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
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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
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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
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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
cachexia
caused by TNFa
irreversible - cant be fixed TPN
TNFa - acts on hypothalamus, suppresses appetite
- also increases BMR
pancreatic cancer
can also go to left supraclavicular node
Trousseau syndrome - recurrent migratory thrombosis of superficial veins (in chest wall, arms)
- because adenocarcinomas produce a thromboplastin-like substance
disseminated cancer - thrombocytosis (also occurs in myeloproliferative disease, Fe-deficiency)
fever in malignancy
most common cause is a gram negative infection
- E coli - indwelling catheter
- respirator - pseudomonas
- S. aureus (gram positive) - indwelling venous catheter
most common cause of death in cancer
paraneoplastic syndrome
most common is hypercalcemia - bone (IL1, PGE2 –> lytic lesions in bone), PTHrP (RCC, squamous cell carcinoma)
gastric adenocarcinoma
acanthosis nigricans
Leser-Trelat sign - seborrheic keratosis (esp ones that pop up overnight)
- black raised moles
hypertrophic osteoarthropathy
= clubbing + periostitis of long bones + arthritis
- inflammation of underlying bone –> results in proliferation of soft tissue = clubbing
associated with malignancy - primary lung cancer
can also see clubbing in bronchiectasis - clubbing is associated with hypoxemia
vegetations on heart valve
associated with mucous producing cancers - colon cancer
marantic endocarditis - vegetations are not infectious but they can embolize
- adenocarcinomas, esp pancreatic
need hx to separate from rheumatic fever
hyponatremia or Cushings
small cell lung cancer - APUD tumors, neural crest origin, S100 positive (nervous system specific cytoplasm protein, also present in melanoma cells)
- ADH, ACTH
renal adenocarcinoma
EPO and PTHrP
HCC
EPO and insulin-like factor –> secondary polycythemia and/or hypoglycemia
medullary carcinoma of thyroid
calcitonin is a tumor marker –> can be converted to amyloid
- can get hypocalcemia or Cushings
AD variant
male with testicular cancer
AFP - yolk sac tumor aka endodermal sinus tumor
- young kids
- AFP is also associated with HCC and open neural tube defects
- AFP is decreased in DS
b-HCG
multiple myeloma
Bence-Jones protein - light chain of immunoglobulin
- monoclonal spike (SPEP, M peak, M peak is also found in Waldenstrom macroglobulinema)
erythrocyte rouleaux formation on peripheral blood smear
tumor markers
Alk phos: bone, seminoma (placental ALP), exclude liver causes
ovarian: surface derived - CA-125
breast: CA15-3, 27-9
colon cancer:
carcinoembryonic antigen (CEA) - also in pancreatic cancer
- CEA-(anti-CEA) can deposit in kidney and produce diffuse membranous glomerulonephritis
most common tumor of brain in kids
pilocytic astrocytoma (cerebellum) - benign
most common cancer of brain - medulloblastoma (cerebellum)
most common childhood cancer
- leukemia - specifically ALL*
others: neuroblastomas (adrenal medulla), Burkitt’s lymphoma, Ewing sarcoma (onion-skin calcification), embryonal rhabdomyosarcoma
most common GYN cancer
most common - endometrial cancer
2) ovarian
3) cervical - PAP smear picks up cervical dysplasia
cancer killers
1) ovarian
2) cervical
3) endometrial - most common cancer has the best prognosis
only known tumor vaccine
HBV vaccine
galactosemia
AR - galactose-1P-uridyl transferase deficiency
neonatal jaundice and hepatomegaly, vomiting, cataract formation, failure to thrive, ID
- galactose-1P accumulation blocks phoshoglucomutase - cant convert G1P to G6P for entry into glycolysis
- can predispose to E coli sepsis in neonates
eliminate milk products from diet - use soy based formula
…..
