Goljan/Pathoma/UWorld Miscellaneous Flashcards
Caisson disease aka decompression sickness
atmospheric pressure increases –> N2 gas becomes dissolved in tissue
quick assent - bubbles emerge from solution, can occlude blood vessels
- quadriplegia - nerves of SC susceptible are highly susceptible
- loss of bladder control
- death
treat with hyperbaric oxygen chamber
anorexia nervosa
bulimia nervosa
anorexia nervosa:
distorted body image
refeeding syndrome - HYPOphosphatemia (P becomes trapped in intracellular space)
osteoporosis! - after you lose 15-20% body weight, GnRH release stops
- how do you treat this?
1) encourage weight gain - in general, for boards, think cheap
2) later consider birth control pills
death - due to heart failure
little evidence to support pharmacotherapy as primary treatment in anorexia
bulimia nervosa:
no distorted body image
vomiting - metabolic alkalosis with respiratory compensation
- hypoxemia - not good for heart –> premature ventricular contractions –> v. fib –> death
obesity
kg/(height m^2)
main complication is HTN (mechanism is not fully understood)
marasmus
kwashikor
marasmus:
- TOTAL calorie deprivation, nutrients still present
treat by feeding
- NO edema, there is muscle wasting
kwashikor:
missing protein = small child with swollen abdomen
-anemia
-cell immunity issues - cant fight against Candida, mumps
-low albumin, ascites, fatty livers (due to decreased apolipoprotein synthesis)
- skin lesions - hyperkeratosis and hyperpigmentation
-have to force feed - more likely to die (compared to marasmus)
there are two diseases where you want to restrict protein
- renal disease - protein means more urea
- cirrhosis of liver - defective urea cycle, cant metabolize ammonia
- most ammonia comes from bacteria - convert urea to ammonia –> ammonia is reabsorbed –> urea cycle in liver
- hepatic encephalopathy
vitamins ADEK
random note - water soluble vitamins are cofactors for biochemical reactions
- B complex def = dermatitis, glossitis, diarrhea
fat soluble vitamins - mineral oil intake can cause deficiency
A - growth (muscle, bone), rhodopsin, prevents squamous metaplasia (keratomalacia –> cornea goes soft –> blindness)
- essential for specialized epithelium - pancreatic tissue, goblet cells
- most common causes of blindness - trachoma (WW), DM (US), vitamin A deficiency
- follicular hyperkeratosis ~ goosebumps
- excess - hunter that eats bear liver –> cerebral edema, headache. Liver tox.
- acute tox - N&V, vertigo, blurred vision - teratogenic - cleft palate, cardiac abnormalities
………………………………………………………………………………
vitamin D - most importantly source is sunlight
-reabsorbed in jejunum
-PTH puts 1a-hydroxylase in the proximal tubule
increased bone mineralization at low levels, increased bone resorption at high levels
vitamin D binds to receptor on osteoBLAST- causes release of alk phos
-remember when calcitonin binds to osteoclast receptor - it inhibits the osteoclast, only hormone that binds to osteoclasts
PTH binds to osteoblast –> releases IL1 aka osteoclast-activating factor
- estrogen/testosterone keeps a check on IL1
- ….osteoporosis in women
deficiency - most commonly due to renal disease (DM is the most common cause of chronic renal disease in the US)
- all CRF pts are put on 1,25-vitamin D - NOT the formulation you get in the store
- over the counter vitamin D - has to pass through liver and kidneys
osteomalacia - soft bones, pathologic fractures
kids (rickets) - craniotabes (recoil when you press on the skull of a KID), rachitic rosary (because that is where osteoid IS, but it cant be mineralized)
- type 1 - missing 1a-hydroxylase
- type 2 (XD) - missing vitamin D receptor
…………………………………………………………………………………..
vit E- maintains cell membranes, prevents lipid peroxidation of cell membranes (prevents breakdown by phospholipase A)
- can also neutralize oxidized LDL - oxidized LDL is MORE atherogenic (LDL that macrophages phagocytose) = cardioprotective
deficiency is very uncommon - seen in kids with CF
- these kids have pancreas problems!!!
