UWorld first half Flashcards
Dynein vs Kinesin
- Dynein is RETROGRADE transport down an axon (would be used to establish latent infection of HSV)
- Kinesin is ANTEROGRADE transport down an axon (would be used to RE-activate HSV from cell nucleus down to skin, if HSV-1, would be trigeminal, if HSV2 would be from sacral ganglion, if VZV would be from DRG)
These are receptors for what viruses?
- Cellular Integrin
- CR2 (CD21)
- CD4 and CXCR4/CCR5
- Nicotinic ACh Receptor
- ICAM 1 (CD54)
- Cellular Integrin –> Cytomegalovirus
- CR2 (CD21) –> EBV
- CD4 and CXCR4/CCR5 –> HIV
- Nicotinic ACh Receptor –> Rabies
- ICAM 1 (CD54) –> Rhinovirus (think photos of rhino)
Scapular Winging
Lesion of LONG THORACIC nerve usually seen after masectomy, axillary node dissection and stab wounds.
-Defect in SERRATUS ANTERIOR (abducts arm above horizontal plane)
Calculating Number Needed to Harm (NNH)
1/Attribuatable Risk
Calculate attributable risk: take the adverse pts/total pts for both treatment and placebo. Then take the difference of these two numbers and take 1/AR
Ex: 60/80=.75 (75%) and 38/76 =.5 (50%) then take the difference of these two .75-.5=.25. Then take 1 over this number 1/.25 =4
Trigeminal Neuralgia (tic douloureux)
Sudden severe pain the distribution of CN V that can be brought on by chewing or brushing teeth. Unknown etiology
Tx: Carbamezapine: inhibits neuronal high frequency firing (a drug used for simple, complex, and tonic clonic seizures)
Baclofen and Valproic Acid can be used but are not first line
JVD wave
A. Right atrial contraction
C. bulging of R tricuspid valve during ventrical contraction
X: R atrial relaxation
V: continued inflow of venous blood
Y: passive emptying of R atrium after tricuspid opens
DNA Polymerase I vs III
DNA Polymerase I: Degrades RNA primer, replaces it with DNA
DNA Polymerase III: elongates DNA strand by adding deoxynucleotides to 3’ end. Elongates lagging strand and proofreads. Replicates the E. Coli chromosome
“333 for eeeecoli”
Immediate vs Long-term treatment for Panic Disorder
Acute: Benzodiazapines are OK for acute relief but should not be used long term due to risk of abuse. Contraindicated if have a hx of any sort of substance abuse
Chronic: SSRI/SNRI/CBT because of the relative benign side effect profile
Primase
-Makes an RNA primer on whiche DNA Polymerase III can initiate replication
*Keep in mind Uracil is ONLY found on RNA so if it were present, know we must be talking a bout RNA and thus primase would be involved
-Primase is crucial for bacterial replication as DNA polymerase CANNOT initiate DNA synthesis without it
Staphalococcal Scalded Skin Syndrome
-Caused by exotoxin mediated skin damage (exofoliatin exotoxin)
Presents with + Nokolsky sign, epidermal necrolysis, fever, pain
-Most common in infants and young children
S1 nerve root impingement
- sensory loss of buttox, posterior thigh and calf, and lateral foot
- weakness in hip extension (glut maximus), ACHILLES reflex, foot plantarflexion (gastroc), knee flexion (hamstrings)
L4 nerve root compression
- sensory loss over lower anteriomedial thigh
- weakness hip adduction, knee extension (quads), PATELLAR reflex
Loss of patellar reflex is compression at ___, loss of achilles reflex is compression at ___
Patellar –> L4
Achilles –> S1
“one/two, tie my shoe, three/four kick the door, five/six pick up sticks seven/eight shut the gate
Bacterial pneumonia AFTER infleunza infection is typically what bacteria
S. Aureus
CAAT box
highly conseved sequence that serves as a promoter of transcription in the eukaryotic genome
Chlorthalidone
- potent thiazide diuretic (inhibit Na/Cl cotransporter in DCT)
- results in hypokalemia and metabolic acidosis (via activation of the RAAS system and losing of K)
Hypokalemia can cause muscle weakness, cramps, rhabdomyolysis
involuntary head bobbing
-usually caused by aortic regurgitation which results in a widened pulse pressure (peak systolic - end diastolic)
DIC in pregnancy
- mediated by release of tissue factor (thromboplastin) from sites of placental injury, which initiates the clotting cascade. Clotting factors are used up and this results in profound bleeding
- An abruption that leads to fetal demise is the most common cause of DIC in pregancy
pt presents with acanthosis nigricans what is the most likely diagnosis and what is elevated in serum
- Type II DM
- Free fatty acids are elevated in serum
insulin resistance in adipose cells hinders antilipolytic effects of insulin and therefore lipolysis takes place and an increase in free fatty acid is observed. This contributes to the insulin resistance by impairing insulin-dependent glucose uptake and increasing hepatic gluconeogenesis
overdose of Beta-blocker medications
- Presents as hypotensive and bradycardic on physcial exam (due to non-selective blockage of peripheral beta adrenergic receptors causing depression of myocardial contractility, bradycardia, and varying degrees of AV block)
- Tx with glucagon (increases cAMPm which increases intracellular Ca release leading to an increase in heart rate and cardiac contractility)
Colchicine mechanism
- primarily it works by inhibiting microtubular polymerization (cannot form microtubules)
- Also reduces the formation of Leukotriene B4
Adverse effects: nausea, diarrhea, abd pain
Atropine OD signs and symptoms and treatment
- restlessness, disoriented, combative
- peripherally can cause dry skin, hyperthermia, mydriasis, constipation (cant see, cant see, cant spit, cant shit)
Tx overdose with phyostigmine (not neostigmine because does not cross BBB into CNS due to quaternary structure)
Interscalene nerve block
- used for procedures involving the neck and upper arm. Good way to access the brachial plexus roots and trunks
- Causes transient IPSILATERAL DIAPHRAGMATIC PARALYSIS by anesthesizing the phrenic nerve root C3-C5
Rare but serious side effect of Trazodone
- Priaprism
- can also cause sedation, nausea, postural hypotension (remember blocks 5HT2 and A1 adrenergic
Temporary local hyperoxia (like seen in a premature infant given high doses of O2) results in what?
-Can induce VEGF in the retina resulting in neovascularizaion
=retinopathy of prematurity
What would be the use in these measurements?
- aPTT
- PT
- Bleeding time
- Fibrinogen Levels
- Fibrin Split Products
- aPTT: unfractionated heparin
- PT: Warfarin (WEPT)
- Bleeding Time: assessment of platelet function, would be increased in vWd, ASA therapy, DIC,
- Fibrinogen Levels: would be low in DIC
5 Fibrin Split Products, would be low in DIC
What is so special about the longevity of EBV
- when it infects B-cells via CD21, it stimulates them to enter the cell cycle and proliferate continuously (IMMORTAL). This happens by an EBV encoded oncogene activating proliferative and anti-apoptotic signaling pathways within the infected B-cell.
- Keep in mind the dx of EBV is the production of heterophile antibodies (meaning react with foreign antigen such as hoarse erythrocytes
PFTs in Obstructive vs Restrictive Lung Disease
Restrictive Lung Disease: Decreased FEV1 but MORE of a decrease FVC leading to an INCREASE IN THE RATIO. Decreased TLC
“Restrictive Raise”
Obstructive: Decreased FVC but decreased MORE the FEV1 leading to a DECREASE IN THE RATIO. Increased TLC as well.
“Obstructive is Obsolete”
Electrolyte Disturbances of a CF pt?
-HYPOnatremic
- They are salt wasting from sweat because sodium is NOT reabsorbed through the CFTR due to a mutation (deltaF508)
- Risk factors for a CF pt would be excessive temperature, excessive exercise and the newborn period when they are solely on breastmilk and not eating salty foods yet (all pre-dispose to hyponatremia)
- NOTE, these pts are also HYPOCHLOREMIC, but this is asymptomatic.
Where in the TCA cycle is GTP produced and what is it a subsequent cofactor for?
- Succinyl CoA –> Succinate (near the bottom of the circle)
- This is called substrate level phosphorylation and is carried out by the enzyme Succinyl CoA synthase
- The GTP is then a cofactor for PEP-CK in gluconeogenesis going from oxaloacetate to PEP.
Absence of CD18
-Leukocyte Adhesion Deficiency (LAD). Defect in LFA1 integrin on CD18, leading to impaired migration and chemotaxis. CANNOT form integrins, which are essential for leukocyte adhesion
-presents with recurring skin and mucosal infections, and periodontal disease
Also see late separation of umbilical cord (>21 days)
What is the cause of the greenish color in bruises?
