DIT

Tremor, sedation, edema
hear block
hypothyroidism
polyuria (ADH antagonist causing nephrogenic diabetes insipidus)
teratogenesis

Almost exclusively excreted by kidneys -- most is reabsorbed at the proximal convoluted tubules following Na reabsorption

is a medical condition combining clubbing and periostitis of the long bones of the upper and lower extremities. Distal expansion of the long bones as well as painful, swollen joints and synovial villous proliferation are often seen. The condition may be primary or secondary to diseases like lung cancer.

most commonly due to bronchogenic adenocarcinoma

1. upper limb, lateral breast
AXILLARY

2. stomach
CELIAC

3. duodenum, jejunum
SUPERIOR MESENTERIC

4. sigmoid colon
COLIC --> INFERIOR MESENTERIC

5. rectum
INTERNAL ILIAC

6. anal canal
SUPERFICIAL INGUINAL

7. testes
SUPERFICIAL AND DEEP PLEXUS --> PARA-AORTIC

8. scrotum
SUPERFICIAL INGUINAL

9. thigh (superifcial)
SUPERFICIAL INGUINAL

10. lateral side of dorsum of foot
POPLITEAL

A-a > 30 means there is something wrong with the lung

1. Ventilation defect (impaired I2 delivery to alveoli for gas exchange) -- RDS

2. Perfusion defect (decreased or absent blood flow to alveoli) -- PE

3. Diffusion defect (O2 cannot diffuse through alveolar capillary interface) -- interstitial fibrosis, pulmonary edema

4. R-->L shunts -- tetralogy

Yersinia enterocolitica

Cold growth, outbreaks of diarrhea often in daycare centers

1. high altitude, hypoventilation, respiratory acidosis

2. depression of respiratory center in medulla (e.g. barbituates, brain injury)

3. upper airway obstruction (eppiglottis due to H. influenzae, croup due to parainfluenza)

4. chest bellows dysfunction

Leptospirosis includes flulike sympyomes, fever, headache, ab pain, jaundice, photophobita with conjunctivitis.

Wil's disease -- severe from with jaundice and azotemia from liver and kidney dysfunctionl fever, hemorrahe, and anemia

aortic valve closes before pulmonic; inspiration increases this difference by leading to drop in intrathoracic pressure, which increases circulation. Pulmonic valve closes later to accommodate more blood enterind lung; aortic valve closes earlier b/c of decreased return to the heart.

1. Redness -- active hyperemia & congestion; bleeding & solid (red hepatization)

2. blood broken down --> grey (grey hepatization)

3. resolution (healing)

pneumococcus most common, then klebsiella

sulfadiazine + pyrimethamine

Seen in conditions that delay RV emptying (pulmonic stenosis, right bundle branch block).

Delay in RV emptying causes delayed pulmonic sound (regarless of breath) -- an exaggeration of normal splitting

metronidazole and iodoquinol

seen in ASD. ASD leads to L --R shunt and increased flow through pulmonic valves such that regardless of breath, pulmonic closure is greatly delayed.

Fibrosis = scarring and adhesion
Abscess, which can rupture, leading to empyema (pus with inflamatory cells) spreading to the rest of the lung, which if enters the blood stream can lead to septic shock

Seen in conditions that elay LV emptying (aortic stenosis, left bundle branch block). Normal order of valve closure is reversed so that P2 sound occurs before delayed A sound; therefore on inspiration, the later P2 and earlier A2 sounds move closer to one another "paradoxically" eliminating the split.

Localized collection of pus within parenchyma, usually resulting from bronchial obstruction (cancer) or aspiration of oropharyngeal contents. Often due to s. aures or anerobes

Causes --
Septic emboli
preexisting pneumonia
obstruction to bronchi

Complications --
could destroy an artery, leading to hemoptysis
Amyloidosis in long term inflammation
empyema

Intersitial -- inflammation in septa NOT alveolus! No evidence of consolidation

See thickening in septae with inflammatory cells

M. pneumonia
Chlamydia pneumoniae
Adeno, Influenze, RSV

intensity increased with inspiration

fever and hemolytic anemia; predom in NE US (maltese cross)

guinine, clindamycin

intensity increased with expiration

Staphylococcus aureus

caseated nodules w/pink center granulomas
mutlinucleated giant cells
acid fast red rods

First 2 months -- INH, rifmapin, pymzinamide
Next 4 months -- INH + rif; if resistant, ethbutamol, streptomycin

undercooked meat, usually pork; inflammation of the muscle, periorbital edema, myocarditis.

loudest at apex and radiates toward axilla

enhanced by maneuvers that increase TPR (e.g. squatting, hand grip) or LA return (e.g. expiration).

MR is often due to ischemic heart disease, mitral valve prolapse, or LV dilation. + rheumatic fever

TB bacilli will invade bloodstream, get into lymphatics (Gohn complex)

intestinal infection, vomitting, diarrhea, anemia, a/w HTLV-1

treat with bendazoles or pyrantel pamoate

loudest at tricuspid area and radiates to right sternal border

Enhanced by maneuvers that increase RA return (e.g. inspiration).

TR is due to RV dilation or endocarditis. + rheumatic fever

granulomas spread throughout lung -- milliary spread (small) and cavitations

>15 mm in low risk
>10 mm in high risk (IV drug, poverty, immigrant)
> 5 mm in HIV, recent TB

Brain -- Meninges
Neck -- Cervical lymph nodes, laryngeal chords
Liver
Spleen (also miliary spread)
Lower lumbar spine (Pod's disease)
Fallopian tubes
Epidydymis

acute stress -- 2 months and 1 month

PTSD -- longer than a month

food contaminated with eggs; causes granulomas (if in retina --? blindness) and visceral larva migrans

Stimulates 5=HT receptor

does not cause sedation, addiction, or tolerance.

Takes a week to work

depression, but

1. venlafaxine is also used in generalized anxiety disorder

2. duloxentine also indicated for diabetic peripheral neuropathy

Tanea solium (cysticercosis)
Diphyllobothrium latum (from fish, B12 def)
Echinocossus (eggs in dog feces can cause cysts in liver, causes anaphylazis if echinococcal antigens are released from cysts -- surgeons inject ethanol before removal to kill daughter cysts)

general -- (nonspecific) for at least 6 months

adjustment -- (specific) for < 6 months; < 6 months in presence of chronic stressor

problem getting air out of the lung because of increased resistance to air flow

FEV1/FVC decreased
TLV, RC, RV elevated because can't get the air out

hypertensive crisis with tyramine inghestion (in many foods, esp aged foods) and b-agonists

tyramine stimulates NE release; MAO inhbited will lead to no degradation

schistosoma
clonorchis sinesis
paragonimus westermani (undercooked crab meat; causes inflammation and 2ndary bacterial infection of lung, causing hemoptysis)

treat with praziquantel

problem getting air in, can't expand

TLC, VC decreased because of decreased lung volume
FEV1/FVC is either normal or increased

blocks NE reuptake

atypical antidepression -- sedation, orthostatic hypotension

a2-antagonist (increases releease NE and serotonin) and potent 5-HT receptor antagonist

tox: sedation, increased appetitde, weight gain, dry mouth

Asthma
Chronic bronchitis
Emphysema
Bronchiectasis

primarily inhib serotonin reuptake

used for insomnia -- increases REM sleep, as high doses are needed for antidepressant effects

tox: sedation, nausea, pripism, postrual hypotension

acute stress -- 2 months and 1 month

PTSD -- longer than a month

Pox

Chest Wall -- obesity, kyphoscholiosis, polio

Interstitial -- ARDs, pneumoconiosis, pulmonary fibrosis, sarcoidosis, Goodpasture's, Wegener's, drug toxicity

Nocardia asteroides

Stimulates 5=HT receptor

does not cause sedation, addiction, or tolerance.

Takes a week to work

Cough, sputum for 3 months over past 2 years; hypoxia, weight gain b/c CHF, dypsnea, frequent infection

Hypertrophy of mucous glands (increased wall gland ratio-->Reid index=gland depth/thickness of wall. In COPD> 50%) in the bronchioles

squamous cell metaplasia, which can lead to infections, hypoxia (vasoconstriction --> cor pulmonale, hypertension)
SCC

sarcoidosis
amyloidosis
postradiation fibrosis
endocardial fibroelastosis (thicl fibroelastic tissue in endocardium of young children)

Loffler's syndrome (endomyocardial fibrosis with a prominent eosinophilic infiltrate)
and hematochromatosis

destruction of alveolar septa. enlargment of air spaces and decreased recoil resulting from destruction of alveolar walls, increased compliance

similar to other depressants (anxiety, tremor, seizures, insomnia)

severe -- delerium tremens (treat with benzos)

Reo

Boys 4-12 months
1. Recurrent bacterial infections

2. Pyogenic bacteria S. pneumoniae, H. influenzae and strep

3. Chronic infections

4. Septic and non-infectious arthritis

5. Meningitis

6. Enteroviral infection

7. PCP infection

8. XLA and cancer

1. centrilobular/acinar -- due to smoking. enlarged airspaces, especially in apex.
respiratory brochioles are destroyed with distal alveoli spared

2. panacinar/lobular -- entire lung destroyed due to a1-antitrypsin deficiency
respiratory bronchioles and distal alveoli

3. Paraseptal -- associated with bullae, which can rupture, leading to spontaneous pneumothorax; often in young, healthy males

activate locus ceruleus (NE) pathway and NAC

CNS depression, nausea & vomiting, constipation, pupillary contriction, seizures

Calci
Picorna
Reo

Pap
Adeno
Parvo

1. Major abnormality is lack of B lymphocyctes in peripheral blood and other organs (<2% CD19+)

2. Absence of immunoglobulin production

3. Rudimentary lymph tissue with abnormal histology

4. Absent plasma cells

5. Bone marrow shows arrest of B cell maturation

90 - 95% of patients with XLA have a BTK mutation

1. extrinsic -- type I hypersensitivity (pollen, dust, food, etc), usually starts in childhood

2. Intrinsic (unknown mech) -- viral, stress, exercise in cold, aspirin triggers

test with methacholine challenge.

Findings: cough, wheezing, dyspnea, tachypnea, hypoxemia, decreased I/E ratio, pulsus paradoxus, mucus plugging

Abscess formation
Cor pulmonale
Amyloidosis
Aspergillosis

1. Increased H (LHF)
2. Decreased oncotic pressure (liver disease -- not enough albumin)
3. Capillary destruction (bleomycin, heroin, shock, radiation, infections to lung)

Rota

upper lobe cavitation
thick mucous & fat gram negative rods
association with an alcoholic

Ras

Peripheral
Pleura
Puckering
Forms glandular spaces, tends to produce mucous

1. Bonchial
2. Bonchoalveolar (more rare)

1. Bronchial -- develops in site of prior pulmonary inflammation or injury (most common lung cancer in nonsmokers and females)

2. Bonchioalveolar -- not linked to smoking; grows along airways; can present like pneumonia; can result in hypertrophic osteoarthropathy

Keratin pearls
Intercellular bridges (desmosomes)

undifferentiated--> very aggresive, often associated with paraneoplastic syndromes:

ACTH (Cushing's)
ADH (SIADH)
Eaton-Lambert (autoantibodies against Ca channels, leading to large muscle weakness in the morning)
Acanthrosis Nigricans

complication of isoniazid
produces pyridoxine defeciency
B6 is necessary in heme synthesis in the mitochondria of RBCs
leads to a sideroblastic anemia

Phage-mediated transfer of host-DNA.

transmitted by Aedes mosquito

high fever, black vomit, hemorragic disease, and jaundice

Peripheral
Highly anaplastic undifferentiated tumor
Less responsive to chemotherapy
Poor prognosis

Plepmorphic giant cells with leukocute fragments in cytoplasm

H. influenza
Adeno
S. pnuemoniae

secretes erotonin, can cause carcinoid syndrome (flushing, diarrhea, wheezing, salixation). Fubeous deposits in right heart valves may lead to tricuspid insufficiency, pulmonary steonsis, RHF

In G-, DNA is transferred via conjugative plasmid (F pilus) to recipient cell by physical contact.

In G+ cell, plasmids are transferred not through a pilus but through contact b/w two cells, induced by quorom-sensing.

R factor is a plasmid that contains drug resistance gene.

Rhino
Corona
Adeno
Influenza C
Cox

1. parasite in host; long, slender form
2. in bloodstream; short, stumpy form
3. taken up by tsete fly; forms procyclic form which multiplies in gut
4. grows into eptmastigote form in fly's saliva
5. epimastigote --> metacyclic form
6. new bite will infect animal

Parasite also has a VSg on its surface, leading to evolution of parasite so that it can propogate again in genetically modified vectors.

Associated with foundries, sandblasting, and mines. Macrophages respond to silica and release fibrogenic factors, leading to fibrosis. May disrupt phagplysosomes and impair macrophages, increasing susceptibility to TB.

Affects upper lobes, ground-glass appearance, nodular opacities, "eggshell" calcification of hilar lymph nodes insidious onset

All contain surface F (fusion) protein, which causes respiratory epithelial cells to fuse and form multinucleated cells.

Palivizumab is used in RSV to neutralize F protein

Salmonella typhi

Associated with shipbuilding, roofing, and plumbing. Results in "ivory white" calcified pleural plaques. Assocated with an increased incidence of bronchogenis carcinoma and mesothelioma.