- can get hemolytic anemia - RBC membranes get damage
- myelin issues - posterior column disease, spinal/cerebellar-type disease
tox - prevents synthesis of vitamin K-dep coagulation factors = anti-coagulated
- can OD by taking an extra capsule
- OR if you are taking vitamin E with warfarin
……………………………………………………………………
vit K - phy-something
made by ANaerobes in the gut
-bacteria makes K2 - has to converted to the active form K1 by epoxide reductase
K1, gamma-carboxylase - glutamic acid residues carboxylated
- these coagulation factors are bound to a clot by Ca
- carboxylated glutamic acid residues BIND the Ca –> clot formation
scenario - rat poison = warfarin!, kid eats rat poison….
-treat with IM vitamin K
kid lives with elderly grandparents –> hemorrhage, why?
-kid ate grandparents warfarin
CYP 450 inducers
CYP450 system is in sER
inducers - phenytoin, alcohol, rifampin, barbiturates
- -> sER hyperplasia - items made in the liver are metabolized faster
- this includes drugs and 25-OH-vitamin D
scenarios
- pts can get hypocalcemia (vit D deficiency)
- lady on OCP + phenytoin - gets pregnant
GGT - enzyme of sER, that is why you have elevated GGT in alcoholics
vitamin C
hydroxylates proline and lysine - in the Golgi apparatus
deficiency - tea and toast diet
- hemarthrosis (and hemophilia A) - blood vessels are unstable and rupture
- perifollicular hemorrhages - ring (of blood) around the follicles
- glossitis
- hemorrhagic diaphysis
excess - GI upset, increase in uric acid stones, calcium oxalate stones, can increase Fe tox
- increases absorption of non-heme Fe - reduces Fe to Fe2+
vitamin C - ancillary treatment for methemoglobinemia, it is a scavenger for free radicals
cofactor for making catecholamines - makes NE from DOPA, epi from NE
thiamine B1
think ATP - lose the production of about 30 ATP (6 from pyruvate to acetyl coA, 24 from TCA)
pyruvate dehydrogenase, transketolase, a-ketoglutarate dehydrogenase (and branched-chain ketoacid dehydrogenase)
dry beri beri - need a lot of ATP to make myelin
- peripheral neuropathy (foot drop due to common peroneal palsy, wrist drop due to radial palsy, ulnar palsy), symmetrical muscle wasting
- W-K psychosis - Wernicke is confusion, ataxia, nystamus, ophthalmoplegia
- damage to medial dorsal nucleus of thalamus..
wet beri beri - (neuropathy +) heart failure
deficiency ddx by increased RBC transketolase following B1 administration
pt comes into ER comatose
give them
- IV glucose
- IV thiamine
- naloxone - in case of OD
niacin
nicotinic acid - lipid lowering agent that lowers VLDLs and increases HLD, used to treat familial combined HLD (elevated cholesterol and TGs)
- side effect flushing - take aspirin beforehand to avoid
deficiency can be caused by Hartnup dz (AR, tryptophan is a neutral amino acid), malignant carcinoid syndrome, izoniazid
pellagra, peripheral neuropathy
riboflavin B2
cofactor for glutathione reductase
deficiency - cheilosis, corneal vascularization, normocytic anemia
pyridoxine B6
converted to PLP (pyridoxal P) - ALT, AST, decarboxylation reactions, glycogen phosphorylase
synthesis of cystathionine, niacin, histamine, etc.