- Erythrocytes escape into interstitum after injury and give blue/purple color
- Erythrocyte destruction then causes release of heme molecules
HEME OXYGENASE comes along (inside macrophages) and converts Heme–>Billiverdin (which is green in color)
The Billiverdin is then further broken down to billirubin (yellow) and is then bound to albumin and taken to liver
Mechanism of abx resistance
- Penicillins
- Vancomycin
- Quinolones
- Aminoglycosides
- Tetracyclines
- Rifamycin
- PCN –> beta-lactamase, mutated PBP, mutated porin protein
- Vancomycin –> mutated peptidoglycan cell wall (d-ala, d-lac)
- Quinolones –> Mutated DNA gyrase, impaired influx/efflux
- Aminoglycosides –> bacterial transferase enzymes that acetylate, adenylate, or phosphorylate
- Tetracyclines –> influx/efflux
- Rifamycin –> mutated RNA polymerase
Spinal Muscular Atrophy=Werdnig Hoffmann Disease
Congenital degeneraton of anterior horns of spinal cord. LMN lesions resulting in “floppy baby” with marked hypotonia.
- Caused by mutations in SMN1 gene which involves assembly of small nuclear ribonucleoproteins snRNP.
- impaired SPLICESOME fxn (removes introns from pre-mRNA)
Uses of these monoclonal antibodies
- Infliximab
- Rituximab
- Interleukin 2
- Imatinib
- Abciximab
1. Infliximab: IgG1 monoclonal antibody against TNFalpha. Use in RA, AS, Crohns
2. Rituximab: targets CD20 B-cells used in lymphoma
3. Interleukin 2: cytokine that regulates activation and differentiation of T-cells. Use in Renal Cell Carcinoma and Melanoma
4. Imatinib: tyrosine kinase inhibitor used in CML
5. Abciximab: against platelet GP11B/IIIa receptor, used during angioplasty for pts with ACS
Finding of green, inspissated (thickened/congealed) mass in distal ilius in newborn points towards what and what disease associated with and what will this pt ultimately die from?
Inspissated mass (dehydrated meconoium) in distal ilium points to a diagnosis of meconium ileus which is very common in CF pts.
- If you habe meconium ileus you will almost certainly be diagnosed with CF but if you have CF only about 10-20% of infants will have meconoim ileus
- Ultimately CF pts usually die of pneumonia (or cor pulmonale, bronchiectasis)
What is NOT supplied in breastmilk and needs to be supplmenented by mother?
Vitamin K and Vitamin D
-The Vitamin K is supplemented by a shot at birth
-Vitamin D is usually supplemented by some sunlight (harder to get in AA babies because of an increase in melanocytes acting as a natural sunblock)
“KD for the KiD”
Pt with Rheumatic Fever is most likely to die from what?
- Die from pancarditis (inflammation of the endocardium, myocardium, and pericardium)
- Inflammation of the mitral valve is also common and will result in a holosystolic murmur
- Severe regurgitation and myocarditis can lead to cardiac dilation, cardiac failure and DEATH in a very small number of pts
- Pt will NOT die of septic shock from the S. aureus because the disease itself of rheumatic fever with migratory arthritis is autoimmune and NOT caused by the bacteria at this point.
Supprative Parotitis
-an acute viral or bacterial infection of the parotid gland
-S. Aureus is the most common cause.
-Risk factors include dehydration, intubation, anticholinergics, salivary calculi, or recent teeth cleaning
Dx: AMYLASE, US/CT
-Think about this in a pt who has acute jaw pain post intubation in a hospital
Treatment of BV
-Metronidazole or Clindamycin
Dx: grey or clear discharge with fishy smell. Use KOH to increase the smell “Whiff Test”
-Also dx with presence of CLUE CELLS
Diagnosis of Down Syndrome in vitro is suspected by?
- Decreased maternal serum AFP
- Increased nuchal translucency
- Increased b-hCG
It is then confirmed by chorionic villus sampling or amniocentesis
Why do you get oxalate kidney stones with Crohn’s Disease?
when the wall of the terminal ilium is inflamed, bile acids are not reabsorbed. This loss of bile acid reabsorption causes an decrease in fat absorption. These excess lipids in the bowel bind to calcium essentially performing a supponification reaction and these soap complexes are lost in the feces
-As a result, oxalate cannot be bound by calcium (like it noramally is) and is taken up in the bowel. This leads to an increase risk of kideny stones
Desflurane
- A newer agent of the halothane class that is used for anesthetics and can lead to acute hepatitis.
- It is associated with a centrilobular hepatic necrosis
- Presents 2-3 days after exposure with fever, nausea, jaundice, scleral icterus, and increased liver enzymes
Ischemic Stroke Timeline
12-24 hours
24-72 hours
3-7 days
1-2 weeks
>2 weeks
12-24 hours –> “Red Neurons” (eosinophilic cytoplasm, loss of nissel substance)
24-72 hours –> neutrophilic infiltration
3-7 days –> macrophage/microglia infiltration and phagocytosis begin
1-2 weeks –> reactive gliosis and vascular proliferation around the necrotic area (liquefactive necrosis)
> 2 weeks –> glial scar formation
Pathology of a Hashimoto Thyroiditis pt
- intense mononuclear infiltrate consisting of lymphocytes and plasma cells often with germinal centers.
- Hurthle cells surround residual follicles
22q11.2 microdeletion
-DiGeorge Syndrome, neural crest cells fail to migrate into the 3rd and 4th pharyngeal pouches. Consequently end up with parathyroid and thymus hypoplasia. This results in hypocalcemia and T cell deficiency
-The hypocalcemia manifests as Chovstek and Troussou sign
Anencephaly
Failure of the anterior neuropore to close (can be prevented with folic acid supplementation during pregnacy)
Remnants of the Rathke Pouch could develop which tumor
-Craniopharyngioma resulting in hypopituitarism, hydrocephalus and diabetes insipitus
Post MI pt put on med with side effect of increased creatine kinase and muscle aches? what is med and what are some other side effects?
- Pt is clearly on a statin, an HMG coA Reductase inhibitor and is having stain-induced myopathy
- Statins block conversion from HMG CoA –> Mevalonic Acid, this decrease liver cholesterol leads to an increase in LDL clearance by the liver by LDL receptors. These LDL receptors endocytose the LDL and then are recycled for use again
also causes an upregaultion of HMG CoA reductase enzyme since it is all being blocked!
Latissimus Dorsi innervation and actions
Innervated by Thoracodorsal Nerve (from C6-C8 nerve roots)
Actions: Internal rotation of arm, extension, adduction of arm
A very vulnerable muscle to external injury
Refractory asthma treatment (when oral glucocorticoids and long acting beta adrenergic antagonist are NOT working)
-Omalizumab is an IgG monoclonal antibody that binds with IgE to inhibit the action of IgE on mast cells, basophils, or other cell types and decreases allergic response. (anti IgE antibody)
Canagliflozin
SGLUT-2 Inhibitor used for TII DM
Usually SGLUT-2 reabsorbs 90% of glucose from filtrate in the proximal tubule.
This drug leads to significant loss of urine glucose
Side effects: UTI’s (due to lots of glucose in urine feeding bacteria), systemic hypotension. Should be avoided in pts with moderate to severe renal impairment
-MUST CHECK RENAL FUNCTION PRIOR TO USE
3 causes for Down Syndrome
1. Nondisjunction (95%): extra chromosome 21 in EVERY cell, due to increased MATERNAL age
- Unbalanced translocation (2-3%): all or part of additional chromosome 21 attached to another chromosome
- Mosaicism (<2%): the nondisjunction event occured early on and the pt has two disctinct cell lines in their body. The proportion of cells affected are what determines severity of disease
The relationship between ACh and Alzheimer Disease
- a decrease in ACh level due to a DEFICIENCY of choline acetyltransferase. This is most notable in the basal nucleus of Mynert, which participates in memory and cognition. ALSO involves hippocampus which is obviously involved in new memory formation
- AChE-I are meds used to treat Alz =Donepezil, Galantamine
What medication experiences fast and slow acetlyation and happens with what other meds?
Isoniazid
- Slow acetylation: convert drug slowly and result in an increase in the plasma concentration…also happens with Dapsone, Hydralazine, and Procainamide
2. Fast acetylation:may require higher dose to achieve same therapeutic effect
The single most effective preventative intervention that pts can do to decrease mortality risk
- STOP SMOKING
- this is more of an effect than diet or exercise (these effect cardiovascular health but smoking has profound effect on so many different systems in the body)
Surgery to remove thyroid and now all of a sudden have sx of hypocalcemia, why?
Surgery removed parathyroid as well and now the pt is not reabsorbing the calcium in the kidneys anymore
This is called symptomatic hypoparathyroidism due to inadvertant removal of parathyroid
-phosphate reabsorption would also be decreased in these pts
alpha-galactosidase A deficiency found in what disorder and what are some of the clinical features?
- Fabry, (XL-R) results in buildup of Gb3
- neuropathic pain, and hypohydrosis are the first sx
Can also see CVA, CVD which are obviously most common cause of death
telangectasia later on
The buildup of Gb3 reuslts in proteinuria and polyuria and eventual RENAL FAILURE
Fimbriae is another word for ___and is a virulence factor for what?