Affects lower lobes. Golden beaded appearance in sputum

Increased risk (as with smoking) for primary lung cancer, THEN mesothelioma

Neisseria (pili)
Strep (M protein)
Mycoplasma
Lyme

SPHERE

Superior VC syndrome -- distended head and neck veins, plethora, facial, and upper arm edema
Pancoast's
Horner's
Endocrine (paraneoplastic)
Recurrent laryngeal symptoms
Effusions (pleural or pericardial)

Autonomic ganglia
NMJ

T. brucei (afircan sleeping sickness)
Plasmodium falciparum

Decreased protein content. Due to CHF, nephrotic syndrome, hepatic cirrhosis

First dose orthostatic hypertension

Shigella
Salmonella
Listeria

Increased protein content, cloudy
Due to malignancy, pneumonia, collagen vascular disease, trauma (occurs in sates of increased vascular permeability). Must be drained in light of risk of infection

CN toxicity

Influenza
HIV (env)
Flavi (E protein)

nitroprusside
fenoldopam
diazoxide

CMV retinitis and esophagitis
disseminated M avium-intracellulare
cryptococcal meningioencephalitis

increased cGMP, direct release NO

Isoproterenol -- relaxes bronchial SM (b1); adverse affect is tachycardia (b2)

Etoposide
Bleomycin
Cisplatin

dopamine D1 receptor antagonist, relax renal SM

Albuterol (relaxes bonchial SM) -- use during acute exacerbation


Salmeterol (long acting agent for prophylaxis)

Dactinomycin
Vincristine

L --> r shunts
mitral regurg, prolapse, post MI, CHF, etc

HMG-CoA reductase inhibitors

hepatotoxicity

Any drugs that prolong the QT interval:

macrolides
sotalol
quinidine
risperidone
halliperidol
protease inhib
chloroquine
methadone

It is a methylxanthine that likely causes bronchodilation by inhibiting phosphodiesterase, thereby decreasing cAMP hydrolysis.

Usage limited b/c of narrow therapeutic index (cardiotoxicity, neurotoxicity); metabolized by P-450. Blocks actions of adenosine.

Inhibits lipolysis in adipose tissue; reduces hepatic secretion into circulation

red, flushed face, which decrease by aspirin or long-term use
hyperglycemia, hyperuricemia

Ipratopium -- competitive block of muscarinic receptors, preventing bronchoconstriction. Also used for COPD

CD 14

Prevent intestinal reabsorption of bile acids; liver must use cholesterol to make more

cholestyramine
colestipol
colesevlam

GI discomfort
decreased ADEK
cholesterol gallstones

Prevents release of mediators from mast cells. Effective only for the prophylaxis of asthma. Not effective during an acute asthma attack. Toxicity is rare.

CD 16, CD56, CD 2

methyldopa

prevents cholesterol reabsorption at small intestine brush border

INH
Sulfonamides

Primaquine
Aspirin
Ibuprofen
Nitrofurantoin

Dapsone
Naphtheline
Fava Beans

interferes w/60s, inhibiting protein synth

Zileuton -- 5 LOX pathway inhibitor. Blocks conversion of arachiodonic acid to leukotrienes

Zifirlukast, montelukast -- block leukotriene receptors. Especially good for aspirin induced asthma.

Gemfibrozil
--fibrate

upregulate LDL --> increased TG clearance

myositis, hepatotoxicity, cholesterol gallstones

Monobactam (aerobic)
Aminoglycosides (aerobic)
Polymyxin

chloramphenicol
benzene
NSAIDs
PTU
methimazole
alkylating agents

Edema factor is adenylate cyclase that causes increased levels in intracellular cAMP in phagocytes and formation of ion-permeable pres in membrane. Decreased phagocytosis, causes edema, kills cells

T8 -- IV
T10 -- esophagus, vagus (2 trunks)
T12 -- aorta, thoracic duct, azygous vein

diaphragm innervated by C3, 4, 5

Phenytoin
MTX
Sulfa

Strongyloides stercoralis

Vancomycin
Clindamycin
Linezolid

Halothane
Valproic Acid
Acetaminophen
Amanita phalloides

Both have decreased O2, CO2

high alt -- increased pH, resp alk; decreased Hb saturation

acclimation -- decreased pH, renal compensation; increased Hb concentration (epo)

All the NRTIs cause lactic acidosis

+ PN -- didianosine, stavudine, zalatabine

Increased cAMP in phagocytes, hemolysis. ADP ribosylates G

(a) Fat embolus – associated with
i. long bone fractures
ii. liposuction
(b) Pulmonary embolus – chest pain, tachypnea, dyspnea
i. DVT:
ii. stasis
iii. hypercoagubility
iv. endothelial damage
v. can use d-dimers to test

nephrotox (foscarnet as well)

Nephrotoxicity
Ototoxicity
Thrombophlebitis
Red Man Syndrome

Lactic acidosis
Megaloblastic Anemia (zidovudine)
Pancreatitis (ddt, zalcitabine, stvd)
Peripheral Neur (ddt, zalcitabine, stvdn)

Hepatic Steatosis (fatty liver) -- zidovudine, stavodine

hypersensitivity -- abacovir

Histiocytosis X
proliferation of Langerhans cells, CD1a + birbeck granules (tennis-racket shaped)

PABA

PABA is needed to synth folate de novo. Sulfonamides inhibit dihydropteroic acid synthase (only in bacteria) to prevent synthesis of tetrahydrofolic acid.

Inhibits synthesis of guanine nucleotides by competitively inhibiting IMP dehydrog

use -- adult RSV, chronic help B

tox -- hemolytic anemia, severe tetratogen

Tetanus toxin is a neurotoxin. Zn2+ dependent protease that blocks release of inhibitory transmitters glycine & GABA = spastic paralysis

in addition to megaloblastic anemia, causes demyelination of spinal cord posterior columns and lateral corticospinal tracts) subacute combined degeneration of spinal tract =dementia, peripheral neuropathy

serum methylmalonic acid

hemorrhagic cystitis
conjunctivitis
pneumonia
febrile pharyngitis
diarrhea

most common primary adult brain tumor
- can cross corpus collusum (butterfly glioma)
- stain for GFAP
- pseudopalisading pelomorphic tumor cells (border central areas of necrosis and hemorrhage)

displace bilirubin from albumin, causing kernicterus

- 2nd most common primary brain tumir
- convexities of hemispheres, parasagittal resion
- arises from arachnoid cells external to brain
- spindle cells arranged in whorled patterd + psammoma bodies (laminated calcifications)

Nevirapine
Efavirenz
Delaviridine

rash, false pos cannibus

- 3rd most common primary brain tumir
- often locatlized to CN VIII = acoustic schwannoma
- cerebellopontine angle
- S-100 positive
- bilateral schwannoma associatedwith NF2
- alternating areas of Antoni A, Antoni B cells

Botulism toxin is Zn2+ dependent protease inhibiting release of Ach = flaccid paralysis

- rare, slow growing
- frontal lobes
- chicken-wire capillary pattern, "fried egg" appearance

phelezine
trancypromine

- posterior fossa
- GFAP
- benign, good prognosis, well circumscribed
- Rosenthal fibers (eosinophilic + corkscrew fibers)

inhibits bacterial dihydrofolate reductase.

megaloblastic anemia, leukopenia, granulocytopenia. alliviate with supplemental folinic acid (leucovorin rescue)

- very poor, highly malignant
- form of primitive neuroectodermal tumor
- can compress 4th ventricle, causing hydrocephalus
- rosettes

Depresses ectopic pacemakers in hypokalemia

- 4th ventricle (children), cauda equina (adults)
- hydrocephalus
- poor prognosis
- characteritic perivascular pseudorosettes

Specific enzymes called RAG1 and RAG2 (recombination activating genes) control VDJ recombination. These enzymes are encoded for by transposable elements of the DNA that probably originated from viruses.
RAG1 and RAG2 recognize specific sequences called recombination signal sequences (RSSs), arranged so that the enzymes "know" whether the gene being recombined comes before or after the signal sequence.

- cerebellar
- associated with von Hippel-Lindau syndrome when found with retinal angiomas
- can produce EPO --> secondary polycythemia
- foamy cells and high vascularity

recurrent UTI
Shigella
Salmonella
PCP

benign childhood tumor, confused with pituitary adenoma (can also cause bitempral heminopia)

most common childhood supratentorial tumor

derived from remnants of Rathke's pouch
calcifcation is common (tooth-enamel like)

tolterodine
darifenacin, solifenacin
trospium

The V and J gene segments recombine first. During recombination:
1. RAG binds to the RSS after the selected V segment, and before the selected J segment
2. Cleavage of the DNA
3. Optional insertion of random nucleotides in the DNA break, by an enzyme called TdT
4. Repair of the DNA by regular dsDNA break repair enzymes, to place the randomly selected V next to the randomly selected J

Effective in torsades de points and digtoxin toxicity

synthed by streptomyces virginae

A -- binds peptidyl transfer of 50S
B -- prevents protein chain extention

use for MRSA, VRE, strep and staph skin

SE: hepatotoxicity, pseudomembranous colitis

Alzheimer's
Multiple Infarcts

In the primary immune response, mostly mediated by IgM, AG/AB affinity is not very high. Then, the antibody undergoes a process called somatic hypermutation, which improves the AB/AG affinity. After undergoing somatic hypermutation, the antibodies undergo a process called switch recombination, in which the heavy chain, that defines the AB as G, M, E, etc. is exchanged.
Immunization with a single antigen will result in a monoclonal response. However, the monoclonal response will give rise to many different antibodies, due to mutations in the hypervariable region.
The process of VDJ recombination of T cells happens in the thymus and bone marrow.
The process of improving AB/AG affinity after cells encounter the AG happens in the spleen and lymph nodes, particularly, in the germinal centers.

B cells can also undergo a process called switch recombination, in which one class of antibody is exchanged for a different class (e.g. A for M, E, G, etc). This process is also mediated by AID. When AID introduces mutations in the "switch region," the result is a DNA break and deletion of the intermediary sequence.

albuterol

Zenker's diverticulum

B cells that have encountered antigens enter the dark zone of the germinal center. Cells proliferate in the dark zone, creating a clonal group of B cells. Then, specific mechanisms cause lots and lots of mutations to occur in the rearranged gene, resulting in the production of many different proteins--this process is called somatic hypermutation, and happens in the V segment of the gene.
Some of the proteins produced as a result of these mutations will be non-functional, and the cell will die. Most will give rise to a less effective AB. A small percent will give rise to a more effective AB, with higher AG affinity.
Dendritic cells sit in the light zone of the germinal center, presenting antigens on their surfaces. The clones that have generated the best antibodies compete with each other for binding to the dendritic cells.
Cells that bind the DCs receive survival signals. Cells that do not bind the DCs undergo apoptosis in the light zone. The presence of lots of apoptotic cells is what makes the light zone light.

Sepsis
Trauma
OB
Pancreatitis
Malignancy
Nephropaty
Transfusion

IgA (Berger's)

Lymphogranuloma venereum- only STD without ulcers

binds to 50 ribosomal subunit to inhibit translocation of peptidyl-RNA, inhibiting protein synthesis

i. likely causes bronchodilation by inhibiting phosphodiesterase, thereby decreasing cAMP hydrolysus
ii. usage limited b/c of narrow therapeutic index (cardiotoxicity -- increased HR, arrhythmia, neurotoxicity)
iii. metabolized by P-450
iv. blocks actions of adenosine (used for SVT)

B cells can also undergo a process called switch recombination, in which one class of antibody is exchanged for a different class (e.g. A for M, E, G, etc). This process is also mediated by AID. When AID introduces mutations in the "switch region," the result is a DNA break and deletion of the intermediary sequence.

decreased axonal conduction by preventating Na influx through Na channels

Multiple transfusions or hereditary HFE mutation (can result in CHF, "bronze diabetes," and increased risk of hepatocellular carcinoma)

decreased entry of Ca through T-type channels in thelamaic neurons (sensory motor relay, responsible for absence seizures)

Somatic hypermutation in the germinal centers is a very dangerous process, and can lead to mutations in protooncogenes that result in lymphomas.
99.9% of cells in the germinal centers undergo apoptosis, during which the DNA is chopped up. If a cell is "rescued" in the beginning of apoptosis, the high rate of mutations and recombinations can often lead to cancer. Hodgkin's is an example of such a cancer. Hodgkin's cells are B cells that have mutations making their Igs non-productive, which suggests that these cells were supposed to undergo apoptosis after their (normal) hypermutation was non-productive, and "by mistake," didn't. A large percentage of Hodgkin's cells contain the Epstein Barr virus, which stops apoptosis.

CNS depression -- drowsiness, sedation, nyastigmus

osteomalacia, megaloblastic & aplastic anemia

Gallstones
Ethanol
Trauma

Steroids
Mumps
Autoimmune disease
Scorpion sting
Hypercalcemia/hyperlipidemia
ERSP
Drugs (e.g. sulfa)

azithromycin

hypertrophic pyloric stenosis

Fabry's

trigeminal neuraligia
manic phase of bipolar

1-4 hours wavy myocyte fibers
4-24 hrs coagulative necros.
1-3 days neutrophilic infil.
3-7 days macrophages
7-28 days granulation tis.
months fibrotic scar

Gaucher's

Tay Sach
Niemann-Pick
Krabbe's

0-18 hours no gross change
18-24 hrs vague pallor and soft.
1-7 days yellow pallor
7-28 day central pall w/red bord
months white, firm scar

metachromic leukodystrophy

Hurler's -- has both
Hunter's -- mental
Scheie's -- corneal
I-cell -- may or may have mental retardation

barb
used for induction of anesthesia, short surg procedures
highly lipid soluble, rapid onset, decreased cerebral blood flow

redistributed in tissues, not metabolized

Hurler's
Scheie's

hunter's

blocks NMDA antagonists
- CV stimulation, increased blood flow, increased intracranial pressure
- dissociatice

metachromic leukodystrophy

esters (1 i)
amides (2 is)

Rheumatic fever--following a strep A infection, molecular mimicry develops between the M protein on the streptococcus and other proteins, expressed on the heart and brain. Autoantibodies begin to attack the myocardium, in the presence of pro-inflammatory cytokines. Cytotoxic T cells are triggered to destroy myocardial and valvular tissue.

NB: molecular mimicry is not the same thing as cross reactivity.
Molecular mimicry occurs when an autoreactive cell or antibody recognizes and destroys a self-structure on a pathogen or autoantigen.
Cross reactivity occurs when an autoreactive cell or antibody simply recognizes a self-structure on a pathogen or autoantigen.

Multiple sclerosis--an autoimmune disease of the CNS. In MS patients, myelin basic protein and myelin oligodendrocyte glycoprotein act as self-antigens and are attacked by macrophages and T cells. The T cell response in MS may be the result of a hep B infection, since hep B viral polymerase is very similar to MBP. According to this hypothesis, hep B polymerase induces a molecular mimicry mechanisms which triggers the T cells to start destroying host tissue.