galactokinase deficiency - AR, mild
- galactitol accumulates - galactosemia, galactosuria, infantile cataracts
- may present as failure to track objects or develop a social smile
galactitol is what causes cataracts in both
pale infarcts
heart, kidney, spleen
Trisomy 18
trisomies - error in meiosis nondisjunction (in oocyte)
micrognathia, prominent occiput, clenched hands with overlapping fingers, rocker bottom feet, hypertonia
hear defects (VSD, PDA), renal defects (horseshoe kidney), GI issues(Meckels, malrotation), limited hip abduction
prenatal US will show fetal growth restriction - majority die in utero
- 1/2 of live births die by 2 weeks
- surviving pts have ID
Cri-du-chat syndrome
5p deletion (p is the short arm) cat-like cry, hypotonia, failure to thrive, developmental delay
microcephaly, low-set ears, hyperterlorism (abnormally large distance between the eyes), broad nasal bridge
DiGeorge
22q11
aortic arch anomalies, thymic hypoplasia/aplasia and hypocalcemia
hypertelorism, low-set ears, micrognathia, cleft palate
HBV
proliferative phase
- HBV DNA and antigens present - antigens presented on MHC1
integrative phase - HBV DNA is incorporated into the host genome
- liver damage tapers off when antiviral antibodies appear and viral replication stops
- antibodies bind HbsAg - prevent binding of virus to hepatocytes - risk of HCC
there are immune complexes in HBV infection - cause early (arthralgias, urticaria) and chronic complications (GN, cryglobulinemia)
IgA
IgA antibodies bind to pili and other membrane proteins involved in adherence to bacterial mucosa –> inhibits mucosal adherence
Neisseria, S. pneumo, H. Flu have IgA protease
IgA is a weak activator of complement and a poor opsonin
H. flu - requires factor X (hematin) and factor V (NAD+) for growth
- unencapsulated strains are a cause of otitis media –> erythematous tympanic membrane
staph
staph protein A - binds Fc portion of IgG –> prevents complement fixation
all staph are catalase pos (distinguishes them from strep)
only s aureus is coagulase pos - can clot blood
- coagulase activates prothrombin –> fibrinogen is converted to fibrin –> organism is coated by fibrin and becomes resistant to phagocytosis
Tb
mycobacteria in general - Cord factor (serpentine cord, activates macrophages, and induces the release of TNFa)
- sulfatides (surface glycolipids) inhibit phagolysosome fusion
PPD negative in sarcoidosis or HIV infection
- primary tb - hilar nodes + ghon complex (usually mid/lower lobes)
HIV pts are at increased for tb regardless of CD4+ counts
isoniazid:
- inhibits mycolic acid synthesis
- mycolic acid holds carbolfuschin stain, resistant to decolorizer
- INH has to be processed by mycobacterial catalase peroxidase to be activated
- resistance can also occur if enzyme binding site is altered
- ADR: B6 deficiency, hepatoxic
ethambutol:
- inhibits synthesis of mycobacterial cell wall
- resistance when Mb increase production of arabinosyl transferase (enzyme that produces cell wall)
- optic neuropathy
pyrazinamide - has to be converted to active form by pyrazinamidase
- hepatotox, hyperuricemia
rifampin
- resistance - when there is mutation in the gene that codes for DNA-dep RNA polymerase
- rash, red-orange body fluids
(other mycobacteria - avium-intracellulare causes disseminated disease in AIDs, prophylax with azithro
- M scrofulaceum - cervical lympadenitis in kids
thoracic duct
drains lymph from left side of body and everything inferior to umbilicus
- empties into the left subclavian (where it junctions with the IJ)
bacterial toxins
Diphtheria toxin and P. aeruginosa exotoxin A - ribosylate and inactivate EF2
S. aureus
- enterotoxin - superantigen
- TSS - superantigen that stimulates T-cells –> widespread cytokine release and shock
C diff
- cytotoxin A - diarrhea
- cytotoxin B - induces actin depolymerization –> necrosis
Botulinum toxin - blocks pre-synaptic release of Ach at NMJ –> flaccid paralysis
Pertussis toxin
- ribosylates DISinhibits adenylate cyclase –> increased cAMP
- increased histamine sensitivity and phagocyte dysfunction
Cholera toxin - activates adenylate cyclase –> cAmP –> secretory diarrhea
C. perfringens - lecithinase aka phospholipase C aka a-toxin
- -> cell lysis (&hemolysis), vaso-oclusion, tissue necrosis, edema
- lecithinase also increases platelet aggregation and adherence molecule expression by leukocytes and endothelial cells
- C perfringens uses carbs for energy –> gas (so gas is not produced due to the toxin)
Strep pyogenes - streptokinase which converts plasminogen to plasmin
- erythema nodosum is most commonly associated with S. pyogenes (though it is a nonspecific finding)
intracellular pathogens
Legionella, N. gonorrhea, Listeria, viruses, Leishmania
injury and inflammation
injury –> neutrophils, macrophages –> TNFa, IL1, IL6 –> stimulate hepatic production of acute phase reactants
- many acute phase proteins bind to microbes –> fix complement
- fibrinogen (and IgG) - causes erythrocytes to from stacks that sediment fast than individual RBCs do = ESR
ESR - increased in anemias, renal disease, pregnancy, etc.