Pilli
E.Coli
COPD exacerbation tx (not specific med, just mechanism)
- Beta adrenergic agonist (produce relaxation of bronchial smooth muscle by stimulating beta-2 adrenergic receptor)
- This acts via Gs –> increase cAMP
- Asthma and COPD are the most frequent causes of pulsus paradoxus in the absence of signficant pericardial disease
Walk through how a tumor in outer layer of adrenal cortex presents
This tumor is affecting the zona gomerulosa which produces aldosterone. Aldosterone acts on the distal collecting duct (principal cells) to increase the absorption of Na and dump out K and H. This if a tumor were producing too much Aldo, you would see a hypokalemic, metabolic alkalosis. These would lead to parasthesias and muscle weakness
This mimics Conn Syndrome
Where does the clot come from in AFIB?
L atrial appendage
Overactive bladder pathophys and treatment
-caused by uninhibited bladder contractions (detrusor instability). Causes a sense of urgency and involuntary leakage
Best treatment is with anticholinergic drugs = oxybutynin, which antagonizes M3 receptors on bladder
What medications MUST be avoided in a pt with Hypertrophic Cardiomyopathy?
Vasodilators: (CCB, nitro, ACE-I) lead to decreased afterload and lower LV volumes
Diuretics: decrease LV filling (preload) and result in greater outflow obstruction
Actinomycosis
- slow progressive disease caused by the gram + anaerobic bacteria Actinomyces Isralii
- usually colonize mouth, colon and vagina and can be found in dental caries
- Most frequently presents with cervicofacial abscesses
- Pulm actinomycosis is rare but usually occurs because of aspiration.
Dx: filamentous branching, sulfur granules
Tx: PCN
What property of elastin allows it to stretch during active inspiration and recoil during expiration
-Interchin cross-links involving LYSINE made by lysyl oxidase (requires Copper as a cofactor). This forms desmosine cross-links between elastin monomers
Disulfide bridges are made in COLLAGEN NOT ELASTIN
Elastin is made in Alveolar Macrophages
OSA treatments
- Stimulate hypoglossal nerve (causes tongue to move forward slightly)
- CPAP
- surgery
- wt loss
Ipatroprium mechanism
-anticholinergic agent used for acute asthma attacks that blocks muscarinic receptors (M3), preventing bronchoconstriction
Side effect is increased drying
Two types of H. Infleunzae
- Nontypeable are unencapsulated and are the cause of MOST mucosal infections (otitis media, conjunctivitis, bronchitis) 90% of strains isolated from the middle ears of children are this type
- H. Influenza Type B (Hib) are responsible for the other 10% of infections. These are capsulated and there is a VACCINE for this type
All children should get this vaccine by 2 months of age to help protect from EMOP (epiglottitis, meningitis, otitis media, and pneumonia)
What are the neurological symptoms caused by in a panic attack?
-Hyperventilation leading to hypocapnia, which can cause decreased cerebral perfusion and altered mental status
Very high fever, diarrhea, confusion, and a cough that may only be slightly productive is indicative of what??
what is tx?
- Legionnaire’s Disease
- one of the most common causes of community acquired pneumonia
- commonly contaminates water sources such as tap water, air conditioners, or other water based cooling systems
tx: floroquinolones and macrolides
Lobar Pneumonia stages (4)
- Congestion (first 24 hours): area is red, heavy, boggy. Alveolar exudate contains mostly bacteria
- Red hepatization (days 2-3): Red, firm lobe (liver like consistency) Erythrocytes, neutrophils and fibrin present
- Grey Hepatization (days 4-6): Gray-brown firm lobe. RBC disintegrate,
- Resolution: restoration of normal architecture
Dyspnea, Bibasilar Crackles, and presence of S3 are indicative of what??
what does this presence of extra fluid indicate??
-Left sided heart failure
-The extra fluid increases resistance to movement and can lead to decreased lung compliance resulting in poor gas exchange and shortness of breath. Other causes of reduced compliance include pulmonary fibrosis and insufficienct surfactant
SaO2 and PaO2 cutoffs for hypoxic erythrocytosis to begin
SaO2 < 92%
PaO2 < 65 mmHG
This is a chronic process, would result in an increase RBC mass (increase retic count) due to increase EPO
Polycythemia HCT level cutoffs
- Men >52% Hct
- Women >48% Hct
Then need to differentiate if it is an absolute increase or a relative increase –> need to measure RBC mass (not just Hgb and Hct). If RBC mass is normal, indicates a plasma constriction and relative increase in Hct. If the mass is elevated, must differentiate between Primary and Secondary erythrocytosis by EPO levels (primary have low EPO (myeloproliferative disorder)) (secondary is due to chronic hypoxia from altitude, smoking, COPD)
What must you tell a pt after inhaled glucocorticoids??
- use a spacer
- Rinse mouth out
If get too much residual glucocorticoid in the mouth can predispose to Candida infection
What is a CGD pt most susceptible to and why?
Most susceptible to Catalase + organisms. CGD is missing NADPH oxidase complex, which produces superoxide, hydroxyl radicals, and hydrogen peroxide.
Pts are susceptible to:
S. Aureus
Burkholderia
Serratia
Nocardia
Aspergillus
McArdle Disease
-Deficiency in myophosphorylase
NO rise in blood lactate levels after exercise
Decrease in this enzyme results in poor exercise tolerance, muscle cramps, rhabdomyolysis
-Can be tolerated by drinking glucose drinks DURING exercise. Not a tx
why would a newborn with cystic fibrosis present with an intercranial hemorrhage?
-They are defienct in fat absorption, thus are defieient in ADEK vitamins, thus are more prone to life-threatening bleeding (esp from the lack of Vit K…making 2,5,7,9,C,S)
Noise induced hearing loss stems from what?
-Trauma to stereociliated hair cells in the organ of corti. High frequency hearing is lost first
Remember:
- Hearing frequency at auditory nerve is more likely schwannoma
- Cochlear Cupula is responsible for low frequency sounds
- Defects of middle ear bones (otosclerosis) affects AIR conduction over ALL frequencies
- Malformation of ROUND window is more likely congenital
- Rupture of tympanic membrane causes unilateral conductive hearing loss
Chronic Myeloproliferative Disorders (4)
Bone marrow diseases caused by overproduction of myeloid cells
- Chronic Myelogenous Leukemia (BCR-ABL 9;22): leukocytosis with LEFT shift
- Essential Thrombocytosis (JAK-STAT): thrombocytosis
- Polycythemia Vera (JAK-STAT): erythrocytosis
4. Primary Myelofibrosis (JAK-STAT): atypical megakaryotipic hyperplasia, which stimulates fibroblast production which results in progressive replacement of bone marrow by collagen deposition. BONE MARROW FIBROSIS, SEVERE FATIGUE, HEPATOSPLENOMEGALY
Chromosomal Disorders
3
4
5
7
9
11
13
15
17
18
21
22
X
3 VHL, Renal Cell Carcinoma
4: ADPKD (w/ PKD2), Huntington
5: Cru-du-Chat, Familial adenomatous polyposis
7: CF
9: Fredreich Ataxia
11: Wilms tumor
13: Patau, Wilson’s
15: Prader Willi, Angelman
17: NF1
18: Edwards
21: Down
22: NF2, DiGeorge
X: Fragile X, X-linked Aggamaglobulinemia, Klinefelter
3 AA associated with maple syrup urine disease
(I LOVE VERMONT maple syrup! from maple trees with B1ranches)
-Isoleucine, Leucine, Valine
Due to branched chain alpha-ketocacid dehydrogenase complex (BCKDC)
Requires thiamine B1 as a coenzyme**
Where does H. Pylori live mostly?
Antrum of stomach (where there are the fewest acid secreting parietal cells)
Virulence Factor of Streptoccus Pneumonia
polysaccharide capsule (prevents phagocytosis)
- this capsule is antigenic and Ab are created against it which confers immunity against that particular strain
- the pneumococcal vaccine confers generates immunity against some common strains (capsule specific)
Most common immune cells present with Crohn’s
Th1
IL-2
INF-Y
Terminal ilium is the most common location of crohns, has cobblestone appearance. Non-caseating granulomas and an inflammatory infiltrate that involves all layers of the wall (transmural) is common
Th2 are more involved in UC!!
Most cases of hemolytic uremic syndrome are associated with??
-E. Coli 0157:H7 due to production of Shiga-like toxin (so obviously can see this in Shigella TOO)
HUS: thrombocytopenia, renal insufficiency, microangiopathic hemolytic anemia
HPV infections of respitatory tract affect where specifically?