Guillain-Barre syndrome--an immune-mediated disease of the PNS, in which autoantibodies attack the myelin sheaths and axons of peripheral nerves.
In many cases of Gullain-Barre, the disease follows an acute infection of the campylobacter jejuni bacterium. This infection results in the production of the autoantibodies that attack the myelin sheaths. One possible mechanism for this disease is that a lipooligosaccharide (LOS) on the bacterial cell wall is also present on the myelin sheaths, resulting in molecular mimicry.

block Na channels -- non ionized form crosses axonal membrane, activated & ionized inside where it binds to specific receptors on inner portion of channel

Fabry's

type C (the smaller diameter)

coadministration with a1 agonists for vasoconstriction in oder to decrease absorption into system, prolong effects and decrease toxicity

-- neurotoxicity, CV tox (bupivacaine)

cilstatin is inhib of renal dihydropeptidase, which ordinarily would inactivate imipenem in renal tubules

tubocuraine
--curonium

Krabbe's

nicotinic with zero efficacy, binds to a subunit, reversible with AChE (neostigmine)

progressive paralysis: face, lumbs, resp musckls
no effect on cardio, CNS, smooth muscle

Gaucher

rapid recovery; sade in hepatic or renal impairment
- spontaneous inactivation to laudanosine, which can cause seizure

Haem
E coli
Listeria
Proteus
Salmonella
enterococi

ultrashort acting b/c degreaded by plasma choliesterases

- Deficiency in mannose

- phosphorylation
no mannose 6 phosphate to target lysosomal proteins --> secretion out of cell instead of into lysosomal death by age 8

- increased corneal clouding, coarse facies, HSM, skeletal abnormalities, restricted

Succinylcholine (nicotine agonist)

- Phase I -- prolonged depolarization, fasciculations, flaccid paralysis

- Phase II -- desensitization

hyperkalemia, malignant hyperthermia

Rheumatoid arthritis can be treated by IL1 and TNFα blockers.
Remicade and humira are anti-TNFα drugs that are used to treat rheumatoid arthritis.
Enbrel is another drug, made from an antibody that blocks binding of TNFα to its FcRII receptor.

Dantolene

prevents Ca from sarcoplasmic reticulum of skeletal muscle

car, tic, piperacillin
imipenem/cilstatin
aztreonam
fep, fop, taz
fluoroquinolones
aminoglycosides

- mu opiod receptor antagonist
- resp depression, CNS depres
- minimal effect on heart but vasodilation
- circular constricts
- nausea, vomiting, increased histamine

Increased Ca, Phos
Normal alk phosphate
Decreased PTH

antimuscarinic but no myosis
no GI GU GB spasm
causes seizures b/c metablizes into DRI

Decreased Ca
Increased PTH
Increased phos (b/c can't excrete it)

- converted inDA by AAAD once crosses BBB
- always given with carbidopa (non comp inhib of AAAD,incresing bioavailability)

side -- dyskinesia, on off, psychosis

neurotoxicity, nephrotoxicity

- inhib COMT,enhance levodopa uptake and efficacy (prevents degradation)

_ TOLCAPONE hepatotoxic

an inflammation of the small blood vessels that typically affects the upper respiratory tract and kidneys. This disease is characterized by the presence of anti-neutrophil cytoplasmic antibodies that activate neutrophils, causing oxidative bursts the result in the destruction of the endothelium.

- selective MAOb inhib (decreases central doapmine degradation)
- no tyramine interactions
- initial treatment and adjunct to levodopa
- side effects -- dyskinesia, psychosis, INSOMNIA b/c metabolized to amphetamine

erection -- parasympathetic

emission -- sympathetic; hypogastric nerve

ejaculation -- visceral and somatic nerves (pudendal)

decreased tremor and rigidity, anti-muscarinic,atropine-like

because insulin:
1. Enhances sodium reabsorption in the kidneys
2. Stimulates the sympathetic nervous system by activating sympathetic centers in the brain
3. Increases the pressor response to angiotensin II
4. Increases angiontensin II production
5. Increases sodium sensitivity
6. Stimulates smooth muscle proliferation
7. Increases intracellular Ca

1. lorazepam

2. phenytoin (decreases Na current in cortical neurons)

maintain germ pool and produce primary spermatocytes

line seminiferous tubules

secrete inhibin --> inhibit FSH

secrete androgen-binding protein (ABP) --> maintain levels of testosterone

tight junctions -- blood testes barrier (isolate gametes from attack)

support and nourish developing spermatozoa, regulate spermatogenesis

produce MIF

interstitium

Testosterone and androstenedione are converted to estrogen in adipose tissue and sertoli cells by enzyme aromatase

Inhibits HPG axis, leading to decreased intracellular testosteronem leading to decreased testicular size and azoospermia

fever/chills
hypotension
nephrotoxicity
arrhythmias
anemia
IV phlebitis

reduce toxicit with hydration or liposomal Amp

Leydig cell makes testosterone, but sertoli cells secrete ABP, which helps maintain testosterone in area

yolk sac
embryonal

inhibits cell wall synthesis by inhib b-glucan

Invasive aspergillosis

choriocarcinoma
embryonal

Glutamate (excitatory) receptor in the brain, voltage-dependent activation, a result of ion channel block by extracellular Mg2+ ions. This allows the flow of Na+ and small amounts of Ca2+ ions into the cell and K+ out of the cell. Involved in learning and memory.

Once leukocytes marginate, rolling & adhesion.
1. Induction of adhesion molecule on endothelium more sticky
2. Weak binding mediated via selectins and will slows the WBC by rolling. P-selectins are made de novo and bind to carbs.
3. Strong binding mediated via integrins (LFA 1), which cause firm adhesion. Expressed on leukocutes.

Inhibitory neurotransmitter.

1. GABAa receptor increases Cl conductance and is the site of action for benzos and barbituates

2. GABAb receptor increases K conductance

testicular lymphoma

Integrins are heterodimers of alpha and beta chains. Firm adhesion will only occur after conformational change of integrins. Though constantly expressed by leukocutes, they are expressed in inactive form. Dur to cytokines and chemokines (lie CXCL8) will bind to receptor, and integrin will become activated and undergo conformational change.

Frontal Lobe Lesion– Disinhibition and deficits in concentration, orientation, and judgement; may have reemergence of primitive reflexes.


Right Parietal Lobe Lesion – Spatial neglect syndrome (agnosia of the contralateral side of the world)

cyrptococcal meningitis in AIDSs patients and candida

seminoma

Leukocyte Adhesion Deficiency: Defect in beta2, recurrent infections, impaired wound healing. (integrin problems)

Neutrophils cannot be recruited to site of infection. If there is no full stop, they cannot get out of vessel.

Tabes Dorsalisis the degeneration/demyelination of dorsal columns and dorsal roots due to tertiary syphilis, resulting in impaired proprioception and locomotor ataxia. Associated with Charcot'sjoints, shooting (lightning) pain, Argyll Roberton pupils (reactive to accomodation but not light), absence of deep tendon reflexes, positive Romberg, and sensory ataxia at night.

Positive rombert because dorsal columns carry info of position (proprioception), vibration, and discriminitive touch.

Embryonal

phenytoin

furosemide, thiazide

corticosteroids
heparin

1) opoid analgesic
2) used with other CNS depressants during general anesthesia

selectively inhibits plasmodial DHFR. drug of choice for toxoplasmosis when combined with sulfadiazine

1) used for rapid anesthesia induction and short procedures
2) less postop nausea than thiopental
3) potentiates GABAa

expired tetracycline
heavy metal exposure
Wilson's

methicillin
NSAIDs
furosemide

inhibits enzymes involved in eergy metabolism. No CNS involvement (like melarsoprol)

Work on the a1 receptor (increases vascular SM contraction, papillary dilator muscle contraction, intestinal and bladder sphincter muscle contraction)

1. epinephrine -- decreases aueous humor secretion, causes mydriasis
2. brimonidine -- decreases aqueous humor, no dilation

buproprion
imipenem/cilstatin
INH

Timolol -- decreases aqueous humor secretion

It is at its maximum size at puberty, and gets smaller at maturity.

Acetazolamine -- decrease aqueous humor secretion due to decreased HCO3- (via inhibition of carbonic anhydrase in the the proximal convoluted tubule)

forms free radicals

1. Direct
- pilocarpine (emergencies)
- carbachol

2. Indirect
- physiostigmine
- echothiopate

Decrease outflow of aqueous humor by contracting ciliary muscle and open trabecular meshwork

DM I
SLE
RA

Lantanoprost (PGF2a) -- decreased outflow of aqueous humor

HCV

inhibits glycolysis at PFK reaction

Hodgkin's lymphoma

It inhibits transpeptidase, which cross links PDG cell wall of gram positive bacteria.

Cox B (can also cause asceptic meningitis)

blocks plasmodium heme polymerase, leading to accumulation of toxic hemoglobin breakdown products that destroy organism

1. ALL
2. cerebellar medulloblastoma

cyclins are regulatory proteins that control cell cycle events. They kind to and activate CDK which phosphorylate target proteins to drive the cell cycle.

When jon is completes, cyclins are degrade by ubiquitin protein ligase

p21 binds to and inactivates cyclin-cdk complexes so that the cell cycle may not continue. regulated by p53.

cyclin D activates cdk4, which phosphorylates Rb. Rb is released from transcription factor E2F. With E2F unbound, the cell is free to transcribe/synthesize components needed for progression through the S phase (cyclin E, DNA polymerase, thymidine kinase, DHFR)

cyclin E binds cdk2, and the cell is allowed to progress into S phase

i. nicotinic antagonist
ii. ganglionic blocker. Used in experimental models to prevent vagal reflex responses to changes in BP-- e.g., prevents reflex bradycardia caused by NE
iii. severe orthostatic hypotenison, blurred vision, constipation, sexual dysfunction

stimulates nicotinic receptors at NMJ. contraction occirs, followed by depolarizing-induced paralysis. No effect on tapeworms or flukes.

cyclin A - cdk 2 --> mitotic prophase

cyclin B - cdk 1 complex activated by cdc25, which leads to the breakdown of the nuclear envelope and initiates mitosis

microvilli
adherins
cytokenesis

Glycine and succinyl CoA comes together and interact with ALA synthase to form ALA.

intensifies GABA-mediated neurotransmission and causes immobilization. Does not cross BBB

CT (fibroblasts, leukocytes, endothelium)

neurons

transmembrane receptors that bind an extracellular ligand then intracellularly transfer a phosphate group from ATP to selected tryosine side chains on specific cellular proteins including itself (autophosh). The first step in the signaliing cascade that is initiated by tyrosine kinase receptors is autophorsphoryl

1. activated phospholipase C --> IP3/Ca and DAG/PKC

2:
adaptor protein
Ras activating protein
active Ras protein
activation of protein kinase 1-3
affected target

mech -- inhibits synthesis of guanine nucleotides by competiviely inhib IMP dehydrogenase.

use -- RSV, chronic hep C, arenavrisu

tox -- hemolytic anemia, severe tetratogen

decreased ATP synthesis

cellular swelling (no ATP --> impaired Na/K pump)

nuclear chromatin clumping

decreased glycogen

fatty change

ribosomal detatchment (decreased protein synthesis)

physical support, repair, K metabolism, removal of excess neurotransmitter, maintanence of BBB. reactive gliosis in response to injury. astrocyte marker -- GFAP

nuclear pyknosis, karyolysis, karyorrhexia

Ca influx --> caspase activation

plasma membrane damage

lysosomal rupture

mitochondrial permeability

CNA phagocytes. Mesodermal origin. respond to tissue damage by differentiating into large phagocytic cells.

HIV-infected microglia fuse toform multinucleated giant cells in the CNS

viral DNA polymerase inhib that binds to pyrophosphate-binding site of enzyme. Does not require thymidine kinase activation.

Used for CMV retinitis (gangciclovir too)

Hematotoxicity, nephrotoxicity

each oligodenfrocyte myelinates multple CNA axons. predom in white matter. Look like fried eggs, destroyed in MS

PGI

decreased platelet aggregating
decreased uterine tone
vasodilation

each cell myelinates only 1 PNS axon. Also promite axonal regeneration. Derived from neural crest. create new pathways

destroyed in Gullain-Barre syndrome

PGE2

increased pain
increased uterine tone
increased temp
decreased vascular tone

C -- slow, unmyelinated fivers

A(d) -- fast, myelinated

Located in all skin, epidermis, some viscera

senses pain and termperature

leukopenia, neutropenia, thrombocytopenia, renal toxicity

located in glabrour (hairless) skin

position sense, dynamic fine touch (e.g. manipulation), adapt quickly (sends signal only at the beginning and end of a stimulus)

increased platelet aggregation
vasoconstriction

Located in deep skin layers, ligaments, and joints

vibration and pressure

lamins

located in hair follicles

position sense, static touch (e.g. shapes, edges, textures), adapt slowly (continuous)

signal rich in arginine, lysine, or proline

1. endoneurium -- invests single nerve fibers, inner (inflammatory infiltrate in Guillan-Barre)

2. Perineurium (permeability barrier) -- surrounds a fascicle of nerve fibers. must be rejoined in microsurgery for limb reattachment

3. epineurium -- dense connective tissue that surrounds entire nevers (fascicles and blood vessels)

reticular formation
locus ceruelus (makes NE)
raphe nuclei (makes serotonin)

mediates consciousness and attentiveness

1. locus ceruleus
2. ventral tegmentum and SNc
3. raphe nucelus
4. basal nucleus of meynert
5. nucleus accumbens

ventral tegmentum and SNc

raphe nucleus

basal nucleus of Meynert

nucleus accumbens

B6 to turn glutamate into GABA

anterior, preoptic

ADH -- supraoptic nucleus

oxytocin -- paraventricular nucleus

dentate nucleus and basal ganglia --> supplementary motor cortex

act as agonists at opioid receptors (m= morphone, d=enkephalin, kappa=dynorphin) to modulate transmission -- open K channels, close Ca2+ channels, decreased synaptic transmission. Inhibits release of ACh, NE, 5-HT, glutamate, substance P

basal ganglia --> prefrontal, premotor, and orbital cortices

addiction
respiratory depression
contipation
miosis
additive CNS depression

treat with naloxone

mamillothalamic tract --> cingulate gyrus (part of papex circuit)

Heparin is an indirect anticoagulant. Today, low molecular weight heparin, called Enoxaparin is used. Low molecular weight heparin can be given subcutaneously, twice daily, unlike regular heparin, which needs to be given via IV.
The dose of low molecular weight heparin needs to be adjusted if the patient has renal dysfunction.
Heparin is contraindicated in a patient with a risk of bleeding. In such a patient, there is no alternative treatment option, and the bleeding needs to be controlled before heparin can be used.