- decreased in sickle cell, polycythemia, HF, microcytosis, hypofibrinogenemia
side note - IgM cause RBCs to clump (normally RBCs have a negative charge to repel each other)
- cold agglutinins - can get Raynauds in cold weather
- cryoglobulins (these are not Ig) - proteins that agglutinate in the cold (remember HCV is highly associated with cryoglobulins)
acute inflammation (ex appendicitis) = absolute leukocytosis
- absolute increase in neutrophils with toxic granulation
- toxic granulation = O2-dep myeloperoxidase system - most potent system to kill bacteria - located in granules/lysosomes of neutrophils
- left shift - >10% band neutrophils
chronic inflammation - mononuclear cells and fibroblast mediated
bradykinin
vasodilation, increased vascular perm, mediates pain
smooth muscle CONTRACTion
PAF
=platelet activating factor
- vasoconstriction, bronchoconstriction, platelet stimulation
also enhances leukocyte adhesion to endothelium, chemotaxis, phagocytosis, and degranulation
drugs that affect warfarin
cyp450 inhibitors (increase warfarin effect)
- acetaminophen/NSAIDs
- antibiotics/antifungals (metronidazole, bactrim)
- amiodarone (watch out - pts with afib may be on amiodarone + warfarin)
- cimetidine, omeprazole
- cranberry juice, vitamin E, Ginkgo biloba
- thyroxine
- SSRIs
- the other problem with NSAIDs/ASA - they can also displace warfarin from its protein-binding site –> increasing the concentration of free warfarin
inducers
- carbamazepine, phenytoin
- Ginseng, St. John’s wort
- OCPs
- phenobarb
- rifampin
cholestyramine binds warfarin (and other drugs in the intestine)
warfarin particularly has an effect on factor 7 - prolongs PT and INR (INR is the ratio of PT/PTcontrol)
- for pts with afib, DVT, PE - want a INR of 2-3
Nocardiosis
gram positive rod (beaded, branching, looks like a thin hyphae)
- partially acid fast
- catalase positive
soil, healthy gingiva, inhaled, immunocompromised
pneumonia ~Tb, CNS involvment (ring-enhancing lesion aka abscess), cutaneous
treat with bactrim and surgical drainage of abscess
v. s. Toxoplasmosis (parasite!) - encephalitis and pneumonitis in HIV pts
- ddx with serology
- histopath will show cysts or zoites
Actinomyces
gram positive
cervicofacial (and abdominal) disease
- granulomatous inflammation + multiple abscesses
- sinus tracts that discharge sulfur granules
anti-emetics
used in motion sickness, hyperemesis gravidarum
anticholinergics - scopolamine
antiH - diphenhydramine, meclizine, promethazine
motion sickness - vestibular, visual, somatosensory systems integrate in vestibular nuclei
- M1 and H1 neurotransmission
chemo, visceral nausea (diabetic gastroparesis)
dopamine receptor antagonists - prochlorperazine, metoclopramide
- ADRs - diarrhea
serotonin antagonists - ondansetron
- headache, long QT, constipation
NK1 receptor antagonists - aprepitant, fosaprepitant
TB
caseating granulomas
- mycobacteria are phagocytosed by APCs –> CD4 cells are primed and release TNF and IFN-y –> stimulates macrophages and other leukocytes
activated macrophages secrete enzymes, ROS, etc. to destroy mycobacteria - collateral damage
Rim of T cells - around macrophages - caseous necrosis –> cavitary lesions
Tb produces cord factor (part of the cell wall) - prevents fusion with lysosomes
nucleotide excision repair
1) UV light –> thymidine dimers
2) endonucleases recognize deformed helix
3) ss cleavage and DNA repair (DNA poly, ligase)
xeroderma pigmentosum - AR
- photosensitivity, poikiloderma (associated with sun damage), hyperpigmentation in sunexposed areas
- deficient in endonuclease
Lynch syndrome (HNPCC) - DNA mismatch repair mutations - normally DNA polymerase has 3-5 exonuclease proofreading ability
Pseudomonas aeruginosa
malignant otitis externa in elderly diabetics - granulation tissue in ear pneumonia - CF, ventilated pts burn victims hot tub folliculitis ecthyma grangrenosum ~gangrene ulcer
MOTILE, aerobic gram-neg rod
OXidase positive
endotoxin (fever, shock), exotoxin (inactivates EF-2)
cipro, etc.