-Has a prediliction for stratified squamous epithelium
In the respiratory tract, the only stratified squamous is the TRUE VOCAL FOLDS (think about the constant beating these cells take and they need to be replaced frequently)
False vocal folds, paranasal sinus, trachea: pseudostratified columnar to help protect from foreign bodies
alveoli: simple squamous
“It would truly suck to get HPV in the throat”
Innervation of ear and area around the ear
Majority of area around ear is great auricular nerve (anterior) and great occipital nerve (posterior)
ALTHOUGH, the posterior part of the external auditory canal is innervated by small auricular branch of the VAGUS NERVE
That little bit right inside your ear that is telling you to go to Vegas
Gram - sepsis caused by___
-Release of LPS from bacterial cells during division or bacteriolysis. LPS is NOT ACTIVELY SECRETED
Lipid A is the toxic component of LPS, which causes activation of macrophages leading to widespread release of IL-1 and TNF-alpha
Low dose vs high dose Dopamine administration
Low Dose: stilumates D1 receptors to increase RBF, GFR, and sodium excretion. Mesenteric vasodilation occurs at this level
High Dose: stimulate B1 adrenergic in the heart increaseing pulse pressure, cardiac contractility, and systolic blood pressure
At even higher doses: stimulates Alpha-1 to cause systemic vascoconstriction, which results in decreased CO due to increased afterload (pressor effect)
DBA looks like DoPA or DOBA
Constrictive pericarditis physical exam findings
-Thick fibrous shell that restricts ventricular volumes causes low cardiac output and R sided heart failure
-jugular venous pressure increases (normally this drops during inspiration due to increase in negative pressure) however in these pts, see a paradoxical rise in jvp (KUSSMUAL SIGN)
-Can also hear pericardial knock, which occurs earlier in diastole than S3.
Giant Cell Arteritis mediator
- IL-6 appears to closely correlate with the severity of the disease
- Remember that this temporal arteritis is associated with polymyalgia rheumatica and is the most common vasculitis in pts over 50
Cell mediated process with particular increase in
IL-6
Also see increase in ESR
Most common cause of nephropathy in the US and what is the pathophys and timeline?
Diabetic Nephropathy (for both Type I and Type II)
- The earliest changes are glomerular basement membrane thickening with resultant mesangial matrix expansion. Also see hyaline arteriolosclerosis (in the intima and media of small arteries and arterioles)
- In initial stages, loss of negative charge of GBM leads to microalbuminemia
Tx: ACE-I have been shown to decrease the protein lost in the urine and slow the progression of GBM thickening
Loss of sensation in the perineal area?
-Cauda equina syndrome, which is commonly due to epidural cord compression from a malignancy. Pts usually develop urinary incontinence late in the disease with fecal incontinence as well
Major eosinophil functions (2)
1. Parasite defense: stimulated by Il-5 (promotes class switching to IgA) via Th2 and mast cells. The parasite invades the system and is coated in IgE and IgG antibodies that bind the Fc receptors of eosinophils. This triggers release of major basic protein that destroys the parasite. This is an example of antibody dependent-cell mediated cytotoxicity
2. Type I hypersensitivity reactions: eosinophils also synthesize prostaglandins, leukotrienes and cytokines that contribute to late phase type 1 hypersensitivity and chronic allergic reactions
Antiphospholipid Antibody Syndrome
- presence of antiphospholipid antobodies in the setting of thromboembolism and reccurent miscarriages
- This may be a primary disorder or a disorder secondary to SLE
Remember that SLE can present with a false positive RPR/VDRL test and + antiphospholipid antibodies
What does angiotensin II do to the efferent arterioles of the kidney?
-a POTENT vasoconstrictor that constricts the efferent arteriole and restores GFR
Which part of the nephron responds to vasopressin??
-MEDULLARY segment of the collecting duct and CORTICAL segment
Medullary: production of maximally concentrated urine since this region deals with the HIGHEST osmolarity in the kidney
Cortical: reduces amount of free water delivered to the medulllary collecting duct
Hypoalbuminemia causes what effect on oncotic pressure?
-LOWERS oncotic pressure and causes interstitial edema due to net plasma filtration
Is H2PO4 increased or decreased in urine of DKA pt?
-Increased
This is an acid buffer in the urine that is used to trap free H+ and keep it so the pH does not lower too much
HPO4 and NH3 are the two most important acid buffers in the lumen of the kidney –>they become H2PO4 and NH4
**NH3 is the more important of these two as the kidney can greatly increase NH3 production in chronic acidosis***
How to calculate Filtration Fraction in kidney?
FF=GFR/RPF
This is the fraction of plasma flowing through the glomeruli that is filtered across the glomerular capillaries into Bowman’s Space
RPF can be determined using the PAH clearance as almost ALL of the PAH is excreted in the urine. GFR can be estimated by looking at how much creatinine because this is freely filtered (could use inulin also)
The clearance of anything can be calculated as
Cs=(urine concentration x urine flow rate)/plasma concentration
Note: that 20% is a normal FF for healthy ppl
Ethylene Glycol effects on kidney
- Leads to TOXIC, acute tubular necrosis with vacuolar degeneration and ballooning of the proximal tubular cells
- Would find high ANION GAP METABOLIC ACIDOSIS
- Calcium oxalate crystals in the urine
What part of the kidney does Lithium act on?
-The principle cells of the collecting duct is where lithium can induce diabetes insipitus as a result of lithium’s antagonizing effects on the action of vasopressin
Spike and Dome appearance of the glomerular basement membrane
Seen in Membranous Glomerulopathy
85% of these cases are idiopathic
The remaining cases are due to DM, tumors, SLE, gold, penicillamine, NSAIDS, hep B, hep C, malaria, syphilis
Chronic Kidney Disease Labs
(GFR, VitD, Phos, Ca, PTH)
Starting with a decreased GFR
Decreased 1-25 dihydroxy vitamin D –> decreased intesinal Ca absorption
Phosphate retention –> high serum phosphate
LOW serum Calcium
HIGH PTH synthesis
Secondary HYPERPARATHYROIDISM
What is the cause of Turner Syndrome
-Paternal Meiotic Nondisjunction
The loss of the X-chromosome results in loss of SHOX gene, which is resonsible for long bone growth (reason why pts with Turner have short stature)
Surgical oophrectomy if the surgeon wants to avoid excessive bleeding need to ligate what??
-Suspensory ligament of the ovary
This is what contains the ovarian artery, vein, lymphatics and nerves
**This is the SAME ligament (=infundibulopelvic ligament) that is twisted in ovarian torsion**
Which of these contains an artery? (esp in regards to removing an ovary)
- suspensory ligament of ovary
- mesosalpinx
- ovarian ligament
- Round ligament of the uterus
- Transverse cervical ligament (Cardinal ligament)
- suspensory ligament of ovary –> contains ovarian artery (need to cut for removal of ovary)
- mesosalpinx –> region of broad ligament below fallopian tubes and does NOT contain artery
- ovarian ligament –> connects ovary to side of uterus (NO blood vessels)
- Round ligament –> contains artery of Sampson (not really of consequence when removing ovary)
- Transverse cervical ligament –> from cervix to lateral fornix of vagina. Uterine artery does course in superior portion but not relevant for ovarian removal
Most common cause of septic abortion
S. Aureus (gram- bacilli too, like E. Coli and GBS but less common)
Usually an abortion resulting from any retained products of contraception in the uterine cavity
This usually presents as fever, abd pain, uterine tenderness, foul smelling discharge after pregnency termination
Pt has an enlarged uterus and complains of menorrhagia and dysmenorrhea most likely has what??
Adenomyosis which is the presence of endometrial glandular tissue within the myometrium
Best way to test for trichomonas
-Saline microscopy (wet prep) looking for motile protazoan
Usually presents as thin, yellow, mucous discharge that is foul smelling
Tx: metronidazole
Prior to delivery, estrogen stimulates the upregulation of what inside smooth muscle cells?
Gap junctions to heighten myometrial excitation. Gap junctions consist of aggregated connexin proteins that allow passage of ions between myometrial cells
Gastric tumor that metastasizes to the ovary and what are the pathological findings?
Kruckenberg Tumor with classic histologic feature of signet ring cells. These cells appear this way due to a large amount of mucin that displaces the nucleus to the side of the cytoplasm
Postpardum bleeding can be controlleg by ligating what artery and still keeping fertility possible?
- The uterine arteries are the main blood supply to the uterus and are brachnes off of the internal iliac artery. Bilateral ligation of the internal iliac arteries would stop uterine blood flow and prevent the need for hysterectomy
- The uterus has collateral blood flow from the ovarian arteries so the blood supply will not be completely cut off
Episiotomy cuts where and what?
This is a cut made from the posterior vaginal opening to the perineal body to enlargen the vaginal outlet to facilitate delivery and reduce the risk for severe perineal laceration
The external anal sphincter, rectal mucosa, levator ani, ischiocavernosus muscle and transverse perineal muscle are NOT cut
During menstruation what is the process at a cellular level?
These cells undergo progesterone withdrawl, leading to a prostaglandin increase, which leads to vasoconstriction of the spiral arteries
The progesterone withdrawl also leads to increased metalloproteases by endometrial stromal cells leading to APOPTOSIS of endometrial epithelium and sloughing of the wall.