The higher the TIMI risk score, the greater the efficacy of low molecular weight heparin.

Signs of intoxication include:
1. impaired judgement
2. pupillary dilation
3. prolonged wakefulness and attention
4. delusions
5. hallucinations
6. fever

Signs of with withdrawal include:
1. stomach cramps
2. hunger
3. hypersomnolence

Factor Xa is necessary for thrombin activation. Factor Xa inhibitors block thrombin by blocking Xa, acting much closer to thrombin on the coagulation cascade than heparin does, which makes them more selective, and less prone to adverse side effects.
Fondaparinux--a Xa inhibitor.

Beck triad --
hypotension
increase JVP
distant heart sounds

ADP is present in the circulation, and rises in inflammatory and thrombotic states. Platelets have an ADP receptor, which ADP can bind to, to active the platelet.
Drugs that block the ADP receptor (most are thienopyridines) are the mainstay of ACS treatment.
Thienopyridines bind covalently to the ADP receptor, irreversibly inhibiting it.

ADP antagonists include:
1. Clopidogrel (Plavix)
2. Ticlopidine
3. Prasugrel
4. Ticagrelor

(a) Phenylalanine → tyrosine → DOPA → Dopamine → NE → Epinephrine
i. tyrosine –> thyroxine
ii. Dopa → melanin

hyperpolarize vascular smooth muscle > arterial vasodilation

Melatonin
Niacin (needs B6) --> NAD, NAHP

Inhibition of potassium channels (Class III activity) widens the action potential, leading to a prolonged QT interval on the electrocardiogram. Such an effect is associated with increased risk of developing life-threatening ventricular tachyarrhythmias

a.
Liver: Biochemical abnormalities in liver function have occurred with the HMG CoA reductase inhibitors. Therefore, it is prudent to evaluate liver function and measure serum transaminase levels periodically. These return to normal on suspension of the drug. [Note: Hepatic insufficiency can cause drug accumulation.]

b. Muscle: Myopathy and rhabdomyolysis (disintegration or dissolution of muscle) have been reported only rarely. In most of these cases, patients usually suffered from renal insufficiency or were taking drugs such as cyclosporine, itraconazole, erythromycin, gemfibrozil, or niacin. Plasma creatine kinase levels should be determined regularly.

3 months

7-9 months

15 months

12-24 months

(a) Inadequate hepatic copper excretion and failutre of copper to enter circulation as ceruloplasmin
(b) leads to copper accumulation, especially in liver, brain, vornea, kidneys, and joints

24-36 months

i. asterixis (wrist tremor)
ii. basal ganglia degeneration (parkinsonian symptoms)
iii. ceruloplasmin decrease, cirrhosis, corneal deposits, copper accumulation, carcinoma
iv. dementia, dyskinesia, dysarthria
v. hemolytic anemia

3 years

4 years

6 years

tricyclics
antihypertensives
SSRIs (may inhibit orgasm)

polyneuritis
symmetrical wasting

serotongergic predominance of raphe nuclei

high-output cardiac failure (dilated cardiomyopathy)
edema

due to PPRF (paramedian pontine reticular formation/conjugate gaze center)

Wernicke -- confusion, ophthalmoplegia, ataxia

Korsakoff -- memory loss (antero/retrograde), confabulation, personality changes

Can be caused by thiamine (B1) deficiency or mamillary body lesion

waxing and waning level of consciousness with acute onset; rapid decrease in attention span and level of arousal. Characterized by acute changes in mental status, disorganized thinking, hallucinations (often visual), illusions, misperceptions, disturbance in sleep-wake cycle, cognitive dysfunction.
usually secondary to other illness (e.g. meningitis, CNS disease, infection, trauma, substance abuse/withdrawal)

presents abnormal EEG

gradual decrease in cognition with no change in level of consciousness. Characterized by memory deficits, aphasia, apraxia, agnosia, loss of abstract thought, behavioural/personality changes, impaired judgment. Patient is alert. No psychotic symptoms. more often gradual onset. Normal EEG.

Caused by Alzheimer's disease, vascular thrombosis/hemorrhage (may have acute/subacute onset), HIV, Pick's disease, substance abuse, CJD

irreversible loss of memory, loss of intellectual abilities

fixed, persistent, nonbizarre belief system lasting > 1 month. Functioning otherwise not impaired, Often self-limited

acts as hallucinogen combined with an emphetamine; effects begin in 45 minutes and last 2 hours

acute -- dehydration, fatigue
chronic -- destruction of the serotonin receptors (increased impulsiveness); destruction of connection b/w brain cells (memory gaps)

Anterior -- cooling, parasympathetic

Posterior -- heating, sweating

Imipramine
Amitriptyline
Desipramine
Clompramine

sedation, a-blocking side effects, atropine-like (anticholinergic) side effects (tachycadia, urinary retention).

tertiary TCAs (amitriptyline) have more anticholin effects than secondary TCAs (nortriptyline)

Desipramine is the least sedating and has lower seizure threshold. gives energy before stabilizes mode = suicide window, sexual dysfunction

convulsions
coma
cardiotoxicity
respiratory depression
hyperpyrexia
confusion and hallucination in elderly

withdrawal should be gradual --> akathisia, hyskinesia, anxiety, sweating, dizziness, vomiting, cholinergic and depression rebound

receives contralateral cortical input via middle cerebellar peduncle and ipsilateral proprioceotive information via inferior cerebellar peduncle. Input nerves = climbing and mossy fibers

provides stimulatory feedback to contralateral cortex to modulate movement. Output nerves = Purkinhe fibers output to deep nuclei of cerebellum, which in turn output to cortext via cerebellar peduncle.

Fast Gerbils Exercise Daily (M-->L)
Fastigial, Globose, Emboliform, Dentate

with any drug that increases serotonin (e.g. MAO inhibitors) -- hyperthermia, muscle rigidity, CV collapse, flushing diarrhea, seizure

Treatment -- take med away, cyprohetadine if severe

dentate
emboliform
globose
fastigial

venlafaxine, duloxetine (depression + pain)

inhibit seronin and NE reuptake

use: depression. venafaxien is also used in generalized anxiety disorder; duloxetine is also indicated for diabetic peripheral neuropathy, greater effect on NE

tox: increased BP most common; also stimulant effects, sedation, nausea

Lateral -- voluntary movement of extremities

Medial -- balance, truncal coordination, ataxia, propensity to fall toward injured side

Also used for smoking cessation. Increased NE and DA via unknown mech.

tox -- stimulant effects (tachy, insomia), headaches, seizure in bulimic patients.

Important in voluntary movements and making postural adjustments.

receives cortical input, provides negative feedback to cortex to modulate movement

striatum -- putamen + caudate
lentiform -- putamen + globus pallidus

a2 antagonist (increased release of NE and serotonin) and potent 5-HT receptor antagonist.

tox -- sedation, increased apetite, weight gain, dry mouth

Excitatory aka direct pathway

1. DA on D1 receptor stimulates striatum (caudate -- cognitive; putamen -- motor)

2. Striatum releases ACh, stimulating release of GABA and substance P

3. GABA, substance P inhibits globus pallidus interna and substantia nigra reticulara

4. Inhibition of GPi and SNr leads to inhibition of the thalamus, which stimulates the cortex

blocks NE reuptake.

tox -- sedation, orthostatic hypotension

Inhibitory aka indirect pathway

1. DA binds to D2 receptor, which inhibits the striatum

2. Inhibition leads to release of ACh, which will lead to release of GABA and enkephalin

3. GABA and enkephalin inhibit GPe, which in turn inhibits the subthalamic nucleus

4. STN stimulates the GPi, which will inhibit the thalamus, which stimulates the cortex

primarily inhibits serotonin reuptake. used for insomnia, as high doses are needed for antidepressant effects.

tox -- sedation, nausea, priaprism, postural hypotension, strong a1 block

Produced at base of lumbs in zone of polarizing activity. Involved ini patterning along anterior-posterior axis.

Mediates ectoderm; mutation --> holoencephaly

Produced at apical ectodermal ridge (thickened ectoderm aat distal end of each developing limb). Necessary for proper organization along dorsal-vebtral axis.

Produced at apical ectodermal ridge. Stimulates mitosis of underlying mesoderm, providing for lengthening of limbs.

Mut FGF3 = achondroplasia

Involved in segmental organization of embro in craniocaudal direction. Blueprint for skeletal morphology.

Code for transcription regulators.

Mutation in HOX 13 --> synpolydactly

retinoic acid alters HOX gene expression

absence of digits, multiple anomalies
(stop cell growth)

CN VIII toxicity

rd week -- yolk sac forms allantois, which extends into urogenital sinus. Allantois becomes urachus, a duct b/w bladder and yolk sac.

Failure to obliterate:
1. patent urachus -- urine drainage from umbilicus
2. vesicourachal diverticulum -- outpouching of bladder

euphoria
auditory hallucinations
delusions
thought disorders
poor verbal comprehension

HAPPY PSYCHOTIC

7th week -- obliteration of vitelline ducts (omphalomesenteric duct), which connects to midgut lumen

vitelline fistula -- failure of duct to close --> meconium discharge from umbilicus

Meckel's diverticulum may have ectopic gastric mucosa --> melena and periumbilical pain

dysphora
irritability
decreased visual and musical abilitu

neural crest migration from hindbrain through pharyngeal arches --> truncal and bulbar ridges that spiral and fuse to form the AP septum --> ascending aorta and pulmonary trunk

pathology -- tnrasposition of great vessels (failure to spiral), tetralogy of Fallor (skewed AP septum development), persistent TA (partial AP septum development)

intellectual processing of sensory information
left -- languag (dom)
right -- visual/spatial (nondom)

1. ventricular chamber lays anteriorly in S shapes heart tibe --> muscular ventricular septum forms which begins to divide the ventricles

2. truncoconical swellings (ridges) of TA meet, fuse, and zip (both superiorly and inferiorly) in a 180 degres turn to form from the spiral septum (aka AP septum)

3. Inferior portion of spiral septum meets with muscular ventricular septum to divide the ventricles and form the aorta and pulmonary arties

agraphia
acalculi
finger agnosia
R/L disorientation

1st -- maxillary

2nd -- stapedal artery and hyoid

3rd -- common carotid and proximal part of internal carotid

4th -- on left, aortic arch; on right, proximal part of right subclavian

6th -- proximal part of pulmonary arteries and (on left only) ductus arteriosis

denial of illness
construction apraxia (difficulty outlining objects)
neglect of opposite side

Y (3-8 wk)
L (6-30 wk)
S (9-28 wk)
B (28 wk onward)

a/w materal lithium use
tricuspid leaflets are displaced into RV, hypoplastic RV, tricuspid regurg or stenosis

80% hjave a patent foramen ovale with a R --> L shunt

dilated RA = increased risk of SVT and WPW

physical exam -- widely split S2, tricuspid reurg

Rx -- PGE, digoxin, diuresis, pronpanolol for SVT

2st -- external auditory meatus

2nd - 4th -- temporary cervical sinuses, which are oblierated by proliferation of 2nd arch mesenchyme

spinal cord extends to lower borders of L1 - L2

subarachnoid space extends to lower border of S2

branchial cleft cyst within lateral neck
don't move with swallowing

bicep = C5 nerve root
tricep = C7 nerve root
patella = L4 nerve root
achilles = S1 nerve root

M's & Ts
- mastication
- mylohyoid
tensor tympani, etc
anteriot 2/3 of tongue
trigmenial

S's
stapes
styloid
faSial

superior -- conjugate vertical gaze center

inferior -- auditory

Parinaud syndrome -- paralysis of conjugate vertical gaze due to lesion in superior colliculi (e.g. pinealoma)

pharyngeus

located in tegmentum portion of brain stem (b/w dorsal and ventral positions)

1. midbrain -- 3, 4
2. pons -- 5,6,7,8
3. medulla -- 9,10,11,12

neck, voice box
4th -- cricothyroid, superior laryngeal branch -- swallowing
6th -- all except crico; recurrent laryngral -- speaking

V1 (opthalmis -- nasociliary branch: levator palpebrae)

VII (temporal branch: orbicularis oculi)

omphalocele -- persistence of herniation of abdominal contents into umbilical cord, covrered by peritoneum;
- liver often protruding
- other annomalies common 50%5 GI, CV, GU, CNS, MS

gastroschisis -- extrusion of ab contents through ab folds; not covered by peritoneum
- liver never protruding
- other anomalies less common
- defect lateral to umbilicus

V1 (loss of reflex does not preclude emotional tears)

VII

SRY gene on Y chromosome -- produces TDF.

note that MIF is secreted from Sertoli cells -- suppresses development of paramesonephric ducts

Males -- glans penis
Female -- glas clit

Males -- corpus cavernosum, spongiosum
Females -- vestibular bulbs

Males -- Bulbourethral glands
Females -- Greater vestibular glands

Males -- prostate
Females -- urethral and paraurethral glands of Skene

IX

IX, X

Male -- ventral shaft of penis
Female -- Labia minora

visceral sensory information (e.g. taste, baroreceptors, gut distention)

VII, IX, X

Males -- scrotum
Females -- labia majora

motor innervation of pharynx, larynx, and upper esophagus (e.g. swallowing, palate elevation)

IX, X, XI

Female -- ovarian ligament + round ligament of uterus

Male -- anchors tests within scrotum

males -- obliterated

females -- tunica vaginalis

CN II - VI -- through sphenoid bone

1. optic canal -- CN II, opthalmic artery, central retinal vein)

2. superior orbital fissure -- CN III, IV, V1, VI, opthalamic vein, sympathetic fibers

3. foramen rotundum -- V2

4. foramen ovale -- V3

5. middle meningeal artery

Dysgenesis of seminiferous tubuls --> decreased inhibit, which increases FSH

Abnormal Leydig cell function --> decreased testosterone --> increased LH and estrogen

posterior cranial fossa (CN VII - XII) -- through temporal or occipital bone

1. internal auditory meatus -- VII, VIII

2. jugular foramen -- IX, X, XI, jugular vein

3. hypoglossal canal -- CN XII

4. foramen magnum -- spinal roots of CN XI, brain stem, vertebral arteries

decreased estrogen, increased LH, FSH

opthalmogplegia
opthalmic and maxillary sensory loss

nerves that control extraocular muscles (V1/2) pass through the cavernous sinus

increased LH
decreased FSH
increased estrogen, increased testosterone

lesion of motor cortex or connection b/w cortex and facial nucleus

contralateral paralysis of lower face only, since upper face reveibes bulateral UMN innervation

a -- glucagon (peripheral)
b -- insulin (central)
d -- somatostatin (interspersed)

1. increased glucose transport
2. increased glycogen synthesis and storage
3. increased triglyceride synthesis and storage
4. increased Na retention (kidneys)
5. increased protein synthesis (muscles)
6. increased cellular uptake of K and amino acids

complete destruction of the facial nucleus itself or its branchial efferent fibers (facial nerve proper)

peripheral ipsilateral facial paralysis with inability to close eye on involved side

can occur idiopathically, gradual recovery in most cases

It converts cholesterol to pregnenolone.