heme synthesis:
- succinyl coA + glycine, ALA synthase, B6 cofactor
- cytochrome system is also the heme system
cofactor for transaminase reaction
- alanine is the most important substrate for making glucose in the fasting state (alanine - NH2 –> pyruvate), a-ketoglutarate takes this NH2
- aspartate - NH2 –> oxaloacetate
(- glutamate -NH2 forms a-ketoglutarate)
synthesis of NTs
- neonates deficient in B6 will get seizures
most common cause of deficiency - isoniazid
def - peripheral neuropathy (isoniazid, OCPs)…
pantothenic acid
involved in fatty acid synthase - important in making palmitic acid and coA
def –> adrenal insufficiency
biotin B7
pyruvate carboxylase, biotin –> oxaloacetate
- pyruvate will build up and it will be forced to become lactic acid
cofactor for other carboxylation enzymes (acetyl –> malonyl, propionyl –> methylmalonyl)
deficient if you eat 7 raw eggs a day or with antibiotic use
- rash and go bald
trace elements
chromium:
glucose tolerance factor - helps insulin do its job
fl:
to prevent dental caries
too much Fl - white chalky teeth
- and calcification of ligaments where they insert into bone
selenium:
PPP and forming glutathione
- cofactor for glutathione peroxidase = selenium is an antioxidant (vitamin E capsules w/ selenium)
Cu
lysyl oxidase - cross links between collagen fibrils AND elastic tissue
dissecting aortic aneurysm
Zn
older person with dysgeusia = abnormal taste and anosmia = abnormal smell
rash on face and acrodermatitis enteropathica (desquamating rash on butt)
collagenase (metalloenzyme) contains Zn - breaks down type 3 collagen so you can make type 1 collagen
- poor wound healing
hypogonadism and decreased adult hair
diabetics are all Zn deficient
fiber
soluble fiber can lower cholesterol
insoluble fiber - hold water and toxins (lipocholic acid - carcinogenic bile acid) in the colon
- main method of recycling estrogen is through bile
- fiber will grab estrogen too - decreased risk of breast cancer
most common benign tumors
women: located in uterus - leiomyoma (aka fibroid), do NOT become leiomyosarcomas
men: lipoma
tubular adenoma
aka strawberry on a stick
precursor lesion to colon cancer
carcinoma
malignant cancer of epithelial cells
- squamous cells
- glands - adenocarcinoma
- urothelium - transitional cell carcinoma
melanoma
malignancy of melanocytes, nevus is the benign lesion
- S100 positive
- neural crest origin
step 1) excision
scenario- 2 yo with nodules to skin
- nodules are S100 positive
- answer - adrenoblastoma with mets to the skin
APUD tumor - a group of apparently unrelated cells
- neuroendocrine tumor
embryonal rhabdomyosarcoma
most common sarcoma of childhood
- grape-like mass off vagina or penis - desmin positive, striations on histology
mixed tumor
mixed tumors have 2 different tissues
parotid gland tumor - mobile mass at angle of the jaw
-usu malignant
v. s. teratoma - tumor of all 3 cell layers, germ-cell tumor
- 16 yo girl presents wiht RLQ pain, calcifications seen on imaging
- RLQ diff - ectopic pregnancy, appy, Crohns
- teratomas stay midline - pineal gland, ovary
leukemia
malignancy of stems cells in the bone marrow –> mets - LAD, HSM
lymphoma
these can metastasize
most common site for a lymphoma NOT developing in a LN - stomach
- aka extranodal primary lymphoma
- due to H. pylori
- second most common location - Peyers patches of terminal ileum
most common lymphoma - follicular B cell lymphoma
- knock off and apoptosis gene - 14,18 translocation
- B cell make BCl2 product - inactivates apoptosis gene
hydatidiform moles
pt presents with first trimester pre-eclampsia + edema
- US will show uterus too large for gestational age, snowstorm appearance
- benign tumor of chorionic villus
complete mole has greatest chance of evolving into choriocarcinoma - mets to lung
- but respond excellently to chemotherapy (methotrexate)
(??) maternal blood - synctiotrophoblast - cytotrophoblast - Wartin’s jelly - chorionic vein
synctiotrophoblasts makes hormones - bHCG and human placental lactogen (GH of pregnancy, aas and glucose from mom to baby)
hypoxia
inadequate oxygenation of tissue
ischemia - decrease in arterial blood flow
-most common cause is thrombus in muscular artery
hypoxemia - partial pressure of arterial O2 (O2 dissolved in blood ONLY)
- respiratory acidosis - increase in PCO2 means PO2 will go down
- shunt is where there is perfusion but not ventilation, giving O2 will NOT increase PO2
- perfusion defect - PE, increased dead space, giving O2 will increase PO2
- diffusion defect - fibrosis, sarcoidosis, pulmonary edema
cyanosis - decrease in O2 saturation
- metHb poisoning:
- scenario - man drinking water up in mtns, this water is loaded with nitrates/nitrites –> oxidize Hb. Giving O2 did not correct cyanosis.