What type of tissue lines the ovary, fallopian tube, uterus, cervix vagina?
Recombination (of viruses)
- exchange of genetic information between two nonsegmented, double stranded DNA genomes. This is the exchange of genes between two chromosomes via crossing over within homolglogous chromosomes
- Unlike Reassortment, which refers to changes in genomic composition that occur when host is coinfected with 2 SEGMENTED viruses that echange whole genome segments
- The herpes virus is NOT segmented, so it cannot undergo reassortment
Cephalosporin-resistant organisms
Listeria monocytogenes (resistant PBP)
MRSA (resistant PBP)
Enterococci (resistant PBP)
Atypicals such as mycoplasma and chlamydia (no cell wall)
Treat listeria with ampicillin. Remember, listeria causes disease in those with deficient cell-mediated immunity such as pregnant ladies, young infants, or immuocompromised patients
Common diseases associated with these:
Borellia Burgdorferi
Pasturella Multocida
Actinomyces israelii
Bacilus anthracis
Rickettsia Rickettsiae
Borellia Burgdorferi: Lyme Disease
Pasteurella Multocida: oral flora of cats and dogs
Actinomyces Isralii: oral abscesses with dranining yellow pus
Bacilus Anthracis: cutaneous anthrax. Release Edema factor and Lethal factor creating a papule that eventually is covered with black eschar. Tx: Ciprofloxacin
Rickettsia Rickettsiae: Rocky Mountain Spotted Fever (erythematous macules that migrate centripetally toward the trunk)
Daptomycin mechanism and uses and adverse effects
- Can be used to treat MRSA (along with vancomycin and linezolid)
- The mechanism is that it disrupts the bacterial membrane by creating transmembrane channels that cuase intracellular ion leakage. The resulting cellular membrane depolarization and macromolecular (DNA/RNA/protein) synthesis inhibition leads to cell death.
- It also binds to and is inactivated BY pulmonary surfactant (so it is ineffective in treatment of pneumonia)
Adverse: increased CK levels and increase incidence of myopathy, esp in pts taking statins
How do you treat recurrence of genital HSV?
It can be suppressed or minimized with oral valacyclovir (preffered over valcyclovir as it is dosed once daily and has good bioavailability). Could use daily acyclovir or famcyclovir
-These are not great at being active against latent virus forms, but can suppress multiplication as SOON as reactivation occurs.
A short 7-10 day course of oral acyclovir doesn’t do anything for recurrence rates, it only helps with the lesional healing time and local pain.
Aspiration Pneumonia vs Aspiration Pneumonitis
Aspiration Pneumonia: lung parenchyma INFECTION. Aspiration of upper airway or stomach MICROBES (anaerobes). Presents DAYS after aspiration event. see FEVER, cough, increase sputum. CXR infiltrate in dependent lung segment (classically RLL). Can progress to abscess. ABX: Clindamycin or B-lactam and B-lactamase inhibitor
Aspiration Pneumonitis: Lung parenchyma INFLAMMATION. Aspiration of GASTRIC ACID with direct tissue injury. Presents HOURS after aspiration event. Range from no sx, to nonproductive cough, decreased O2. CXR: infiltrates resolve WITHOUT abx. Tx: supportive
HSV-1 first clinical sign
- Gingivostomatitis is the first sign and due to its painful nature, the pt opts NOT to drink fluid and often presents to the ER with dehydration
- Peak age for primary infection is 6months to 5 years
Most common microorganisms for Cat Bites, Dog Bites, and Human Bites
Cats: Pasteurella (most common) has characteristic mouse-like odor, Bartonella (lymphangitis in immunocompromised pts
Dogs: Pasteurella, Streptococci, S. Aureus
Human: Anaerobes, Streptococci, Eikenella corrodens (clenched fist injury “fight bite”)
Toxic Shock Syndrome Toxin (TSST) mechanism
-Acts as a superantigen that activates a large number of helper T cells
This results in release of IL-2 from T cells and IL-1 and TNF from macrophages
This immune cascade is what is responsible for TSST sx
Q Fever is caused by?
Coxiella Burnetti: usually through inhalation of air that has been contaminated by animal waste
Acute: nonspecific febrile illness (HA that are retroorbital, pneumonia, thrombocytopenia)
Chronic: Can be fatal if not treated
Left shift of oxy hemoglobin dissociation curve has what effect on RBC number?
This low oxygen level would stimulate the kidney to produce more EPO, which would result in a compensatory erythrocytosis to maintain normal oxygen delivery
What do these cells do?
CD4
CD8
CD15
CD16
CD19/CD20/CD21
CD4: helper T-cell marker
CD8: cytotoxic T cell
CD15: cell surface marker present on granulocytes. It is also present in nearly all Reed Sternberg cells and is therefore useful in the diagnosis of Hodgkins Lymphoma
CD16: low affinity Fc receptor found on the surfaces of NK cells, macrophages, and neutrophils
CD19/CD20/CD21: found on B-cells (both immature and mature)…would see low in X-linked Agammaglobulinemia
Cholesteatoma
- Overgrowth of desquamated keratin debris within the middle ear space. May erode ossicles, mastoid air cells and lead to CONDUCTIVE HEARING LOSS
- Forms a round, pearly mass behind the tympanic membrane
- Can be primary or secondary to trauma, infection, surgery.
- Painless
- Can cause small perforation in the tympanic membrane
Pt with Hepatic Encephalopathy, what is going on in his astrocytes?
- There is increased levels of ammonia and other toxins circulating around in the body due to an inability to metabolize by the liver.
- With excess amonia, this is taken up by astrocytes, increasing glutamine production. This leads to increased osmolarity inside of the astrocytes causing swelling and impaired glutamine release
- Hyperammonemia decreases the amount of glutamine available for conversion of glutamate in neurons resulting in decreased excitation
How does an RPR test actually work??
Serum is mixed with a solution of cardiolipin, lecithin, and cholesterol. If aggregation or “floccation” is seen this is indicative of antibodies against cardiolipin
-This is a non-treponomal specific test, instead it is detecting antobodies to human lipids that are released as a result of cellular destruction by Treponema Pallidum (is positive in yaws, pina, bejel)
Basic concept of diastolic heart failure (3 things involving EF, EDV, LVP)
- Normal left ventricular ejection fraction (>50%)
- Normal end diastolic volume
- Increased LV filling pressure
Chronic Bronchitis presentation
-Thickened bronchial walls with neutrophil infiltration and mucus gland enlargement (increased number of goblet cells) and patchy squamous metaplasia that is brought on by longterm smoking
Cheyne-Stokes Breathing
- Common in advanced heart failure pts
- this is a cyclical pattern that has periods of apnea followed by gradually increasing and decreasing tidal volumes that is followed by another apneic period
- It is also seen in stoke, brain tumors, and TBI’s and is often a poor prognostic sign
Types of breathing
Normal
Biot
Kussmaul
Cheyne-Stokes
Biot-periods of apnea and hyperpnea (only pathological)
Piriform recess has what function and covers what nerve?
- small cavities that lie on either side of the laryngeal orrifice. During swallowing, food is directed by the eppiglottis to the piroform recess and into the esophagus
- A thin layer of mucosa protects the internal laryngeal nerve that is a branch of the Superior Laryngeal Nerve (CNX). This contains only sensory and autonomic fibers (NO MOTOR, unlike recurrent laryngeal and external laryngeal)
- This mediates the afferent limb of the COUGH REFLEX
Gag Reflex vs Cough Reflex
Gag
afferent –> Glossopharyngeal Nerve
efferent –> Vagus nerve
Cough
afferent –> internal laryngeal nerve (branch of superior laryngeal nerve, branch off vagus)
efferent –> vagus
Treatment of oral Candida infection
Nystatin a polyene antifungal with a mechanism similar to amphotericin B. Binds to ergosterol molecules in the fungal membrane causing pores and leakage of fungal cell contents. It is NOT absorbed orally, so is given as an oral “swish and swallow”
could also use fluconazole, or caspofungin
What makes green color of pus?
-Neutrophil Myeloperoxidase a blue-green heme based enzyme that forms hypochlorus acid (bleach)
CGD is a disease that is missing what enzyme and what are you more prone to as far as infection?
Missing NADPH oxidase so more prone to catalase + organisms
C: Candida
A: S. Aureus
T:—-
A: Pseudamonas Aeruginosum
L: Listeria
A: Aspergillus
S: Serratia
E: E. Coli
(and Nocardia)
What will the pulmonary capillary wedge pressure be in someone in ARDS?
-It will be normal because the problem is noncardiogenic pulmonary edema
If the cap pressure was elevated, it is more suggestive of cardiogenic pulmonary edema
In ARDS you WOULD see:
- increased capillary permeability
- decreased lung compliance
- increased work of breathing
- oxygen diffusion capacity to decrease
- V/Q mismatch
Oral thrush, interstitial pneumonia, and lymphopenia in an infant is suggestive of what??