1. ACTH increases desmolase
2, Ketoconazole decreases desmolase

AIDS
Lyme disease
Herpes simplex
Sarcoidosis
Tumors
Diabetes

- autosomal dominant
- hypocalcemia
- short stature
- mental retardation
- shortened 4/5th digits
- obesity

treat with Ca and vit D supplementation

increase in intracranial pressure --> elevated optic disk with blurred margins, bigger blind spot (can be seen in hydrocephalus)

secondary hypoparathyroidism
High PTH
Low Ca

1. constriction -- pupillary sphincter muscle (circular) parasympathetic; innervated by CN III from Edinger-Westphal nucleus --> ciliary ganglion

2. Dilation -- radial muscle (aka pupillary dilator muscle) sympathetic. Innveration -- T1 preganglionic sympathetic -> superior cervical ganglion --> postganglionic sympathetic --> long ciliary nerve

hypoparathryoidsm
Low PTH
Low Ca

retinal necrosis + edema --> atrophic scar

hyperparathyroidism
High PTH
High Ca

systemic inflammation (e.g. Reiter's)

PTH-independent hypercalcemia
Low PTH
High Ca

ciliary muscle contracts (zonular fibers relax --> lens relaxes --> more convex)

remnants of Rathke's pouch, visual field defect, suprasellica

can be confused with prolactinoma

ciliary muscle relaxes (lens flattens)

inhibit phospholipase A2, which is the enzyme that liberates arachidonate from membrane phospholipids, providing precursor for prostaglandins and leukotrienes.

inhibit IL-2, which inhibit proliferation of T cells

sclerosis and decreased elasticity cause lens shape to change

Increases gluconeogenesis -- decreases the production of F2,6BP, decreasing phosphofructokinase.

Increases lipolysis -- ketoacids (b-hydroxybutyrate, acetoacetate) are produced from acetyl CoA, which results from fatty acid degeneration

Increases urea production

acute, painless monocular loss of vision; pale retina and cherry-red macula (has its own blood supply -- choroid artery)

squamous cell carcinoma
renal cell carcinoma
breast carcinoma

renal cell carcinoma
hemangioblastoma

dilator/radial muscle
(a1 --> mydriasis)

sphincter/circular/constrictor muscle
(M3 --> miosis)

ciliary muscle (M3 --> accommodation)

1. Influenza A & B
2. MMR
3. Polio
4. Rota
5. Varicella, Zoster
6. Adeno
7. Smallpox
8. Yellow Fever

1. Hep A
2. Flu A & B
3. Polio
4. Rabies

1. Selectins -- expressed in WBCs to mediate formation of weak bonds.
P selectins stored in endothelial cells and expressed upon the expression of CXCL8.
E selectins are synth'ed de novo.

2. Integrins -- mediate formation of strong bonds. on WBCs.
LFA1 binds to ICAM on endothelial.

painless, bilateral opacifications of lens --> decrease in vision

Risk: age, smoking, EtOH, sunlight, classsic galactosemia, galactokinase deficiency, diabetes (sorbitol), trauma, infection

MS
Hay feber
SLE
Goodpasture

bilateral small pupils that constrict when the patient focuses on a near object (they “accommodate”), but do not constrict when exposed to bright light (they do not “react” to light).

no direct or consequential light reflex; lesion in pretectal nuclei

rheumatoid arthritis
DM type I

lesion of afferent limb of pupillary light reflex; diagnoses made with swinging flashlight
1. affected pupil not fully constrict
2. normal pupil constriction
3. shine light immediately again in affected --> apparent dilation of both pupils b/c stimulus carried through CN II weaker

pernicious anemia
Hashimoto's

steroid-responsive nephrotic syndrome

Meyer's loop -- inferior retina; loops around inferior horn of lateral ventricle

Dorsal radiation -- superior retina; takes shortest path via internal capsule

a) X-linked recessive (increased in boys)
b) defect in BTK, a tyrosine kinase gene → block B-cell differentation/maturation
c) presents as recurrent bacterial infections after 6 months (decreased maternal IgG) due to opsonization
d) labs show normal pro-B, decreased maturation, decreased number of B cells, decreased immunoglobins of all classes

unilateral; 4-72 hours of pulsating pain with nausea, photophobia, or phonophobia. +/- "aura" of neurological symptoms before headache, including visual, sensory, speech disturbances/ Due to irritation of CN V and release of substance P, CGRP, vasoactive peptides.

Treat -- propanolol; NSAIDs; sumatriptan for acute migranes

a) defective CD40L on helper T cells = inability to class switch
b) severe pyogenic infections early in life
c) increased IgM, very low IgG/A/E

bilateral; > 30 minutes of steady pain. Not aggravated by light or noise; no aura

a) defect in isotope switching → deficiency in specific class of immunoglobulins
b) sinus and lung infections, milk allergies and diarrhea, anaphylaxis on exposure to blood products with IgA
c) IgA deficiency most common
d) failure to mature into plasma cells, decreased secretory IgA

a) defect in B-cell maturation; many causes
b) can be acquired in 20s-30s
c) increased risk of autoimmune disease, lymphoma, sinopulmonary infections
d) labs show normal number of B cells; decreased plasma cells, immunoglobin

a) 22q11 deletion, failure of 3rd and 4th pharyngeal pouch to clse
b) presents with tetany (hypocalcemia), recurrent viral/fungal infections (T-cell deficiency), congenital hear and great vessel defects
c) because thymus and parathyroid fail to develop, labs show decreased T cells, PTH, and Ca

a) decreased Th1 response
b) present as disseminated mycobacterial infections
c) decreased IFN-gamma

a) Th cells fail to produce IFN-gamma → inability of neutrophils to respond to chemotactic stimuli
b) presented as FATED
1) coarse Facies
2) cold, noninflamed staphylococcal Abscesses
3) retained primary Teeth
4) increased IgE
5) Dermatologic problems (eczema)
c) lab shows increased IgE

a) several types: defective IL-2 receptor (most common, X-linked), adenosine deaminase deficiency, failure to synthesize MHC II antigens
b) presents are recurrent viral, bactieral, funal and protozoal infections due to both B- and T-cell deficiency
c) treat with bone marrow transplant
d) labs show decreased IL-2R, decreased T-cell activation; increased adenin = toxic to B and T cells; decreased dNTPs, DNA synthesis

a) defect in DNA repair enzymes
b) Triad: cerebellar defects (ataxia), spider angiomas (telangiectasia), IgA
c) labs show IgA deficiency

a) X-linked recessive defect, progressive deletion of B and T cells
b) presents with TIE triad
Thrombocytopenic purpura
Infections
Eczema
c) labs show increased IgE, IgA; decreased IgM

lactic acidosis with hepatic steatosis

interfere with reverse transcriptase though competitive inhibition. Must be phosphorylated by thymidine kinase

ZDV (tox -- megaloblastic anemia)

didanosine
stavudine

bind directly to RT

Nevirapine
Eavirenz
Delaviridine

rash, bone marrow suppression, peripheral neuropathy

chronic hep B, C
Kaposi's sarcoma

MS

NADPH oxidase deficiency

1. Stepwise accumulation of nucleotide substitutions (RNA primed RNA polymerase, no proof reading, high error rate)

2. Genetic recombination during co-infection in same cell. E.g. two polio strains party it up together.

Zona occludens (tight junctions; claudins and occludins)
Zona adherins (intermediate--cadherins connect to actin)
Macula adherins (desmosome)
Gap junctions
Hemidesmosome

inflammation of extensor carpi ulnaris from forced extension and flexion of forearm at elbow (lateral epicondylitis). Pain over lateral epicondyle, radiating downward posteriorly.

degenerative injury due to repeated use; leads to tiny tears in tendons and muscles. think also: medial epicondylitis (gold elbow)

An embryological or childbirth defect affecting inferior trunk of brachial plexus (C8, T1); a cervical rib can compress subclavian artery and inferior trunk, resulting in thoracic outlet syndrome.

1. atrophy of the thenar and hypothenar eminences
2. atrophy of the interosseous muscles
. sensory deficits on the medial side of the forearm and hand
4. disappearance of the radial pulse upon moving the head toward the ipsilateral side

L2-L4

anterior hip dislocation

thigh adduction
medial thigh

L2-L4

pelvic fracture

thigh flexion and leg extension
anterior thigh and medial leg

Trauma to lateral aspect of leg or fibula neck fracture

foot eversion and dorsiflexion; toe extension; foot drop, foot slap, steppage gait
anterolateral and dorsal aspect of foot

L4-S2

knee trauma

foot inversion and plantarflexion; toe flexion

L4-S1

posterior hip location or polio

thigh abduction (positive Trendelenburg sign -- hip drops when standing on opposite foot)

L5-S2

posterior hip dislcation

can't jump, climb stairs, rise from seated position (can't push downward/inferiorly)

PED = peroneal everts and dorsiflexes; if injured, foot dropPED

TIP = tibial inverts and plantar flexes; if injured, cannot stand on TIP toes

Common peroneal and tibial nerve

When a depolarization (opening of voltage gated Ca channels) reaches the T-tubule, it stimulates the release of Ca from the SR trhough 1. the dihydropyridine receptor then 2. ryanodine receptor. Ca binds to troponin C, which binds to troponin T, which binds to tropomyosin. Binding to troponin T to tropomyosin pulls it off the myosin binding site, allowing myosin (release of ADP) to bind to actin, and stimulating muscle contraction. After contraction, Ca is pumped back into the SR, via SERCA.

H and I bands shorten, A remains same.

Actin is bound to alpha-actinin containing complexes, dense bodies. Calcium binds to calmodulin, which activates MCK. The MCK phosphorylates myosin, which then binds to actin and stimulates contraction.

Type I -- (e.g. postural weight bearing); slow twitch; red fibers due to increased mitochondria and myoglobin concentration (increased oxidative phosphorylation) --> sustained contraction.

Type II -- (e.g. purposeful movement) fast twitch; white fibers due to decreased mt and myoglobin concentration (increased anaerobic glycolysis); weight training results in hypertrophy of fast-twitch muscle fibers.

mesenchymal stem cells in periosteum

acid phosphatase and collagenase to resorb bone

in Howship lancunae

McCune-Albright Syndrome is a form of polyostotic fibrous dysplasia characterized by multiple unilateral bone lesions a/w endocrine abnormalities (precocious puberty) and unilateral pigmented skin lesions (cafe au lait spots)

swelling or wrists, fingers, ankles, knees, elbows
- ends of long bone have periosteal new bone formation (thickening)
- digital clubbing; angle of nailbed is lost
- arthritis of adjacent joints is commonly seen

a/w
1. bronchogenic carcinoma
2. chronic lung disease
3. cyanotic heart disease
4. IBD

common cause of knee pain in adults
pathophys: stress from quads during rapid growth causes inflammation of proximal tibial apophysis @ insertion of patellar tendon

can result in permanent knobby knees

a/w Gardner's Syndrome (FAP). New pioece of bone grows on another piece of bone, ften in skill, facial areas

Can extend into orbit sinuses (hyperostosis frontalis interna)

Interlacing trabeculae of woven bone surrounded by osteoblasts. < 2 cm and found in proximal tibia and femur. Most common in men < 25 years of age; tenderness worse @ night.

See lytic central lucency with sclerotic rim like osteomyelitis

same morphologically as osteoid osteoma (interlacing trabeculae of woven bone) but larger and found in vertebra

occurs most commonly at epiphyseal end of longbones. bulky masses, usually around knee, red bown mass w/cytic degeneration.

Peak incidence 20-49, locally aggressive benign tumor. Characteristic "double bubble" or soap bubble appearance on xray. Spindle shaped celles with multinucleated giant cells. 40-60% recurrence, 4% met to lungs.

most common benign bone tumor. Mature bone with cartilaginous cap. Usually in men <25 years of age. Commonly originates from long metaphysis. Malignant bone transfomation to chondrosarcoma is rate.

Single painfulmasses. If multiple, symmetric, and all over body, osteochondromatosis.

Benign catilaginous neoplasm found in intramedullar bone. Usually distal extremities (vs. chondrosarcoma), asymptomastic usually in the center of phyallanges.

1. Ollier disease -- nonherititary multiple in hands and feet. Present with pain and fracture, may undergo malignant transformation, ovarian carcinoma nd brain glioma.