- dapsone (used to treat leprosy), primaquine, TMP/SMX, nitro (nitroglycerin) and sulfa drugs - produce metHb, hemolytic anemia in G6PD deficiency. Because these drugs are oxidizing agents. HIV pts are on bactrim prophylaxis to prevent PCP.
- or due to NADH methemoglobin reductase deficiency
- treatment is IV methylene blue, ancillary treatment is vitamin C
- more on G6PD deficiency - oxidants cause sulfhydryl group cross-linking
cytochrome oxidase - last enzyme before e- is transferred to O2
- cyanide and CO inhibit cytochrome oxidase
- “three Cs”
…
J reflex
vagus nerve innervates J receptors/pulmonary C-fiber receptors - located in alveolar walls, close to pulmonary vessels
respond to pulm edema, PE, other cases where there is a decrease in oxygenation –> increase ventilation/respiration
= dyspnea
house fire
CO poisoning and cyanide poisoning (gas released when upholstery is burned)
first symptom of CO poisoning - headache!
CO poisoning
- PaO2 will be unchanged - because this is the amount of O2 dissolved in plasma
high altitude
PaO2 will be LOW - PiO2 is low - hypoxemia triggers hyperventilation
respiratory alkalosis - due to hyperventilation
renal compensation occurs by 24-48hrs
chronic changes
increased synthesis of 2,3-BPG
hemoconcentration - due to bicarb diuresis and fluid shift
increased pulmonary diffusing capacity
uncoupling of inner mitochondrial membrane
inner mitochondrial membrane is inappropriately permeable to H+
dinitrophenol (was used in dieting pills in the 1930s), alcohol, salicylates
hyperthermia
- in salicylate tox
- alcoholic on a hot day - good chance of getting heat stroke, mitochondria are uncoupled
respiratory acidosis
decrease in PO2 and O2 sat
tissue hypoxia
anaerobic glycosis –> lactic acid build up –> enzymes denature
- CANT apoptose because enzymes are denatured = coagulation necrosis (MI)
cellular swelling - reversible (when O2 is reintroduced)
- anything that is related to depleted ATP
irreversible change - Ca enters cells, because Ca-ATPase fails
- activates enzymes –> phospholipases damage cell membranes, nuclear pyknosis
(- remember hypercalcemia produces acute pancreatitis)
- also mitochondrial vacuolization - means that ATP production is permanently damaged
free radicals
settings: …phase 1 metabolism of drugs, carbon tetrachloride (drug, risk for centrilobular necrosis and fatty change of liver)
end product is lipofuscin - indigestable lipids
- will see this in the liver
- also called wear-and-tear pigment
reperfusion injury
when you give pure O2 to NRDS
R - retinopathy of prematurity due to free radical damage of retina
I
B - bronchopulmonary dysplasia - fibrosis in lungs
H2O –> OH due to radiation for cancer (ionizing radition)
- most common complication of radiation - leukemia
acetaminophen
tylenol
no 1 cause of drug-induced fulminant hepatitis - due to free radical production
damage occurs around central vein
free radicals also damage renal medulla and PGE2 knocked out - inability to concentrate urine
treat with N-acetyl-cysteine - replenish substrate for glutathione
methotrexate and leucovorin
methotrexate - competitively inhibits DHFR
leucovorin (folinic acid) given 24hrs after methotrexate - rescues normal cells, allows DNA to be made without folate
apoptosis
caspases
- lipofuscin cant be degraded
ex: councilman body - eosinophilic, dead cell in liver
extrinsic (how tumor cells are killed)
1) TNF binds to TNFR1
2) Fas ligand binds to cell surface receptor Fas
left heart emboli
vegetation from INFECTIVE endocarditis
mitral stenosis from group A strep -> clots in atria
dry gangrene
diabetic - atherosclerosis of popliteal artery
–> dry gangrene - means there is no pus
(small) bowel infarction
most common cause - bowel adhesions following surgery
2nd cause - entrapment in indirect inguinal hernia
–> hemorrhagic infarction
necrosis
coagulative: proteins denature, then enzymatic degradation
in granuloma
caseous: - mycobacterial infection or systemic fungal infection - lipid in cell wall of organisms other non-caseating granulomas - sarcoidosis, Crohns
liquefactive: neutrophils release lysosomal enzymes, then proteins denature
- infarction –> liquefactive necrosis in brain - B/C brain has no structural support (astrocytes but..)