lungs and ribs anatomy
lungs end at rib 6
parietal pleura extends till rib 8
- thoracentesis - go between 6th and 8th rib (midclavicular line)
- insert between 10-12 if pts back is to you (paravertebral), between ribs 8-10 if pts side is to you (mid-axillary)
liver - can hit the liver if you insert the liver below rib 9, midaxillary line
intercostal vein, artery, and nerve lie on the LOWER border of the rib
urticaria
wheals - due to IgE-mediated degranulation of mast cells
- can also be due to non-IgE mechanisms/mast cell mechanism
- no IgE but mast cell degranulation - opiates, radiocontrast, physical urticaria
- no mast cells - ASA, hereditary angioneurotic edema
permeability of microvasculature –> edema in superficial DERMIS
- biopsy - mixed inflammatory infiltrate, engorged lymphatics
(deep dermal and subQ involvement = angioedema)
skin findings
acantholysis - loss of cohesion between keratinocytes
- pemphigus disorders
acanthosis - increased thickness of stratum spinosum
- psoriasis, seborrheic dermatitis, acanthosis nigricans
dyskeratosis - premature keratinization
- squamous cell carcinoma
spongiosis - intercellular EPIDERMAL edema
- spongiotic dermatitis - seen in eczematous dermatitis
vaccines
live attenuated - humoral and cell-mediated immunity
- MMR (rubella - PDA, sensorineural deafness, congenital cataract, generalized LAD and rash)
- rubella will was arthritis/arthralgia in the moms
killed - humoral only
- hepA, rabies
leukocyte IFN-a
inhibits various stages of viral RNA and DNA synthesis
- approved for HBV, HCV, hairy cell leukemia, condyloma acuminatum, Kaposi
lymphatic drainage
superficial lymphatics follow veins
deep lymphatics follow arteries
right lymphatic duct drains R body above diaphragm
mediastinal - trachea, esophagus
celiac - accessory abdomen and upper duodenum
SM - to splenic flexure
IM - to upper rectum
LE
- medial trunk (runs along saphenous) –> superficial inguinal nodes
- lateral track –> popliteal AND inguinal nodes
- popliteal - dorsolateral foot, post calf
superficial inguinal nodes - scrotum, perineum, ant abd wall, buttocks, skin of penis
- basically, cutaneous structures inferior to umbilicus and external genitalia below pectinate line
internal iliacs - prostate, bladder, vagina (middle third), cervix, lower rectum to anal canal above pectinate
para-aortic LN - testes, ovaries, kidneys, uterus
glans of penis and urethra - deep inguinals
external iliacs - deep lymphatics of abd wall + superficial nodes
Lyme disease
treat with doxy (aka tetracycline, first line), amoxicillin is first line in pregnancy
sulfonamide
use during the 3rd trimester - can displace bilirubin bound to serum albumin –> increased risk of neonatal kernicterus
Giardia
trophozoites = pathogenic, owl eyes cysts = infectious
if stool O&P is undiagnostic - small bowel biopsy will show villus atrophy
IgA and CD4+ are host defense mechanisms
- IgA deficiency, X-linked agammaglobulinemia, CVID have low IgA
v.s. Crypto and Toxo are intracellular intestinal pathogens
Roseala HHV6
less than 2 yo
3-5d of fever –> blanching maculopapular rash that starts on trunk and spreads to extremities
- can have febrile seizures
supportive care
v. s. Rubella and measles - rash that starts on the face and spreads to the trunk and extremities
- Rubella - spots on soft palate
- Measles - Koplik spots on buccal mucosa
- acute measles infection depletes vitamin A stores
seborrheic dermatitis
accumulation of scaly, greasy skin on face, ears, etc.