2. Maffuci Syndrome:
Multiple enchondromas, soft tissue hemangioomas, incresed risk of maligant transformation --> ovarian and brain cancer

1. morning stiffness lasting > 30 min and improving with use, symmetric joint involvment, systemic symptomes (fever, fatigue, pleuritis, pericarditis, lymphadenopthy)

2. Caplan Syndrome -- a/w pneuomonociosis (chronic pleuritis with effusions)

3. Fetty Syndrome: RA + splenomegaly + neutropenia

15% develop Sjorgren's

Charcot Joint -- joint damage secondary to impared joint innervation leading to inability to sense pain

15% diabetes mellitus -- tends to damage the tarsometatarsal joint in midfoot

20-25% syringomyelia -- tends to damage shoulder, elbow, and wrist joints

10-15% tabes dorsalis -- tends to damage the hip, knee, and ankle joints

characterized by immune-mediated, widespread noncaseating granulomas and elevated serum ACE levels. Common in black females

restrictive lung disease
bilateral hilar lymphadenopathy
erthema nodosum
Bell's palsy
epithelial granulomas containing microscopic Schaumann and asteroid bodies
uveoparotitis
hypercalcemia (die to elevated 1a-hydroxylase-mediated vitamin D activation in epithelioid macrophages)

Treat -- steroids

Gammaglobulinemia
RA
ACE increase
Interstitial fibrosis
Noncaseating granulomas

Pain and stiffness in shoulders and hips, often with fever, malaise, and weight loss. Does not cause muscular weakness. Occurs in patients > 50 years of age; a/w temporal (giant cell) arteritis)

Findings: increased ESR, normal CK
treat -- predisone

sudden appearnace of multple seborrheic keratoses indicates an underlying malignancy (e.g. Gi, lymphoid)

Hyperpgimentation a/w pregnancy or OCP

deeper tissue injury, usually from anaerobic bacteria and s. pyogenes. results in crepitus from methane and CO2 production. Flesh eating bacteria

exotoxin destroys keratinocyte attachments in stratum granulosum only -- characterized by fever and generlized erythematous rash with sloughing of the upper layers of the epidermis. Seen in newborns and children.

Panniculitis
Inflammation of the subcutaneous tissue
Painful
Red
Occurs of anterior lower legs
Associated with systemic disease
Coccidiomycosis
TB
Strep pharyngitis
Sarcoidosis
UC
Pregnancy/OCP
Mycoplasma, yersinia, histoplasmosis

Treatment: Treat the underlying illness

Target lesions
Occurs on palms and soles
Treat by removing the underlying cause
If known Mycoplasma infection: macrolide or doxy
Stop the offending medication

2nd most common skin cancer
Precancerous lesion – actinic keratosis
Sun exposure → DNA damage → squamous dysplasia
Found on sun-exposed places
Can also occur in scar tissue (from a burn/surgery): called Marjolin’s ulcer
Minimal malignant potential, but way more than BCC
Ulcerated, scaly
Usually from the lower lip and downwards (except the ear)

Most common skin cancer
From the upper lip and upward
Minimal malignant potential
VERY locally aggressive
Caused by UV light
Found in hairy areas
Arises from......
Pearly papule, telangiectasias, umbilicated centre

ibuprofen, naproxen, indomethacin, ketorolac

reversibly inhibit COX-1/2. block prostaglandin synthesis

tox: renal damage, fluid retention, aplastic anemia, GI distress, ulcers

reversibly inhibit specifically th COX 2, found in inflammatory cells and vascular endothelium and mediates inflammation and pain, sparing COX-1, which helps maintain gastric mucosa.

RA, osteoartherities

tox: increased risk of thrombosis. sulfa algergy for celecoxib) less toxiv to GI mucosa

reversibly inhib COX, mostly in CNS. Inactivated peripherally

overdose produces hepatic necrosis; acetominophen metabolite depletes glutathione and forms toxic tissue adducts in liver. N-acetylcysteine is antidote -- regenerates glutathione

inhibit osteoclastic activity, reduce both formation and resorption of hydroxxyapatite.

malignancy-associated hypercalcemia, Paget's disease of bone, postmenopsusal osteoperosis

tox: corrosive esophagitis (except zoledronate), nausea, diarrhea, osteonecrosis of jaw

recombinant form of human TNF receptor that binds TNF

used for RA, proriasis, AS

(decoy receptor)

anti-TNF antibodu

Crohn's, RA, AS
--> predisposes to infections (reactivating TB)

anti-TNF antibodu

RA, psoriasis, AS

deposition of Ig at dermoepidermal junction

excess deposition of osteoid

mouth ulcers (stomatitis), hepatotoxivitu, pulmonary fibrosis, myelosuppression, B-cell lymphome

These are conditions asociated with defects in the oligiodendrocytes.

1. Acute inflammatory demyelinative diseases
i. MS--produces demyelinated plaques around the ventricles
2. Progressive multifocal leukoencephalopathy--an infectious disease of the CNS in which the polyoma JC virus infects and kills oligodendrocytes, resulting in fatal demyelination
3. Periventricular leukomalacia--softening of the white matter, usually around the ventricles. This condition is most often seen in premature infants, and produces regions of necrosis around the ventricles. It is the underlying pathology of most cases of cerebral palsy.
4. Leukodystrophy--destruction of the white matter due to biochemical abnormalities in myelin lipids and proteins

Limb paralysis
Hypertonia/spasticity
Hyper-reflexia
Disuse atrophy

(a) caused by transection of the corticospinal tract or destruction of the cortical cells of origin

CONTRALATERAL

Muscle paralysis
Hypotonia/atonia
Hyporeflexia
Wasting, fasisculations

IPSILATERAL

Poliomyelitis, Werdnig-Hoffman

Spatial neglect syndrome (agnosia of the contralateral side of the world)

Reduced levels of arousal and wakefulness (e.g. coma)

may result in tremor at rest, chorea, or athetosis

Intention tremor, limb ataxi

damage to the cerebellum results in ipsilaeral deficits; fall toward side of lesion (cerebellum --> SCP --> contralateral cortex --> corticospinal decussation = ipsilateral)

Truncal ataxia, dysarthria

Eyes look away from side of lesion

Eyes look toward lesion

contralateral hemiparesis (lower extremities)

medial lemniscus (decreased contralateral proprioception)

ipsilateral paralysis of hypoglossal nerve

= MEDIAL MEDULLARY SYNDROME (Anterior Spinal Artery)

1. Controlateral loss of pain and termperature
2. Ipsilateral dysphagia
3. Hoarseness *CN X, vagus problem*
4. decreased gag reflex
5. vertigo
6. diplopia
7. nystagmus
8. vomiting
9. ipsilateral Horner's
10. ipsilateral facial pain and temperature
11. trigeminal nucleus (spinal tract and nucleaus)
12. ipsilateral ataxia

= LATERAL MEDULLARY SYNDROME (PICA, Wallenberg's)

1. Ipsilateral facial paralysis
2. ipsilateral cochlear nucleus
3. vestibular (nystagmus)
4. ipsilateral pain and temperature
5. ipsilateral dystaxia (MCP, ICP)

contralateral homonymous hemianopia with macular sparing; supplies occipital cortex

contralateral face and arm paralysis and sensory loss, aphasia (dominant sphere), left-sided neglect

Supplies medial surface of brain, leg-foot area of motor and sensory cortices --> bilateral lower qquandrantanopia

Divisions of middle cerecral artyer; supply internal capsule, caudate, putamen, globus pallidus.

Arteries of stroke -- infarct of the posterior limb of the internal capsule causes pure motor hemiparesis

PML is a disease of the white matter in the brain that typically affects patients with T cell suppression (e.g. AIDS patients, cancer patients). Demyelination is caused by the JC virus, which triggers lysis of oligodendrocytes. Unlike MS, the spinal cord and optic nerve are spared.
In 1:1,000 cases, PML can be triggered by natalizumab therapy.
Symptoms of PML include:
Cognitive and personality disorder
Motor weakness
Seizures

On MRI, huge lesions will be visible in the white matter. The JC virus should be detectible in the CSF.

About 50% of patients with PML respond to highly active anti-retroviral therapy (HAART).

The average survival of patients with PML who do not have AIDS is about a year. The average survival of patients who do have AIDS is a few months.

progressive personality and cognitive changes, and may be misdiagnosed as schizophrenia or bipolar disorder. Patients may also experience seizures.
A diagnosis of metachromatic leukodystrophy can be confirmed with:
Deficient arylsulfatase A activity in the urine
Metachromatic granules on nerve biopsy
Symmetrical white matter lesions visible on MRI
Metachromatic leukodystrophy affects both the CNS and the PNS.

tan-grey lesions within the white matter. Plaques are of a firmer consistency than the surrounding white matter (hence, the name "sclerosis"), due to the inflammatory process, and are most commonly found-
Around the lateral ventricles
Optic nerve and chiasm
Brainstem tracts
Cerebellum
Spinal cord

The active phase—lesions are sharply defined with lots of inflammatory cells (typically, chronic inflammatory cells—lymphocytes and macrophages). Most inflammatory cells are found around the blood vessels and at the periphery of the plaque. In the lesions, axons are preserved, but the myelin is destroyed.

The inactive/gliotic phase—lesions have little myelin, reduced numbers of oligodendrocytes, and proliferation of astrocyte processes.

- Blindness/retrobulbar neuritis—caused by demyelination of the optic nerve. Unilateral visual loss with a dark, cloudy area in the center of the visual field ("central scotoma" is a common presenting symptom
- Motor weakness
- Cerebellar ataxia
- Depression
- Psychosis
- Parasthesia

(a) Proximal muscle weakness, sometimes with severe involvement of the extraocular muscles involved in eye movement
(b) weakness may be accompanied by other neurologic symptoms, lactic acidosis, cardiomyopathy
(c) ragged red fibers
(d) some contain paracrystalline parking lot inclusions

(a) Point mutation
(b) genes encoded by nuclear DNA
i. Leigh syndrome
ii. Barth syndrome
(c) deletions or duplications
i. Kearns-Sayre syndrome, which is characterized by ophthalmoplegia and pigmentary degeneration of the retina and complete heart block

(a) Sustained involuntary contraction of a group of muscles
(b) AD, presents late childhood with abnormailities in gait secondary to weakness of foot dorsiflexors and subsequently progresses to weakness of the hand intrinsic muscles and wrist extensors
(c) atrophy of muscles of face and ptosis ensue; cataracts
(d) can occur in ion channel myopathies along with hypotonicparalysis

Cingulate gyrus herniates under falx cerebri

anterior cerebral artery

medialprotion of temporal love herniates through the tentorium cerebelli

compression CN III, posterior cerebral artery (=hemorrhagc infarction of occipital lobe), parasympathetic fibers

Seen in elderly, due to neuronal loss = dilation of ventricles (no increase in pressure)

Triad --
1) dementia
2) apraxia (magnetic) gait
3) urinary incontinence

Freidrich's ataxia

ch 21
defective superoxide dismutase 1

see degeneration in UMN & LMN, common in cervical enlargment -- bilateral
1, progressive spinal muscular atrphy (ventral horn)
2. primary lateral sclerosis (corticospinal tract)
- spastic paralysis in lower limbs
- flaccid paralysis in upper limbs
- increased tone and reflexes

Riluzole (glutamate antagonist)

confusion
atacia
nystagmus
opthalmoplegia

antero/retrograde amneia
confabulations
hallucinations

Malignant smell cell tumor, primarily in children -- orimnitive neuroectodermal tumor; sheets of small cells, mitotic figures

Arises from the external granular cell layer of the cerebellum, often located in the cerebellar vermis

Often seeds the neuraxis and invades the fourth ventricle

chr. 20, a helix --> b-pleated PrP

1. thrombis (pale infarct) -- due to atherosclerosis

2. embolus (usually from heart) -- think of a fib, infective endocarditis

3. hyaline arteriosclerosis -- small vessel disease affecting basal ganglia, brainstem

epidural
middle meningeal
CN III palsy
lenticular appearance
can have subfalcine herniation

subdural
bridging veins )low pressure)
develops over time
crescent shape on CT
impairmen of cognitive skills, gait instability days, week later

damages anterior white comminsure of spinothalamic tract, resulting in bilateral loss of pain and temperature
- cape-like distribution (C7-T1)
- bladder problems, charcot arthropathy

- sudden loss of vision
- nystagmus in abducting eye
- hemiparesis
- incontinence
- scanning speech
- intention tremor

Lewy Bodies -- intracytoplasmic round eosinophilic inclusions that contain a-synuclein

Alzheimer's is global, while Pick's locally affects anterior or tempral lobe.

Alz's atrphy more pronouned in frontal love and hippocampus

- neurofibrillary filament (made of TAU); aggregates of insoluble cytoskeletal elements

- Hirano bodies (Small,round eosinophilic lesions)

- amyloid (seen in neuritic plaques and blood vesels)

- graunulovaculoar degeneration

involves limbic system, cingulate gyrus
Parkinson's + hallucination + memory loss

Staggering gait
frequent falling
nystagmus
dysarthria
pes cavus
hammer toes
hypertropic cardiomyopathy (death)

presents in childhood with kyphoscoliosis

no sensory deficits

autosomal dominant defect in porphyrin metabolism w/deficient uroporphyroginogen synthase
- porphorbilinogen and aminolevulinic acid increase
- urine initially colorless, turns dark red on light
- may develop severe ab pain, psychosis, neuropathy, dementia

illusion of movement, not to be confused with dizziness or lightheadedness.

peripheral vertigo -- more common. inner ear etiology (e.g. semicircular canal debris, vestibular nerve infection, Meniere's disease). Positional testing --> delayed horizontal nystagmus

Central vertigo -- brain stemor cerebellar lesion (e.g. vestibular nuclei, posterior fossa tumor). Positional testing --> immediate nystagmus in any direction; may change directions

1. ipsilateral dilated pupil/ptosis -- stretching of CN III (innervates levator palpebrae)

2. contralateral homonymous hemianopia -- compression ipsilateral posterior cerebral artery

3. ipsilateral paresis -- compression of contralateral crus cerebri (Kernohan's notch)

4. duret hemorrhages -- paramedian artery rupture -- caudal displacement of brain stem

1. proenceph
2. mesenceoh
3. rhomboenceph

Pros --> tel, di
Telencephalon wall -- cerebral hemispheres
Telencephalon cavity -- lateral ventricles
Diencephalon wall -- thamus
Diencephaon cavity -- 3rd ventricle

Mes --> mes
Mesencephalon wall -- midbrain
Mesenecephalon cavity -- aqueduct

rhombo --> met, myel
Metenceph wall -- pons, cerebellum
Metenceph cavity -- 4th ventricle

Myenceph wall -- medulla
Myenceph cavity -- 4th ventricle

perinatal brain injury --

germinal matrix hemorrhage
periventricular leukomalacia (infarcts in watershed areas)
multicystic encephalopathy (multiple brain infarcts occur early in pregnancy)