HIV infection that was passed mom–>infant
-Could have been avoided with Zidovudine (ZDV) a nucleotide reverse transcriptase inhibitor (enzyme inhibitor) given to the infant for several weeks.
The mom should have had a standard HAART administration of 2 nucleotide/nucleoside reverse transcriptase inhibitors and one third drug (protease inhibitor, NNRTI, integrase inhibitor)
Theophylline Toxicity
adenosine receptor antagonist and phosphodiesterase inhibitor that is used as an alternate therapy for Asthma and COPD. It causes bronchodilation by increasing cAMP levels
-It is metabolized by hepatic cytochrome oxidases, which can be inhibited by medications such as:
-Ciprofloxacin, Cimetidine, Macrolides, Verapamil
Toxicity presents as CNS stimulation such as seizures, tremors, insomnia as well as cardiac abnormalities (arrhythmias)
Granulomas in TB vs Sarcoidosis
TB: caseating granulomas
Sarcoidosis: NON-caseating granulomas
IL-2 Functions and drug
produced primarily by helper T-cells and is a major growth factor for T-lymphocytes
IL-2 also stimulates the growth differentiation and survival of CD4 and CD8 T cells.
**Stimulate the growth of helper, cytotoxic and regulatory T cells and NK cells
IL-2 as a drug is called Aldesleukin and is used for metastatic melanoma and renal cell carcinoma
Tumor Lysis Syndrome forms what and where (in kidney)
Happens when tumors are treated with chemotherapy. The lysis of tumors causes release of K, Phosphorus, Uric acid to be released into the serum
At physiologic pH, the uric acid is soluble, but in the acidic environment of the collecting tubule, they ppt into uric acid stones
This can be prevented by treatment with Allopurinol (Inhibit xanthine oxidase) to prevent tumor lysis syndrome
Pt with hypertension, hypokalemia, high aldosterone, high renin…how do you differentiate where problem is coming from?
Hyperaldosteronism can be divided into primary and secondary
Primary (Conn): There will be hypokalemia, hypernatremia, high aldosterone, LOW renin due to feedback inhibition of renin secretion
Secondary: overproduction of aldosterone is SECONDARY to excess renin production (renal artery stenosis, diuretic use, malignant hypertension, renin-secreting tumor
Nonaldosterone causes: CAH, deoxycortisone producing adrenal tumor, Cushing syndrome, exogenous mineralcorticoids. Would present with LOW aldo, LOW renin
Pt with MS has what type of bladder abnormalities?
-Spastic bladder: urinary frequency and urge incontinence due to the presence of an upper motor neuron lesion (is common in pts developing acute lesions in the spinal cord)
-The bladder does not destend/relax properly due to loss on inhibitory control from UMN
Multiple myeloma calcium happenings
Hypercalcemia due to osteolysis induced by tumor cells, which release osteoclast-activating factor.
This elevated serum Ca leads to decreased PTH production. The low levels of PTH lead to increased loss of Ca in urine (hypercalciuria)
The hypercalcemia and light chain cast nephropathy cause progressive renal failure. This leads to loss of 1-alpha hydroxylase resulting in low 1-25 Vit D.
Side effects of Foscarnet
-hypocalcemia and hypomagnesemia due to it being a pyrophosphate analog. It can chelate calcium
May lead to a reduction in PTH release, which would contribute to the hypocalcemia
Both hypocalcemia and hypomagnesemia can contribute to seizures!
Acetazolamide use outside of kidney
Used in acute angle glaucoma. Carbonic anhydrase modulates HCO3 formation in aqueous humor, so inhibition of CA will decrease aqueous humor production
Polyuria that responds to DDAVP? and what is the action of DDAVP on the kidney (2 things)
Must be central diabetes insipidus (because nephrogenic does not respond at all and central the problem is you just are not producting ADH)
Keep in mind that V2 acts on the kidney to increase aquaporin channels to bring water back in. UREA is also brought back in in the collecting duct in response to V2 in the inner medullary collecting duct, which increases the osmotic gradient in the medulla, which allows for the production of MAXIMALLY concentrated urine
Label this graph of tubular concentrations as you go along the PCT
What is the origin of Renal Cell Carcioma within the kidney?
and some other fun facts
The epithelium of the proximal renal tubules
It looks like polygonal clear cells filled with accumulated lipids and carbohydrates, often golden-yellow due to high lipid content (on macroscopic view)
Risk factors are smoking and obesity
Manifests clinically as hematuria, flank pain, palpable mass (triad that is not always presenting as triad)
Associated with paraneoplastic syndromes (ACTH, EPO, PTHrp, renin)
Tx: Aldesleukin (IL-2)
Dobutamine
B-agonist predominantly B1>B2 that is a simpathomimetic used in heart failure used in management of refractory heart failure associated with LV dysfunction and cardiogenic shock
+inotrope
weakly + chronotrope (this increases HR and thus increases myocardial O2 consumption). Although this can trigger or exacerbate myocardial ischemia, it is weighed against the benefit of end organ perfusion and improvement of cardiac output vs the drawback of cardiogenic shock
Zenker Diverticulum formation
abnormal spasm or deminished relaxation of crycopharyngeal muscles during swallowing is thought to be the mechanism behind Zenker Diverticulum
- Results in an early oropharyngeal dysphagia that presents as a feeling of food obstruction in the neck area
- Pts develop halitosis/regurgitation
- Pulmonary aspiration is common as well leading to pneumonia
NOT A TRUE DIVERTICULUM (not all layers)
Olanzapine side effects (and Clozapine)
Olanzapine=Obesity
This is a second generation antipsychotic. Commonly used first line since it does not have any of the extra-pyramidal side effects that first gen antipsychotics (haloperidol) have.
Olanzapine and Clozapine both have the highest metabolic side effects and it is wise to check fasting glucose and lipid pannel several months down the road when pts are on these drugs
Clozapine can also have agranulocytosis (requires weekly WBC monitoring) Must watch CLOZAPINE CLOZELY
At what point in the breath cycle is pulmonary vascular resistance LOWEST?
-It is lowest at the functional residual capacity (right at the bottom level of the tidal volume)
-Increased lung volumes increase PVR due to longitudinal stretching of the alveolar capillaries by stretching the alveoli
-Decreaed lung volumes increase PVR due to decreased radial traction from adjacent tissues on the large extra-alveolar vessels.
Give examples of:
Type 1 Hypersensitivity
Type 2 Hypersensitivity
Type 3 Hypersensitivity
Type 4 Hypersensitivity
Type 1 (immediate, IgE): anaphalysis, allergies
Type 2 (cytotoxic, IgG and IgM autoantibodies): Autoimmune Hemolytic Anemia, Goodpastures
Type 3 (immune complex, antigen-antibody complex) with complement activation: PSGN, Lupus, Serum Sickness
Type 4 (delayed type, T-cells and macrophages): Contact Dermatitis, TB skin test
What nerve supplies Deltoid and Teres Minor
Axillary, originates from posterior cord and carries fibers from C5 and C6
Filtration fraction calculation (and normal %)
FF=GFR/RPF =20% is normal
RPF=RBF (1-hct)
Contraindications of buproprion
- Seizure pts
- Anorexia pts
Bicuspid Aortic valve risk?
Risk of aortic stenosis at age 50!!! due to calcifications and premature atherosclerosis. This is 10-15 years before the normal tricuspid aortic valve starts to see it from normal senile calcific stenosis
A lesion involving the superior orbital fissure has what effect?
-Would eliminate the sensory portion of the corneal reflex that is a branch of the Trigeminal Nerve (the nasociliary branch of the first division of the trigeminal nerve). This enters skull at superior orbital fissure
-Eye adduction via medial recuts muscle that is innervated by the occulomotor nerve (CN3) that enters via superior orbital fissure as well
Fibromyalgia
widespread muscular pain with associated fatigue.
- effects women 20-55 most commonly
- Unknown etiology but likely involves abnormal central processing of painful stimuli
Can be exacerbated by excercise although can be aleviated by incremental aerobic exercise.
Can be treated with TCA, SNRI
4 steps of leukocyte accumulation
- Margination: increased vascular leakage improves contact of neutrophils with endothelial lining
- Rolling: roll on endothelium via lose binding of Siacyl Lewis X to E-selectin, P-selectin on macrophages, L-selectin on neutrophils
- Activation: slow rolling allows neutrophils to sample the chemokines associated with the inflammed tissue
- Tight adhesion: CD18 to ICAM1
- Transmigration: via integrin attachment and adherence to PCAM-1. This protein is found at the peripheral intercellular junction of endothelial cells
Fibrates (gemfibrozil and fenofibrate) actions
- used to lower triglycerides
- Activate PAR-alpha which leads to decreased hepatic VLDL production and increased LPL activity. This decreases triglycerides by 25-50% and increases HDL by 5-20%
- Fish oil also decrease VLDL production and inhibit synthesis of Apolipoprotein B
Advantages of polysaccharide vaccine for Streptococcus pneumoniae
-23 valent polysaccharide vaccine (Pneumovax) protects against a wider range of serotypes but antibody levels decrease over 5 years.
decreased incidence of replacement strains due to lack of mucosal immunity
Label the different parts of an antibody and what binds where?