- other cases of liquefactive necrosis - acute inflammation, neutrophils come in a damage tissue, abscesses
fat: acute pancreatitis, breast tissue
- damaged cells release lipase
fibrinoid - immune reactions, preeclampsia, mal HTN
gangrenous - distal extremity, GI tract
- dry - ischemic, cogulative
- wet - superinfection, liquefactive on coagulative
strep
hemolytic - lysins
DNase - degrades DNA in pus to facilitate the spread of the organism
releases hyaluronidase - breaks down GAGs in tissue
- allows infection to spread through tissues = cellulitis
gram positive diploccoci
- Strep pneumo - most common cause of bronchopneumonia
lung infarction
wedge shaped infarct - coagulative necrosis, hemorrhagic necrosis
- exudate, pleural effusion, neutrophils, blood –> pleuritic chest pain
pancreatitis
pain radiating to the BACK
SAD PUCKER
enzymatic fat necrosis
fibrinoid necrosis
necrosis of immunologic disease
palpable purpura - Type 3 HSR, small vessel disease
- alternative complement system - C5a - neutrophils do the damage
rheumatoid necrosis, vasculitis
malignant HTN, diabetes
liver
other sinusoid organs are - bone marrow, spleen
gaps between endothelium - RBCs, etc. can flow through these gaps
note: blocking HEPATIC vein will lead to liver congestion, blocking portal vein will do nothing
which part of liver is most susceptible to injury - around central vein (zone 3)
- zone 2 - yellow fever hits here
alcohol - increase in NADH and lactic acid production
- difficulty with gluconeogenesis - because of depleted pyruvate, fasting hypoglycemia
- ketoacids because of excess acetyl coA - will see b-hydroxybutryate in an alcoholic because it is an NADH-driven reaction
- fatty change in liver - glycolysis –> glycerol-3-phosphate –> VLDL (this is why restricting carbs reduces VLDL)
- and because of decreased FFA oxidation - due to increased NADH
- secondary issues - impaired lipoprotein assembly and secretion and increase in peripheral fat catabolism
hamartomas
bronchial hamartoma
- solitary coin lesion - lung
Peutz-Jeger syndrome
- hamartoma - no increased risk of neoplasm
hyperplastic polyp of colon
-most common type of polyp - hamartoma
malignant cells
longer cell cycle than original cell from which they were derived
upregulation fo telomerase
how many doubling times until you get a clinically detectable tumor - 30 doubling times
proteases, collagenases (to break through the basement membrane)
mets - lymphatic, hematogenous, seeding
- carcinomas - to LNs, specifically the subcapsular sinus
- exceptions - RCC/HCC go to vein, follicular carcinoma of thyroid goes to blood, choriocarcinoma
- sarcoma - hematogenous, go to lungs and bone
- seeding - surface ovarian cancers, glioblastoma and medulloblastoma in a kid seeds into spinal fluid
cancer in adults - we know (lung - non-small cell)
cancer in kids:
- incidence and death - leukemia, brain/CNS, neuroblastoma
death overall in US: heart disease, cancer
Pouch of Douglas
most dependent part in a lady
mets
usually mets are the most common cancer in org
- except - renal adenocarcinoma
- CT with multiple lesions = mets
Batson system - venous system, tributaries that connect deep pelvic and thoracic veins –> IVC –> vertebral bodies
- valveless system
- breast cancer can quickly spread to bone (vertebral column, head of femur)
1) lymph nodes are most commonly metastasized to
next most common) lung - mets from breast
next most common) liver - colon»_space; stomach > pancreas
- lung also mets to the adrenals
testicular cancer to peri-aortic lymph nodes - testes develop in abdomen and descend to pelvis
left supraclavicular node (Virchows node) - stomach
radionuclide scan - bone mets
- prostate, breast > lung, thyroid, kidney
- lytic mets (most mets) - multiple myeloma (why plasma cells have IL1 aka osteoclast activating factor)