- seen in HIV and Parkinsons
ephedrine
related to methamphetamine
- treat asthma, decongestant, and stimulant effects
Chediak-Higashi
AR - granules in neutrophils and monocytes (immunodeficiency due to Staph, Strep), albinism, neuro defects (nystagmus, neuropathies)
- due defect in phagolysosome fusion –> granules = lysosomal inclusions
Wiskott-Aldrich
XL - immunodeficiency, eczema, thrombocytopenia
- combined B and T lymphocyte disorder
mTOR
growth factor receptor –> autophosphorylation of tyrosine residues –> PI3K –> AKT/PKB –> mTOR to nucleus –> cell survival (anti-apoptosis)
- endogenously inhibited by PTEN (PHOSPHATASE and tensin homolog)
upregulated in many cancer cells - rapamycin aka sirolimus = mTOR inhibitor
cytokine receptors
intracellular (rather than receptor) tyrosine kinases = JAK/STAT pathway
- STAT dimerizes and translocates to the nucleus
organic ACIDemia
thymidine, uracil
valine, isoleu, met, thre
cholesterol, odd-chain FAs
–> propionyl-coA + biotin –> methylmalonyl-coA –> succinyl coA -> TCA
propionic acidemia (AR) - propionyl-coA carboxylase deficiency
- severe metabolic acidosis - hypoglycemia and ketosis develop secondary to acidosis
- present as poor feeding, vomiting, hypotonic babies
- treat with low protein diet
lysine and leucine
ketogenic amino acids –> acetyl coA
DS and cancer
features: nuchal fold thickening, endocardial cushion defects, duodenal and jejunal atresia, hypotonia
10x-20x risk for ALL (and increased risk for AML)
Toxo gondii
intracellular PROTOZAn - cat is the host
- humans can get infected through contaminated water/meat (cysts)
cerebral toxo - encephalitis with ring-enhancing lesions (necrosis and seizures
- treat with pyrimethamine and sulfadiazine (can use clinda if sulfa allergy)
pt doesnt improve - probably CNS lymphoma
- non-Hodgkin B-cell lymphoma due to EBV
- EBV PCR of CSF, definitive ddx by brain biopsy
…………….
cryptococcal meningitis - amphoB
aspergillosis with CNS involvement (single ring-enhancing lesion) - + pulmonary and orbital manifestations
- use voriconazole
Listeria
gram positive bacteria that causes endotoxin-mediated septic shock (in general endotoxins are release during host immune activity or antibiotic treatment)
ampicillin
CMV
CMV - intracelluar inclusions
most common antibody in the US, most common blood tranfusion related infection
(most common cause of post-transfusion hepatitis = HCV)
retinitis, esophagitis, pneumonia, colitis, polyneuropathy, transverse myelitis, encephalitis
ganciclovir, use foscarnet if resistant to ganciclovir
- ganciclovir - guanine nucleoside analog, P- required
- foscarnet (IV) - pyrophosphate analog, doesnt required intracellular activation
- inhibits DNA poly (in herpes) and RT in HIV
metaplasia
squamous bronchial metaplasia: pseudostrat ciliated respiratory epi –> stratified squamous epi
Barret’s - esophageal squamous epi –> intestinal columnar epithelium
anticholinergics
…flushing
antihistamines (..doxylamine) TCADS (ami, imipramine) 1st gen antipsych esp low potency ones (chlorpromazine) clozapine benztropine, trihexyphenidyl atropine
prazosin
a1 BLOCKER - treat HTN and urinary retention (BPH)
anti-IL2
post-organ transplant to prevent graft v.s. host
granulation tissue
inflammatory cells
fibroblasts - fibroblast growth factor –> lots of blood vessels
keloid - excess of type 3 collagen deposition
- genetic predisposition - increased in black population
scenario: scar from 3rd degree burn and chronically draining sinus tracts (ex chronically draining osteomyelitis)–> squamous cell carcinoma
- lots of turn over in scar tissue - type 3 collagen replaced by type 1 collagen (requires Zn)
inflammation
acute
- neutrophils
- IgM (complement is heavily involved in acute inflammation)
- side note - IgG-activated complement only goes up to C3
- 10days -2 weeks - isotype switching (same plasma cell switches HEAVY chains) –> IgG becomes primary Ig
chronic
- lymphocytes
- IgG
granulomas - type 4 HSR (type 4 reactions are anything T cell mediated)
- alveolar macrophage phagocytoses Tb –> takes a tour of the body presents antigen to TH1 cells –> T cells release gamma-INF and macrophage inhibitory factor
- macrophage inhibitory factor keeps macrophage in that area = localized granulomas
- gamma-INF will activate macrophage (=epithelioid histiocyte) to kill organisms (Tb, systemic fungi) –> caseous necrosis
- when these macrophages die –> they form multinucleated giant cells
- macrophages secrete IL12 - activates TH1 T cells –> these T cells become the memory T cells
- Tb lives in calcified granulomas –> reactivates