A/B
C
D
E
A/B. Site for attachment of antigen in FAB. This is the hypervariable region
C. The two disulfide bonds that hold the heavy chains together
D. C1 must bind FC portions of IgM and IgG in order to activate the classical complement pathway.
E. The Fc binding part of the constant region of the heavy chain. This is the site for attachment to phagocytitic cells. MACROPHAGES. MAST cells can bind the FC portion of IgE
What molecule is involved in mediating the accumulation of pus
Pus consists of a thin protein rich fluid and dead leukocytes, predominently neutrophils
During infection, macrophages and endothelial cells release cytokines such as IL-8 that trigger neutrophils to enter the site of infection via chemostaxis
“Clean up on aisle 8” Neutrophils recruited by IL-8 to clear infections
Mast Cell fun facts
mediates allergic reaction in local tissue
Bind the Fc portion of IgE molecules
IgE crosslinks upon antigen binding –> degranulation –> release of HISTAMINE, HEPARIN, TRYPTASE (can be used as a marker of mast cell activation)
-Chromolyn sodium prevents mast cell deganulation
Mast cell receptor aggregation
The high affinity IgE receptor is found on the surface of mast cells. The IgE receptor binds the FC of the IgE molecule. When the antigen binds to the FAB region of the IgE, multiple IgE antibodies become crosslinked resulting in aggregation of receptors on the mast cell surface
This results in activation of non-receptor tyrosine kinases that triggers an intracellular cascade that results in mast cell and basophil degranulation
IgA protease, who produces it and what the heck does it do?
Produced by Neisseria Gonorrhea, Neisseria Meningitidis, Strep Pneumo, H. Infleunza
This protease cleaves IgA at the hinge region yielding FAB and compromised Fc fragments, thus decreasing its effectiveness
This facilitates bacterial adhearance to mucosal surfaces
Very low immunoglobulin levels is suggestive of what?? and what does it present with in lymph node?
Bruton Agammaglobulinemia
NO B cell maturation in bone marrow. Get buildup of pre-B Cells in bone marrow
Caused by mutation in Bruton Tyrosine Kinase gene
-B lymphocytes normally in the cortex of lymph nodes to form lymphoid follicles
Primary: dense and dormant
Secondary: pale and contain proliferating B-cells
A pt with Bruton would LACK GERMINAL CENTERS where B-cells normally hang out
What muscle passes through the greater sciatic foramen?
-Piriformis muscle: involved in external hip rotation
Where in the cell cycle do these act:
Vinca alkaloids (Vinblastine, Vincristine)
Bleomycin
Doxirubicin
Antimetabolites (5FU, methotrexate, hydroxyurea, 6-mercaptopurine)
Cysplatin, Alkalating Agents
Vinca alkaloids: M phase
Bleomycin: G2 phase
Doxirubicin: G2 phase
Antimetabolites: S Phase
Cysplatin, Alkalating Agents: G0, cell cycle independent
E. Coli virulence factors for:
bacteremia, septic shock
Neonatal Meningitis
Gastroenteritis (bloody)
Gastroenteritis (watery)
UTI
Bacteremia, septic shock –> lipopolysaccharide
Neonatal meningitis –> K1 capsular polysaccharide
Gastroenteritis (bloody) –> Shiga-like toxin
Gastroenteritis (watery) –> Heat labile (cAMP), heat stable (cGMP)enterotoxins
UTI –> P fibriae
Alcohol Withdrawl Progression
mild withdrawal –> seizures –> hallucinations –> DT
Thayer Martin Agar is made up of what and grows what?
Vancomycin –> inhibit gram + bacteria
Polymyxin –> inhibit gram - bacteria
Nystatin –> inhibit yeast
Trimethoprim –> inhibit proteus
Used to isolate....Neiseria
Celiac Disease pathology findings
- Villous Atrophy
- Crypt Hyperplasia
- Intraepithelial lymphocyte infiltration
Dx: anti-tissue trans-glutaminase (anti-TTG), IgA anti-endomysial and is confirmed by tissue biopsy
Tx: with a gluten free diet
Phenotypic Mixing
Occurs with simultaneous infection of a cell with 2 viruses and results in progeny virus that has nucleocapsid components of A and B
*The key here is that there is no exchange of genomic viral genomes and thus in the subsequent generations, A –> A and B –> B
A/B. Phosphoglucomutase (interconverts Glucose-1-phosphate and Glucose-6-phosphate
C. Glucose-6-phosphate dehydrogenase (G6PD)
D. Glucose-6-phosphatase (McArdle)
E. Hexokinase/Glucokinase (hemolytic anemia, rare)
F/G Phosphoglucose Isomerase (hemolytic anemia)
Ionoropic vs metabotropic receptors
Ionotropic: ion channels that open directly upon ligand binding. NICOTINIC…allow immediate influx of ions, such as a nonselective cation channels that open after the binding of ACh.
Metabotropic: use second messengers. MUSCARINIC
idiopathic intracranial hypertension (pseudotumor cerebri)
Increased ICP with no apparent cause
- Young woman of childbearing age w/ daily headache. bilateral symmetrical papilledema, transient vision change, and sx worsen when bending down
- Compression of optic nerve externally that impairs axoplasmic flow within optic nerve
tx: weight loss, acetazolamide, topiramate (seizure)
Propofol distrubution inside the body
- Potentiates GABAa
- A highly lipophilic drug that is used for both induction and maintainence of general anesthesia as well as procedural sedation
- Onset of action is 30 sec, and duration is <10 min. It goes where blood flow is highest (brain) first then goes to areas where blood flow is lower such as fat, muscle tissue
Characteristics of Aortic Regurgitation
Early diastolic murmur
- Signs and symptoms of left heart failure are common
- more advanced cases are a more holosystolic murmur while earlier cases are associated with an early diastolic murmur
- MOST commonly caused by aortic root dilation or bicuspid aortic valve
Germinal Matrix Hemorrhage
- usually results in intraventricular hemorrhage (most common in infants born before 32 weeks gestation and <1500 grams), and almost always occurs in first 5 days postnatal
- The germinal matrix is a highly vascular area where neurons and glial cells migrate out of during development. There are many thin walled vessels in this area that lack the glial fibers and support that other vessels have in the brain
Name the insulin lines
A=Aspart (first)
Why does lactic acidosis cause anion gap metabolic acidosis?
-Lactic acidosis is produced by over production or underexcretion of lactic acid. End organ hypoperfusion in septic shock impairs tissue oxygenation and decreases oxidative phosphorylation leading to a buildup of NADH and shunting of pyruvate to lactate following glycolysis
Pterion fracture (skull)
- This is the spot where the frontal, parietal, temporal and sphenoid bone all join.
- A fracture here is common to cause a middle meningial artery laceration.
The middle meningial artery is a branch off the maxillary artery
-This rupture of an ARTERY –> epidural hematoma, which can lead to increased ICP and cushing reflex, brain herniation, and death
Caudal Regression Syndrome
Pts born with agenesis of the sacrum, and lumbar spine area and experience flaccid paralysis of the legs, and urinary incontinence
-It is frequently related to maternal diabetes that were poorly controlled though there are other factors likely at play
Hemolytic Uremic Syndrome is caused by what?? OK, and what is the actual mechanism that we see?
Caused by E. Coli O157:H7 or Shigella Dystentarie
The Shiga toxin enters the circulation and causes capillary endothelial damage, resulting in platelet activation and microthrombi. This results in thrombocytopenia due to the platelet consumption and schistocytes from the RBCs damaged during the microthrombi resulting in hemolytic anemia
The hemolytic anemia causes decreaed hemoglobin and haptoglobin in the blood as well as increased serum lactate and unconjugated billurubin
Flecainaide
Class 1C antiarrhythmic that is typically used to treat SVT caused by AFIB
These bind to the Na channels responsible for phase 0 depolarization and prolong QRS duration
Class 1C drugs are the slowest to dissociate from the Na channels resulting in a “use dependence” in which their sodium blocking effect is increased when the HR is increased
Dofetilide
- A class III antiarrhythmic that blocks outward potassium current during repolarization. As a result, it increases the QT but NOT the QRS
- This expresses reverse use dependence, the lower the HR, the more effect it has
Central Scotomas
-The macula is a dense bit of cones located 1.5 mm near the retina
Macular lesions impair central vision and result in CENTRAL SCOTOMA
Scotoma = a visual defect surrounded by regular vision
Ataxia Telangectasia mutation
ATM gene responsible for DNA break repair –> cell cycle arrest
-Mutation in this gene is AR and results in cerebellar ataxia, telangectasias and increased risk of sinopulmonary infections
Usually have an IgA deficiency as well
Can see an increased AFP in these pts too
Collagen Synthesis mechanism
Begins with the transcription of collagen in the nucleus. Alpha chains are then synthesized by the RER bound ribosomes and directed into the cisternae of the RER.