- blastic mets - prostate cancer
- first step in checking for prostate cancer - DRE
- breast - mixed met
- axial skeleton
brain - mets from lung (why - lung is the most common killer) > breast > melanoma, colon, kidney
- at gray-white junction
desmin stains for muscle - muscle tumor
vascular malignancy - Weibel Palade bodies
steps of malignancy
1) initiation = mutation
- knocked out by point mutation - p53 (really all suppressor genes), Ras
- amplification (ErbB2)
- translocation - CML (Bcr-Abl fusion aka Philadelphia chromosome, 9:22)
- 8;14 - Burkitts lymphoma, C-myc (associated with EBV because it increases mitotic rate)
- when CD21 is bound, causes B cells to become plasma cells, receptor that EBV binds to)
- 14:18
- 15:17 - acute progranulocytic leukemia - treat with retinoic acid –> matures blast –> cancer becomes benign
Why? - chemicals (polycyclic hydrocarbons), viruses, radiation
2) promotion - multiple copies of mutation
3) progression - role of cancer cell, subspecializing what it will be resistant to
cis = proto-oncogene, makes growth factors
ErbB2 - codes for growth factor receptor
RET - MEN syndrome, receptor for growth factor
Ras - cell membrane messenger system (GTP)
Abl - cytosol, messenger system
- messages are sent to nucleus
nucleus:
N-Myc (neuroblastoma), C-myc (burkitts)
try to keep cell cycle in G1 phase: Rb suppressor gene p53 suppressor gene - DNA repair NF WT1 BRCA1 and BRCA2 - DNA repair genes
HCC
far east
factors: HBV, aflatoxin
HIV
associated with primary CNS lymphoma
most common cancer associated with radiation
leukemia - specifically CML (9;22)
papillary carcinoma of thyroid
basal cell carcinoma
non-ionizing radiation = UVB light = BAD
- thymidine dimers
(UVA is Wood lamp - used to find dermatophytes)
actinic keratosis aka solar keratosis - cancer that you can scrape off
- this is squamous dysplasia - arsenic predisposes
(- arsenic also involved in angiosarcoma of the liver, lung cancer)
- predisposes to squamous cell carcinoma
white eye reflex
most common reason - congenital cataract
TORCHES
- side note - congenital syphillis have tooth findings (Hutchinson’s incisors)
next - retinoblastoma
corticosteroids predispose to cataracts
skin cancers
AR - xeroderma pigmentosum - defect in DNA repair enzymes
upper lip up - basal cell
down - squamous cell
(other DNA repair enzymes - Wiskott-Aldrich, telangiectasias, etc.)
scar cancers in the lung
ex Tb scar –> adenocarinoma
otherwise chronic irritation, burns, draining sinus tracts –> squamous cell carcinoma
myasthenia gravis
NACh = ligand-gated sodium channel
- thymoma - question will show you a chest xray
- side note - hypogammaglobulinemia (Good syndrome) and pure red cell aplasia (anemia and low retics) assoc with thymoma
v.s. Lambert-Eaton myasthenic syndrome - occurs in small cell lung cancer
poliomyositis
symmetric proximal muscle weakness
- CD8 damage to skeletal muscle cells = autoimmune, increased CK
- endomysial inflammation - remember endomysium (muscle fiber) - perimysium (fasicle) - epimysium (fascia)
dermatomyositis
can see skin rash and inflammatory arthritis
postural muscles
soleus, paraspinal muscle - type 1 slow twitch
fibers (lots of myoglobin, mitochondria, aerobic respiration)
v.s. type 2a - ATP via aerobic metabolism
type 2b - glycogenolysis and glycolysis
osteoporosis
1) vertebral fracture - cancellous bone is affected first
2) cortical (compact) bone - hip fracture
PTH-independent hypercalcemia
humoral hypercalcemia of malignancy, vitamin D tox or excess Ca ingestion, thyrotoxicosis, immobilization
thyrotoxicosis - due to osteoclastic activity of thyroid hormones
host defenses
most important host defense system - CD8 T cells
- MHC1 –> CD8 cell releases perforin –> activate caspases
