deposition of IgG, IgM and C3 along the GBM and mesangium
What is the cause of diffuse proliferative glomerulonephritis
Subendothelial and sometimes intramembranous IgG based ICs often with C3 deposition
What is the appearance of IgA nephropathy?
Mesangial proliferation
Mesangial IC deposits
IgA based immune complex deposits in mesangium
Focal segmental glomerulosclerosis leads to deposition of what?
Can be positive for IgM, C3, C1
What is stress incontinence
Outlet incompetence leading to leaking with increased intaabdominal pressure, increased risk with obesity, vaginal delivery, prostate surgery
Tx: Pelvic floor muscle strengthening, weight loss, pessaries
What is urgency incontinence?
Overactive detrussor leading to leaking with urge to void immediately
Treat with antimuscarinics
What is mixed incontinence?
Features of both stress and urgency incontinence
What is overflow incontinence?
Incomplete emptying with leak with overfilling
Increased post void residual on catheterization on ultrasound
What are the causes of acute pancreatitis?
I GET SMASHED Idiopathic Gallstones Ethanol Trauma Steroids Mumps Autoimmune disease Scorpion sting Hypercalcemia/hyperlipidemia ERCP Drugus
What is the difference between central and nephrogenic DI?
Central - pituitary tumor, autoimmune trauma, surgery, ischemic encephalopathy, idiopathic
Nephrogenic - Hereditary, secondary to hypercalcemia, hypokalemia, lithium, demeclocycline
Central has decreased ADH
What is SIADH?
Ectopic ADH
CNS disorders
Pulmonary disease
Drugs
Where is coagulative necrosis seen?
Ischemia and infarct in most tissues
Where is liquefaction necrosis seen?
Bacterial abscesses and brain infarcts
Where is caseous necrosis seen?
TB, systemic fungi, nocardia
Where is fibrinoid necrosis seen?
Preeclampsia, immune reactions in vessels, malignant hypertension
What is seen in Tay Sachs?
Hexosaminidase A deficiency leading to GM2 buildup
Neurodegeneration, developmental delay, red macula spot, onion skin lysosomes
What occurs in fabry’s disease?
Early: Episodic peripheral neuropathy, angiokeratomas, hypohidrosis
Late: Progressive renal failure, cardiovascular disease
Alpha galactosidase A deficiency leading to ceramide trihexoside
What is metachromatic leukodystrophy
Central and peripheral demyelination, with ataxia and dementia
Arylsulfatase A deficiency leading to cerebrospinal sulfate
What is seen in Krabbe disease?
Peripheral neuropathy, destruction of oligodendrocytes, developmental delay, optic atrophy, globoid cells
Galactocereprosidase deficiency leading to increased galactocerebroside
Gaucher disease
Hepatosplenomegaly, pancytopenia, osteoporosis, a vascular necrosis of femur, bone crises, Gaucher cells(tissue paper cells)
Glucocerebrosidase deficiency leading to increased glucocerebroside
Niemann Pick disease features
Progressive neurodegeneration, hepatosplenomegaly, foam cells, and cherry red spot on macula
Defect in sphingomyelinase leading to increased sphingomyelin
What are the features of intravascular and extravascular hemolysis?
Intrinsic: decreased haptoglobin, schistocytes on blood smear, characteristic hemoglobinuria, hemosiderinuria, urobilinogen in urine. May also see increased unconjugated bilirubin
Extrinsic: Macrophages in spleen clear RBCs. Spherocytes in peripheral smear, no hemoglobinuria/hemosiderinuria