- positive PPD - purified protein derivative injected into skin
- Langerhans cells (macrophages of skin, CD1, Birbeck granules) –> phagocytose protein derivated
- present to TH1 that has MEMORY of Tb exposure
- helper T cells releases cytokines –> inflammation, induration
- how about in elderly, AIDs - older people have less of an immune response (pts with AIDs will also not have a granuloma)
3rd degree burn
loss plasma and protein
celecoxib
COX1 - constitutively expressed, involved in housekeeping functions
COX2 - inducible, IL1 and TNFa cause COX2 upregulation
- COX2 metabolites increase pain sensitivity and inflammation
NSAIDS/ASA inhibit COX1 and COX2
celecoxib - selective COX2 inhibitor (minimize GI tox)
glucocorticoids decreased inflammation
bind to cytoplasmic receptors –> translocate to nucleus –> expression of anti-inflammatory peptides is upregulated (and COX2 transcription is downregulated)
minocycline
tetracycline
weak antirheumatic activity
side effects - photosensitivity dermatitis
ribavirin
used in HCV - INFa and ribavirin for pts with chronic infection (HCV RNA and liver inflammation/fibrosis)
1) phosphorylated intracellularly
- incorporated into RNA –> causes hypermutations –> lethal to RNA viruses
- directly inhibits HCV RNA polymerase
- inhibits IMP dehydrogenase - depletes GTP pools
- inhibits enzymes that form 5’-cap on viral mrNA
- enhances TH1-cell mediated immunity, inhibits TH2 cytokine production
side note - ribavirin also indicated for RSV
nerves through the skull
supraorbital fissure
- CN3, CN4, CN6
- nasociliary branch of CNV1
- ophthalmic vein
inferior orbital fissure
- CNV2
- infraorbital vessels
- sphenopalatine ganglion branches pass through the inferior orbital fissure
foramen rotundum
- CNV2
foramen lacerum occluded by cartilage
- internal carotid artery courses superior
foramen ovale
- CNV3
order of foramens
streptomycin
TB (sometimes), Yersinia pestis, tularemia
tabes dorsalis
20-30 years after primary infection
spirochetes cause damage to sensory nerves in dorsal roots –> secondary demyelination of dorsal columns
areflexia, loss of bladder function, positive Romberg
Argyll Robertson pupils - accomodate but dont constrict
- very difficult to dilate
- asymmetric
malaria
P. falciparum - trophozoites in RBCs (Giemsa stain)
- African species are chloroquine-resistant
- use mefloquine
P. v/o - add primaquine therapy
TDaP
first dose given at 2 mo - infant unable to mount a proper memory response earlier than this
biologics
- mab
- infliximab, certolizumab - anti-TNFa
- cept = receptor molecule
- nib = kinase inhibitor
- imatinib - CML and kit-positive GI stromal tumor
ribosomes
rER produces proteins for membranes and for export (including enzymes in ribosomes)
free ribosomes - produce cytosolic, mitochondrial, peroxisome matrix proteins
ribosome attaches to rER by translocon - binds 60S unit
calcification
dystrophic calcification - …liquefactive necrosis of chronic abscesses, schistosomiasis, congenital CMV, toxo, rubella, CREST syndrome
metastatic calcification
- predominantly in interstitial tissues of the kidney, lung, and gastric mucosa (these tissues lose Ca2+ quickly)
- nephrogenic DI and renal failure
PSaMMoma bodies = papillary carcinoma of thyroid, serous papillary carcinoma of cystadencarcinoma of ovary, meningioma, mal mesothelioma
exudate
due to lymphatic obstruction, inflammation/infection, malignancy
increased protein (>2.9g/dl) and LDH
Light criteria - determine if pleural effusion is exudative
cachexia
TNF, IFNy, IL1 and 6
P-glycoprotein
aka MDR1
classically in adrenocortical caricnoma (can be in colon and liver cancers)
cancers and risk factors
…
alcohol - SCC esophagus, HCC
aromatics (benzene, naphthylamine) - transitional cell bladder
ionizing rad - papillary thyroid carcinoma
alkylating agents - leukemia/lymphoma
EBV - … CNS lymphoma
HPV - …head and neck cancer
liver fluke (Clonorchis sinensis) - cholangiocarcinoma
S haematobium - squamous cell bladder carcinoma
amyloidosis
b-pleated sheets, congo red stain
AL (primary) - MM or plasma cells, affects and weakens multiple organ systems (even heme - easy bruising)
AA (secondary) - chronic inflam, multisystem
dialysis-related - b2-microglobulin, may present as carpal tunnel syndrome
heritable - transthyretin mutation
senile systemic - wild-type transthyretin deposited in ventricles (slower progression compared to AL)
- trans-thy-retin = carries T4 and retinol
organ-specific
- amylin in pancreatic islets
- ANP in atria - normal in aging, can predispose to a fib
- calcitonin in tumor cells of medullary thyroid carcinoma
apoptosis
ATP!