1. stimulus

2. 1st order
- receive signal, send message to CNS, located in dorsal root or spinal cord ganglia

3. 2nd order
- signal receives (in spinal cord or brainstem) in relay, sends to thalamus; may cross midline

4. 3rd order
- located in thalamus, send to cerebral cortex

5. 4th order = conscious perception

First Order
- signal in doral root --> ipsilateral nucleus gracilis/cuneatus of medulla

Second Order
crosses midline, ascends to contralateral thalamus (VPL -- body sensation)

Third Order
- ascends to sensory cortex

First Order
- stimulus from A-d and C fibers enter spinal cord at dorsal horn

Second Order
- crosses midline (almost immediately) --> anterolateral quandrant of spinal cord --> ascend to contralateral thalamus (VPL)

Third Order
- ascend to somatosensory cortex

A lesion to the thalamic nuclei results in loss of sensation of contralateral side of body

VA -- motor
VL -- body sensation
VPL -- spinothalamic/dorsal
VPM -- trigeminal and gustatory pathway (face sensation and taste)

LGN -- input CN II, sense to calcarine sulcus
MGN -- input superior olive and inferior collicular of pons, sens to auditory cortex of temporal lobe

rods -- sensitive to low light, lower visual acuity not in fovea, rods adapt later, no color vision

cones -- sensitive to high intensity light, increased acuity in fovea, adapt first, color vision

partial agonist at opiod mu receptors, agonist at kappa

pain, causes less resp depression that full agonists

causes withdrawal if on full opioid agonist

very weak opoid agonists, also inhibits serotonin and NE reuptake (works on multiple transmitters)

chronic pain

similar to opioids, decreases seizure threshold

phenytoin, carbamepazine, valproic acid

NO (>100%)

Halothane (0.75%)

Increased cerebral vascular flow and intracranial pressure

increased blood solubility, which increases gas required to saturate blood = slower onset of action (samd as in tissue)

nephro -- methoxyflurane

proconvulsant -- enflurane

loperamide
diphenoxylate

for Alzheimers
cholinesterase inhibitor
hepatotoxic

treatment of COPD, asthma

at low doses, prevent binding of Ach, prevent depolarization of muscle cell membrane, inhibit muscle contraation, compete with ACh

at high doses, blocks end plate

releases histamine = fall in BP, flushing, bronchoconstriction

depolarizing

lasts several minutes, used for intubation
hyperthermia, apnea (paralysis of diaphragm), hyperkalemia

Blocks relrease of NE

Relative of two or more agonists to produce same magnitude of effect, shown by proximity of cruve to y axis (if curves do not rss)

How well drug produces response, shown by max height reached by curve

decreased synthesis of gonadotropin in the anterior pituitary; anosmia, lack of secondary sexual characteristics

involves a generalized arteriolar constriction that impacts the brain (seizures and stroke), kidneys (oliguria and renal failure), liver (edema), and small blood vessels (thrombocytopenia and DIC).

(a) Preeclampsia – hypertension, edema, proteinuria
(b) Eclampsia – + seizures

1. 1st weeks – low progesterone levels (no response to beta-hCG)
2. 1st trimester – chromosomal abnormalities (e.g. robertsian translocation)
3. 2nd trimester – bicornate uterus (incomplete fusion of paramesonephric ducts)

Distention of unruptured graafian follipcle. May be a/w hyperestrinism and endometrial hyperplasia. Regress spontaneously.

Most common ovarian mass in pregnancy. Hemorrhage into persistent corpus luteum. Commonly regresses spontaneously.

Often bilateral/multiple. Due to gonadotropin stimulation. A/w choriocarcinoma and moles -- has to do with b-hCG; related to pregnancy

Blood-containing cyst from ovarian endometriosis. Varies with menstrual cycle.

Teratoma that contains functional thyroid tissue. Can present as hyperthyroidism.

Malignant. Pseydomyxoma peritonei -- intraperitoneal accumulation of mucinous material from ovarian or appendiceal tumor.

Rhabdosarcoma variant that affects young girls (<4) with spindle-shaped tumor cells that are desmin positive.
Poor prognosis.

cyst of lateral duct due to persistence of mesonephric ducts

absence of upper part of vagina and uterus, presents with primary amenorrhea

Orderly row of cells "single file"
Often multiple, bilateral
There is about a 20% chance that the opposite breast will also be involved, and many of them arise multicentrically in the same breast.
5%

Loss of e-cadherin cell adhesion gene on chrom 16
can also present with signet ring cells

fleshy, cellular, lymphocytic infiltrate. good prognosis

Malignant, painless. homogenous testiular enlargment; most common testicular tumow, mostly affecing males age 15-35. large cells in lobules with water cytoplasm and a "fried egg" appearance. Radio & chemo sensitive. Late mets, excellent prog. Note the lymphoid stroma between the nests of seminoma.

malginant, painful, worse prognosis than seminoma. Often glandular/papillary morphology. Sheets of blue cells are trying to form primitive tubules. Can differentiate to other tumors. May be a/w AFP, b-hcg

Contains Reinke crystals. usually androgen producing; gynecomastia in men, precocious puberty in boys. Golden brown color.

androblastoma from sex cord stroma

most common testicular cancer in older men

Lestions in ther serous covering of testis -- present as testicular masses that can be transilluminated (vs. testicular tumors)
1. varicocele -- dilated vein in pampiniform plexusl can cause infertility, "bag of worms"; usually seen on left testicle due to either increased venous pressure (drains to left renal vein) or obstruction (renal cell carcinoma)
2. hydrocele -- increase seconarty to incomplete fusion of the processus vaginalis; invariably a/w indirect inguinal hernia. painless.
3. spermatocele -- dilated epididymal duct containing sperm

Gray, solitary, crusty plauw usually on the shaft of the penis or on the scrotum; peak incidence in the 5th decade of life; progresses to invasive SCC in < 10% of cases.

Red velvety plaques, usually involving the glansl for of Bowen's disease?

Multiple papular lesions; affects younger age group than other subtypesl usually does not become invasive

Causes masculinization in females; reduces intratesticular testosterone in males by inhibiting release of LF (via neg feedback), leading to gondal atrophy.
Premature closure of epiphyseal plates. Increased LDL, decreased HDL.

A nonsteroidal comp. inhibitor of androgens at the testosterone receptor. Used in prostate carcinoma.

Keto -- inhibits steroid synthesis (inhibits desmolase)

Spir -- inhibits steroid binding

Both are used in the treatment of polycystic ovarian syndrome to prevent hirutism. Both have side effects of gynecomastia and amenorrhea

partial agonist at estrogen receptors in hypothalamus. Prevents normal feedback inhibition and increased release of LH and FSH from pituitary, which stimulates ovulation. Used to treat infertility and PCOS. May cause hot fflashes, ovarian enlargement, multiple simulataneous pregnancies, and visual disturbances

aromatase inhibitors used in postmenospausal women with breast cancer.

PGE2 analog causing cervical dilation and uterine contraction, inducing labor

b2-agonist that relax the uuterus; reduce premature uterine contractions. Ritodrine allows the fetus to :return to dreams: by preventing early delivery.

a1-antagonsit used to treat BPH by inhibiting smooth muscle contraction. Selective for a1ad receptors (found on prostate) vs vascular a1b receptors.

headache, flushing, dyspepsia, impaired blue-green color vision. Risk of life-threatening hypotension in patients taking nitrates.

Acute -- group B strep, group A, staph aureus, bacteriodes fragilis, clamydia, gonorrheae, e.coli

Chronic -- IUD w/actinomyces, gonorrhea

benign tumor a/w Meig's Syndrome (ascites, right-sided pleural effusion); regression of effusions follows removal of tumor.

he thecoma component of the neoplasm gives the tumor a yellowish cast because of the lipid content and can also produce estrogen. These are tumors that arise from the ovarian stroma. They are bilateral in only about 10% of cases. A right-sided hydrothorax in association with this tumor is known as Meig's syndrome.

Penis
Prostate
Scrotum

benign tumor of the modified appocrine sweat glands of labia majora and interlabial folds; may mimic carcinoma (ulceration and along milk line)

contains both malignany stromal cells and endometrial adenocarcinoma.

develops into female internal --
fallopian tube
uterus
upper 1/3 of vagina
(lower 2/3 from urogenital sinus)

ascending STD infection from cervix to endometrium to fallopian tubes to pelvic cavity.

1. vaginal discharge (cervicitis)
2. vaginal bleeding and midline ab pain (endometriosis)
3. bilateral lower ab and pelvic pain (salpingitis)
4. abdominal tenderness and peritoneal signs (guarding, etc) (peritonitis)
5. Fitz-Hugh-Curtis Syndrome --pain localizes to pleuritic right

1. salpingitis can get called off = abscess (tubo ovarian)
2. healing leads to scarring --> infertility, ectopic pregnancies
3. fibrous adhesions ("violin strings") --> intestinal obstruction

isochromes occur when the centromere divides transversely (instead of longitudinally) so that one of the chromosome arms is duplicated and the other arm is lost.

Isochrome Xq is found in 20% of Turner's.

1. b/c spreads hematogenously -- spread to lungs

2. b-hCG --> gynecomastia

gram neg that causes chancrinoid
male dominant
high incidence of HIV
painful genital and perianal ulcers with suppurative inguinal nodes
Diagnosis with Gram stain ("school of fish") appearance

treat with ceftriazone or azithromycin

Dysgenesis of seminiferous tubuls --> decreased inhibit, which increases FSH

Abnormal Leydig cell function --> decreased testosterone --> increased LH and estrogen

obturator, external iliac, hypogastric

(a) Suspensory ligament of the ovaries – connects ovaries to the lateral pelvic wall (contains ovarian vessels)
(b) Cardinal ligament – cervix to side wall of pelvis (contains uterine vessels)
(c) Round ligament of the uterus – uterine fundus to labia majora
(d) Broad ligament – uterus, fallopian tubes, and ovaries to pelvic side wall (ovariaes, fallopian tubes, and round ligaments of the uterus
(e) Ligament of the ovary – ovary to lateral uterus

1. pulsatile release of GnRH
2. FSH and LH stimulated
3. FSH stimulates aromatase, which turns androsenedione into estrogen in the granulosa cell
4. LH stimulates desmolase (17a-hydroxylase), which turns cholesterol into androstenedione in theca cell

increase transport of proteins
SHBG
increase HDL, decrease LDl

stimulation of prolactin secretion, but blocks its action at the breast

1. stimulation of endometrial glandular secretions and spiral artery development
2. maintainance of pregnancy
3. degcreased myometrial excitability
4. production of thich cervical muscus, which inhibits sperm entry into uterus
5. inceased body tempeature
6. inhibition of gonado
7. uterine smooth relaxation (preventing contractions)
8. decreased estrogen receptor expressivity

FSH --> follicle maturation --> production of estradiol --> production of LH surge --> ovulation and production of progesterone (along with estradiol) --> inhibition of FSH and LH production --> decline of corpus luteum --> no production of estradiol and progesterone --> loss of FSH inhibition --> increase in FSH

> 35 days

< 21 days

frequent but irregular menstruation

heavy, irregular menstruation at irregular intervals

arcute nucleus

Basalis
Spongiosum (shed)
Compactum (shed)

produces progesterone until the placenta can form and take over with b-hCG

inhibits antithrombin III, increases the synthesis of fibrinogen, V, VIII

PCOS
obesity
HPO axis abnormalities
premature ovarian failure
hyperprolactinemia
thryoid disorder
eating disorders
Cushing's syndrome
adrenal insufficiency

endometrial cancer

increased risk in PCOS b/c of constant stimulation of the uterus

1. LH is increased and stimulates production of androgens in the theca cells
2. estrodione is being made in the fat cells, leading to increased estrogen and positive feedback on LH
3. FSH will be suppressed

1. CO increases 30-50%
2. plasma volume increases 50%, RBC volume increases 30%
3. BP decreases in early pregnancy
4. mild resp alkalosis
5. increased procoagulation factors
6. normal TSH and free T4
7. increased peripheral resistance to insulin that worsens through pregnancy --> hyperinsulinemia, hyperglycemia, hyperlipidema

accreta
previa

may have signet ring cells
always estrogen, progesterone positive

muscle spindle

golgi tendon

Ventral tegmental of midbrain --> cotex

Increase in negative symptoms of psychosis (ie social withdrawal and depression)

Ventral tegmental of midbrain --> limbic

Relief of psychosis (positive symptoms)

substantia nigra (pars compacta) --> striatum (caudate + putamen)

Parkinson's symptoms (stimulation would result in extrapyramidal side effects)

Arcute nucleus of hypothalamus --> pituitary (to inhibit prolactin)

Increase in release of prolactin from pituitary --> amenorrhea, gynecomastia, galactorrhea

Postural instability
slurring of speech

anterior governs legs: broad based, staggering gait
chromic alcohol abuse = thiamine deficiency = degeneration of the cerebellar cortex

Essential -- family history of tremor, occurs with movement and rest

Resting -- a/w Parkinson's disease, disappears with voluntary movement

Intention tremor -- a/w cerebellar damage, appears only with voluntary movement

inability to express emotion or inflection in speech

inability to comprehend emotion of infection in speech

posterior communicating artery lesion

anterior communicating artery lesion

midbrain infarction resulting from occlusion of the paramedian branches of posterior cerebral artery (Weber's)

2-3 days after, risk of vasospasm due to blood breakdown products, which irritate vessels (use Ca channel blackers like nimodipine to treat)

rapid expansion under systemic arterial pressure --> transtentorial herniation

CN III palsy

Caused by hypertension, amyloid angiopathy -- lobar strokes all over brain, DM, and tumor. Typically occurs in basal ganglia and interal capsule.