DNA-laddering - fragments of 180 bp
intrinsic - embryogenesis
- occurs when a regulating factor is withdrawn (ex decreased IL2) or in case of injury
- Bcl2 keeps outer mitochondrial membrane impermeable (overexpressed in 14;18 follicular lymphoma)
- DNA damage –> p53 activated –> Bax and Bak are proapoptotic
extrinsic
1) ligand-receptor - FasL binds to CD95 (thymic medullary selection) or TNFa binds to its receptor
2) CD8 releases perforin and granzyme B
paraneoplastic with lymphoma
increased vitamin D
other paraneoplastics
EPO: RCC/HCC, hemangioblastoma, pheo, leiomyoma
anti-NMDA encephalitis (general CNS disturbance) - ovarian teratoma
opsoclonus - myoclonus ataxia - neuroblastoma, small cell lung
antibodies against Purkinje cells –> cerebellar deg - small cell (anti-Hu), gyn and breast (anti-yo), Hodgkin (anti-Tr)
- anti-Hu in small cell can also cause encephalitis
bacteria -TLRs
normally NF-kb is bound to IKB
bacteria - TLR signals for phosphorylation and subsequent ubiquitination of IKB
NF-Kb –> synthesizes inflammatory proteins
TNFa increases neutrophil chemotaxis and macrophage phagocytosis
nosocomial infections
IV catheters:
staph
enterococci
candida
prophylactic antibiotics prior to surgery - cephalosporin covers normal skin flora
thrombosis in a vein - can occur due to a chronic indwelling catheter
arteries that run underneath the skull
middle meningeal artery - where frontal, temporal, parietal, and sphenoid bones join = pterion (thin)
middle meningeal is a branch of the maxillary artery facial a - courses over manidle
ext carotid –> occipital –> sternocleidomastoids…
ophthalmic - …forehead, hose
Kiesselbach’s plexus - site of nose bleeds
- sphenopalatine @ ophthalmic @ facial
patella and knee architecture
quads tendon wraps around patella –> patellar tendon
ACL - also prevents excessive tibial rotation
hams - hip extension, knee flexion
Candida
germ tubes are specific for Candida
- colonizes mouth, skin, vagina, intestine
superficial infections - with immunosupressed/HIV
disseminated infections in neutropenics - esophagus, heart, liver, kidney (spares lungs)
theophylline
methylxanthine - related to caffeine, used to treat asthma/COPD
causes mild cortical arousal and insomnia
- acute tox - GI upset, cardiac arrhythmias, and seizures
treat - give activated charcoal to decrease absorption, b-blockers to combat arrhythmia, and benzos for seizures
arboviruses
encephalitis
WNV - febrile viral illness, rash, encephalitis + flaccid paralysis
- pos ssRNA flavivirus - transmitted by mosquitos in the summer in the US
- supportive therapy
Togavirues (E, W, venezuelan equine encephalitis)
Bundayvirus (California encephalitis)
peptostreptococcus
ANaerobe
dental, cutaneous, intraabdominal infections
peroxisomal diseases
absence of peroxizomes
very long chain and branched chain FAs are NOT oxidized in the mitochondria - they are oxidized in peroxisomes
side note - mitochondria also does not metabolism fatty acids with branch points at odd-numbered carbons
ex Zellweger syndrome
- infants can form myelin properly –> seizures, hypotonia, mental retardation, early death
- hepatomegaly
Resfum disease - defect in peroxisomal alpha oxidation
- accumulation of phytanic acid and neuro disturbances
- treat by avoiding chlorophyll
penetrating injuries
front, T4, LSB - RV
- you can only hit the LV if you pass through the left lung
back, T8, right of vertebral bodies - IV