Severe headache, nausea, vomitting; steady progression 15-20 minutes --> coma

hemorrhage into ventricular system
most common in premies within first 72 hours.

originates from the germinal matrix in the subependymal, subventricular zone that gives rise to neurons and glia during development

hippocampus
neocortex
cerebellum
watershed

Lateral, 3rd, 4th vent

CSF made by choroid plexus, reabsorbed by venous sinus arachnoid granulations

superior sagittal sinus main location of CSF return via arachnoid granulations

decreased CSF absorption by arachnoid villi, which can lead to increased intracranial pressure, papilledema, and herniation (e.g. arachnoid scarring post-meningitis)

young, obese female
headache -- daily (wose in the morning), pulsatile, possible nausea/vomiting, possible retrocular pain worsed by eye movement

papiledema, vision loss
abence of ventricular dilation, no tumor or mass
CSF pressure elevated (>200mmHg in nonobense, >250mmHg in obese)

1. medulla
2. medullary pyramid
3. anterior white commisure

Problems with 6 & 7

lesion in the pons

located in tegmentum portion of brain stem (b/w dorsal and ventral positions)

1. midbrain -- 3, 4
2. pons -- 5,6,7,8
3. medulla -- 9,10,11,12

since th soft palate fibers from the right motor cortex (or right corticobulbar tract) travel to the left nucleus ambiguus, the uvula will deviate to the right (towards the side of the lesion)

nucleus ambiguus -- motor innervation of pharynx, larynx, and upper esophagus (8,9,10)

FACIAL

TRIGEMINAL

axillary nerve (teres minor)

Peroneal prob -- sensory anterolateral leg and dorsal aspect of foot

motor -- foot eversion and toe extension (foot is DROPPED)

common peroneal

No constriction of either the left or right eye when light is shined in eye
Both pupils constrict if the light is shined in the left eye

Right eye will not respond to light shone in either the left or right eye

left eye will constrict when a light in shined in either eye

afferent defect

my Lovely Bell Has An STD

Lyme disease
Herpes Zoster
AIDS
Sarcoidosis
Tumors
Diabetes

center -- output to ocular muscles: affected primarily by vascular disease (e.g. diabetes: glucose --> sorbitol) due to decreased diffusion to interior

Outer -- parasympathetic: affected 1st by compression (e.g. PCA berry aneurysm, uncal herniation); use pupillary light reflex in assessment)

separation of neurosensory layer of retina from pigment epithelium --> degeneration of photoreceptors --> vision loss. May be seconary to trauma, diabetes

Degeneration of macula (central area of retina). Causes loss of central vision (scotomas).

Dry/atrophic ARMD is slow, due to fat deposits and causes gradual decrease in vision.

"Wet" ARMD is rapid, due to neovascularization

dementia
aphasia
parkinsonian aspects
spares parietal lobe and posterior 2/3 of superior temporal gyrus

Parkinsonism with dementia and visual hallucination

may be a/w partial Horner's syndrome (ptosis and miosis), ipsilateral nasal congestion or eye rednress, rhinnorhea or tearing

MS

Meniere

disorder of the inner ear that can affect hearing and balance to a varying degree. It is characterized by episodes of vertigo and tinnitus and progressive hearing loss, usually in one ear.

MS

Meniere

disorder of the inner ear that can affect hearing and balance to a varying degree. It is characterized by episodes of vertigo and tinnitus and progressive hearing loss, usually in one ear.

pheny
carb
valp

diplopia
sedation
ataxia
nysatgmus
dizziness

gingerval hyperplasia
SLE
hirutism
increased 450
megaloblastic anemia

valp
carb

phen
cab
val
lamotrigine
topiramate

top
valp
benzo
phenobarbitol

small-diameter fibers > large diameter.

myelinated > myelinated.

Overall, size factor predominates over myelination such that small unmyelinated > small unmy > large my > large unmy

pain
temp
touch
pressure

With vasoconstrictors (usually epinephrine) to enhance local action

decrease blooeding
increases anesthesia by decreasing systemic concentration

B12 and folate

(methionine turned into homocysteine, using homocysteine methyltransferase)

von Gierke (type I -- glucose 6 phosphatase deficiency)

No gluconeogenesis

Pompe's (II)

Cori (III)

less severe form of Von Gierke (type I) b/c CAN breakdown glycogen but not fully

Pompe

Cori

arsenic inhibits lipoic acod

Findings: vomiting, rice water stools, garlic breath

3 NADH
1 FADH2
2 CO2
12 ATP

x 2 per glucose

Occurs in mitochondria

amytal (barbituate)
rotenone (fish protein)
MPP

antimycin A

1. ATP
2. NADH, NADPH, FADH2
3. CoA, lipoamide
4. biotin
5. THF
6. SAM
7. TPP

3 NADH
1 FADH2
2CO2
12 ATP

x 2 per glucose, in mitochondria

lactating mammary glands, liver, adrenal cortex (sites of fa OR STEROID SYNTHESIS), rbcS, NEUTROPHILS

free radicals generated via inflammatory response can diffuse into RBCs and cause oxidative damage

OAA is depleted for gluconeogensis, which stalls the TCA cycle, which shunts glucose and FFA toward production of ketone bodies

NADH shunts OAA to malate, which stalls the TCA cycle, which shunts glucose and FFA toward production of ketone bodies

Produced:
glucose from liver
FA from adipose

Used -- muscle, brain, and others predom use glucose

Begins 4-6 hours after last meal
Fully active when glycogen stores are depleted (10-18 hours after last meal)

Produced:
Glucose from gluconeogenesis w/some glycogen from glycogenolysis
FA from adipose tissue

Used:
brain predouse glucose
muscles and other tissues use some glucose but predom fatty acids

Produced:
glucose from gluconeogenesis, no more glycogenolysis
FA
ketones from liver

Used:
brain predom uses glucose but also some ketones
muscles and other tissues use predom FA but also some ketones

excess acetyl CoA from FA synth

RBCs cannot use ketones

Prod:
glucose
FA
keto

Used:
brain predom use ketones
muscles and other tissues predom use FA but also some ketones

overnight:
95% glucose (2/3 glycogen breakdown, 1/3 gluconeogenesis)
5% from ketone bodies

3 day:
60% from ketone bodies (1/2 b-hydroxybutyrate, 1/2 acetoacetate)
40% from glucose (most from gluconeogenesis)

PCA

1. Peripheral Chemoreceptors

2. Central Chemoreceptors

Receptors located on medulla.
Assess PaCO2 and H+ -- normal regulation

Cause hyperventilation in response to low pH in the CSF, hypoventilation when high pH in CSF. (e.g. meningitis will lead to increased H+ in CSF)

These receptors are located in the carotid bodies (at bifurcation of common carotid) and aortic bodies (above & below aortic arch).

The following will produce an increase in breathing rate:
Decrease in PO2 (<80) -- response occurs when PO2 reaches below 60 mmHg (breathing rate will increase steeply and linearly).

will take over breathing drive, so for one who has chronically hypoventilated, the peripheral receptors dominate so don't correct PaO2 b/c lose drive to breathe

Lungs want to collapse inward (lung recoil, positive pressure)

Chest wall wants to spring outward (intrapleural pressure, negative pressure)

PVR = P(pulm artery) - P(LA wedge pressure) over CO

alveloar PO2 = inspired PO2 - (arterial PCO2/R)

can be apprx
alveolar PO2 = 150 - (arterial PCO2/0.8)

with exercise (increased CO), there is vasodilation of apical capillaries, resulting in V/Q ratio that approaches 1.

1. Bicarbonate
2. bound to hemoglobin at N terminus of globin (not heme( as carbaminohemoglobin
3. dissolved

Cl influx for HCO3- outflux
Hypochloremia = impaired efflux --> acidosis b/c backup of CO2 in RBCs

1. Kidney Cell will produce erythropoeitin, which acts on bone marrow to stimulate RBC production.

2. Vascular muscle cells will constrict.

In lungs, oxygenation of Hb promotes dissociation of H_ from Hb. This shifts equilibrium toward CO2 formation; therefore, CO2 is released from RBCs.

In peripheral tissue, increased H+ from tissue metabolism shifts curve to right, unloading O2 (Bohr effect)

All the intercostal muscles are innervated by the corresponding spinal cord segment.
The diaphragm is innervated by C3-5.
Spinal cord damage at the low cervical levels will lead to paralysis of the intercostal muscles. Spinal cord damage at the high cervical level will lead to paralysis of the diaphragm, impairing the ability of the patient to breath independently.

change in lung volume for a given change in pressure; decreased in pulmonary fibrosis, insufficient surfactant, and pulmonary edema.

Specific compliance (not affected by changing volume).

Elastic pushes lungs in.

Chest wall tries to expand outward.

Alveoli at top of lungs = lower pressures and larger than alveoli at the bottom of the lungs. (weight of the lungs presses on bottom alveoli, which creates a positive pressure that counters the negative pressure created by the pleural space)

R=8nl/πr4
-n = coefficient of the gas's viscosity
-l = length of the airway
-r = radius of the airway

At least 70% of the lung volume should be able to be exhaled in a second. Therefore, FEV1/FVC should be 70% or higher. If it is less than 70%, there is respiratory obstruction.

The rate of CO2 production/rate of O2 consumption. On average, less than one, but depends on substrate.

pseudostratified ciliated columnbar cells extend to the respiratory bronchioles (macrophages clear debris in alveoli)

goblet cells extend only to bronchi

Oxidized form of Hg that does not bind O2 as readily, but has increased affinity for Cn.

To treat Cn poisoning, use nitrites to oxidize Hg to metHg, which binds cyanide, allowing cytochrome oxidase to function. Use thiosulfate to bind this cyanids, forming thiocyanate, which is renally excreted

chloroquine, primaquine
dapsone
sulfonamides
local anesthetics
metoclopramide
nitrates

hypochromic microcytic anemia

no change in O2 delivery or O2 saturation, but not as much hemoglobin (diffusion limited)

CHF -- lungs not perfused well enough to oxygenate the rest of the body

1. COPD (destruction of lung parenchyma)
2. emboli (decreased cross sec area)
3. mitral stenosis (increased resistance, LHF)
4. shunting disease (increased shear stress)
5. sleep apnea or high alt (hypoxic vasoconstric)
6. autoimmune disease

due to an inactivating mutation in the BMPR2 gene (normally functions to inhibit vascular SM prolferation)

poor prognosis

a/w HIV and Kapso sarcome

severe respiratory distress --> cynanosis and RVH --> death from decompensated cor pulmonale

Bosentan -- competivitely inhibt endothelin-1 receptors, decreaing pulmonary vascular resistance

Prosta
Sildenafil
Nifedipine

300 - 500 mmHg normal
< 300 mmHg --> gas exchange deficit
< 200 mmHg --> severe hypoxia (ARDS)

1. apex -- 3 (wasted vetilation)
2, base -- 0.6 (wasted perfusion)

serous cystadenoma

gallstones
alcohol

alsochol (adults)
CF (kids)

Turner

chronic hepatitis
cirrhosis
hemochromatosis
a-1 antitrypsin

Pericarditis
Cor tamponade
Asthma
Sleep apnea
Croup

Drugs
Neoplasm
Allergy, Asthma
Addison's
Acute interstitial nephritis
Collagen vascular disease
Parasites

Shock, infection, toxic gas inhalation, aspiration, high O2, pancreatitis, herioin leads to INFLAMMATION and FREE RADICALS

damage to endothelial or alveolar epithlial Type I cells

diffuse alveolar damage and hyaline membrane disease

Absent/decreased breath sounds
decreased resonance
decreased fremitus
deviation tward side of lesion

decreased breath sounds
dullness
decreased fremitus, no tracheal dev

may have bronchial breath sounds over lesion
dullness
increased fremitus
no trach deviation

decreased breath sounds
hyperresonant
absent fremitus
trach dev away from lesion

squamous cell
bronchogenic carcinoma
mesothelioma

h. influ

cystinuria

use acetazolamide to alkanize urine, prevent stones

fructose intolerance

pyruvate dehydrogenase def

Causes backup of substrate (pyruvate and alanine), resulting in lactic acidosis. Can be congential or acquired (B1 def in alcoholics)

to the right shoulder via phrenic nerve

fat
female
fertile
fourty
native american
cf
crohn's disease
fibrates
rapid weight loss

chromic hemolysis
alcoholic cirrhosis
age
biliary infection

7a hydroxylase

7a hydroxylase

Lesch Nyhan
G6PD deficiency
OTC deficiency

Lesch Nyhan
G6PD deficiency
OTC deficiency

In bowel, becomes acidic --> traps ammonia and additionally, pulls from blood = excreted

In bowel, becomes acidic --> traps ammonia and additionally, pulls from blood = excreted

inhibits LPL

inhibits LPL

binds to cyclophilins. blocks the differentation and activation og T cells by inhibiting calcineurin, thus preventing the production of IL-2 and its receptor.

Predisp patients to viral infections and lymphoma; nephrotox (preventab;e with mannitol diuresis

similar to cyclosporine; binds to FK-binding protein, inhibiting secretion of IL-2 and other cytokines

Tox -- nephrotox, peripheral neurop, hypertension, pleural effusion, hyperglycemia

binds FKBP-12 intracellular protin --> inhibition of mTOR --> inhibition of T cell prolif

Immunosupression after kidney transpplant with cyclosporine and corticosteroid

monoclonl antobody with high affinity got IL-2

monoclonal antibody that binds CD on the surface of T cells. Blocks cellular interaction with CD protein responsible for T cells signal transduction.

tox -- cytokine release syndrome hypersensitive reaction

cyclosporine

daclizumab

mycophenylate

tacrolimus

Sirolimus

pre: 120-139/80-89

hyper 140/90

Staph areus
Viridans
Entero (VRE)
Epidermidis

Haem
Actinobacillus
Cardiobacterium
Eichenella
Kingella

ear
olacrenon bursa
big toe

Duodenum
Descending colon (right side)
Ascending colon (left side)
Kidneys and ureters
Pancreas
Aorta
IVC
adrenals & rectum

connects liver to anterior abdominal wall

contains ligamentum teres

derived from fetal umbilical vein

connects liver to anterior abdominal wall

contains ligamentum teres

derived from fetal umbilical vein

Liver to duodenum

contains portal triad" hepatic artery, portal vein, common bile duct

Liver to duodenum

contains portal triad" hepatic artery, portal vein, common bile duct

Connescts liver to lesser curvature to csomach

contains gastric arteries

Connescts liver to lesser curvature to csomach

contains gastric arteries

connects greature cirvature and transverse colon
-- part of the greater omentum
contains gastroepilopic arteries