Within the RER, proline and Lysine are post-translationally hydroxylated to hydroxylysine and hydroxyproline via prolyl hydroxylase and lysyl hydroxylase.
Defective hydroxylation severely diminishes the amount of collagen secreted by fibroblasts and impairs triple helix production. VITAMIN C is required for HYDROXYLATION
Neuroleptic Malignant Syndrome
life threatening reaction to anti-psychotic medications, which block dopamine receptors in the brain
Presents clinically with diffuse muscle rigidity, high fever, autonomic instability (HTN, tachycardia), and altered sensorium.
CK through the roof as pt has rhabdo
**Think LEAD PIPE RIGIDITY FOR NMS*
*Think hyperreflexia for serotonin syndrome
Tx: discontinue psych med, DANTROLENE (blocks release of Ca from sarcoplasmic reticulum via antagonizing ryanodine receptors)
Trendelenburg Gate is caused by what? and where is the proper spot for an injection (because improper injection technique can cause this problem in the first place…spoiler alert)?
Trendelenburg gate is the dropping of the hip on the contralateral side that is affected. On the affected side, the superior gluteal nerve is affected.
This can be a result of a misplaced injection.
The proper site for an injection is superiorlateral quadrant at a 90 degree entrance is correct.
Injections into superiormedial –> risk superior gluteal
Injections into superiormedial, inferiormedial, inferiorlateral are ALL increased risk of –> sciatic nerve involvement
Why is essential fructosuria a benign condition?
Because hexokinase can take over and convert frucose –> fructose-6-phoshate instead of the fructokinase that normally converts fructose –> fructose-1-phosphate
This is NOT like Hereditary fructose intolerance where you are deficient in Aldolase B. At this point, you have already converted to Fructose-1-phosphate and are STUCK and cannot convert back via hexokinase to Fructose-6-phosphate
PPO vs HMO vs POS for insurance options basic overiview
Explain each layer and which layer specifically is affected by Pernicious anemia and what is pernicious anemia
Pernicious anemia is an autoimmune disorder caused by CD4+ cells against parietal cells in the gastric body and fundus. Over time, this results in atrophic gastritis
A: simple columnar epithelium: secretes mucous
B: Upper glandular layer: where parietal cells secrete gastric acid and intrinsic factor
C: Deeper aspect of gastric glands: This is where Chief cells hang out and secrete pepsinogen
D: Muscularis Mucosa: separates lamina propria from submucosa
E: Submucosa: Where CT is
Biotin (B7) is a cofactor for what enzymatic reactions?
Important for several carboxylase enzymes
Deficiency of biotin can arise from poor diet, excessive raw egg white consumption (due to high levels of biotin-binding avidin in egg whites)
1. Pyruvate carboxylase
2. Acetyl CoA carboxylase
3. Proponyl CoA carboxylase
Present with non-specific symptoms but can include dermatologic changes* mental status change, anorexia
Gingival Hyperplasia is caused by what drug?
Phenytoin! due to increased expression of PDGF
It occurs in 50% of pts who have been on phenytoin for 3-4 months or longer
(also cyclosporine and tacrolimus –> calcineurin inhibitor, as well as CCB)
Label parts of brain…
A. Caudate (A/C are striatum together)
B. Internal Capsule
C. Insular Cortex (limbic system)
D. Putamen
E. Globus Pallidus
(D/E make up Lentiform nucleus)
Mechanism of opiates
-Blocks Mu-receptor via binding to Gi proteins. On presynaptic side: results in closure of voltage-gated calcium channels, reduced calcium influx and thus decreased excitatory NT release.
On post-synaptic side: opens potassium channels and allows for K efflux from cells leading to membrane hyperpolarizaiton
Mood stabilizers in bipolar disorder (4) and their side effects
- Lithium: hypothyroidism, DM, ebstein anomaly, tremor
- Valproate: HEPATOTOXICITY, neural tube defects
- Carbamezapine: AGRANULOCYTOSIS, hyponatremia, NTD
- Lamotrigine: SJS
Enteropeptidase function
activates trypsinogen to trypsin
Trypsin can then go ahead and activate all the other pancreatic enzymes. Trypsin can also begin to break down proteins to oligopeptides and amino acids
Enteropeptidase hangs out in the brush border of the duodenum
Folate pathway and folate deficiency can be shortcutted by what?
Can be shorcutted by thymidine supplementation. This converts dUMP to dTMP
DSM5 Personality disorders
paranoid
schitzoid
schitotypal
antisocial
borderline
histrionic
narcissistic
avoident
dependent
obsessive compulsive
label the parts of the brachial plexus
refamiliarize yourself with the coronary arteries, especially in a R dominant coronary artery person in regards to papillary muscle rupture after an MI
*the posteriormedial papillary muscle is supplied solely by the posterior descending artery unlike the anteriormedial papillary muscle that is supplied by a duel blood supply of the LAD and the L circumflex
papillary muscle rupture is a life-threatening condition that happens 3-5 days after a myocardial infarction and presents with acute mitral regurgitation and pulmonary edema
Immunoflourescence of PSGN shows what?
IF shows granular “lumpy bumpy” (not linear like seen on goodpastures syndrome)
What is actually showing up is C3b, IgG, and IgM in the mesangium and basement membranes
esophageal manometry for achalasia, scleroderma and diffuse esophageal spasm
scleroderma has high pressure at prox esophagus
achalsia is high LES tone
what is lymph node drainage around genital area?
Think about where the testes came from and where the penis goes and what the scrotum is attached to
Scrotum –> superficial inguinal lymph nodes. These lymph nodes drain nearly all cutaneous lymph from the umbilicus to the feet including the external genitalia and anus (up to the dentate line)
THE EXCEPTION is the testes, glans penis, and cutaneous portion of posterior calf
Lymph from the testes –> para-aortic (retroperitoneal)
Glans penis and posterior calf –> deep inguinal lymph nodes
What is this picture of and what is the most likely origin?
48 year old female, weakness shoulder and hip girdle, minor abd pain
The picture is of Dermatomyositis, an autoimmune disease characterized by proximal muscle weakness resembling poliomyolitis.
findings include heliotrope rash, Gottron pappules (pictured on hands)
-This condition may occur alone or as part of a paraneoplastic syndrome from ovarian adenocarcinoma (but can also be lung, colorecta, non-hodgkins)
Anti-jo, Anti-SRP, anti-Mi-2
Osler-Weber-Rendu syndrome
AD inheritence of congenital telangectasias to the skin
ALSO called hereditary hemorrhagic telangectasia
presents with recurrent nose bleeds, skin discolorations
accuracy, precision, reliability, and validity
Reliability (precision) measure of statistical variation. A reliable test is reproducible but not necessarily giving the right answer (bottom two on figure)
Validity (accuracy) the tests ability to measure what it is supposed to measure
What vein is grafted for coronary artery use and where is it taken from?
Great saphenous vein is taken just inferiorlateral to the pubic tubercle
(keep in mind the left internal mammary (thoracic) vein is preferred over the saphenous but often times is already used or not available)
Right near the femoral triangle
Name of gastric bypass and what is a common occurance afterwards due to deficiency of what?
Roux-en-Y Gastric Bypass
Can result in Small Intestinal Bacterial Overgrowth (SIBO)
Enteric bacteria produce Vitamin K and folate, which inhibit proliferation of surrounding pathogenic bacteria and digest unabsorbed dietary sugars
See deficiency in A,D,E,B12,Iron but increase in vit K, folate
Clinical manifestations of Factor V Leiden Mutation
DVT, central vein thrombosis, Cerebral vein thrombosis and recurrent pregnency loss
-Remember that Factor V Leiden produces a mutant factor V that is resistent to inhibition by protein C.
This is the most common cause of hypercoagulability in caucasions
B12 deficiency affects what part of the spinal cord?
- Dorsal column of the spinal cord
- Lateral corticospinal tracts
- Axonal degeneration of peripheral nerves
Called subacute combined degeneration. This is due to abnormal myelin synthesis
Dimpling in breast cancer is caused by what?
Involvement of the suspensory ligaments of the breast (also called Cooper Ligaments)
Entacapone use and mechanism
COMPT inhibitor that increases bioavailability of levodopa by inhibiting its peripheral methylation. If you combine levodopa and Entacapone, you can prolong its duration in the periphery
remember levodopa is the precursor of Dopamine and can cross the BBB
How does shigella infect the body?
Shigella cannot bind all intestinal cells. Instead, shigella can bind microfold (M) cells at the base of the mucosal villi within a Peyers Patch region of the ileal mucosa.
Shigella endocytoses through the M cell and lyses the endosome, multiplies and then spreads laterally inside other epithelial cells
Infectious dose is VERY LOW and it is resisant to gastric acids
Causes bloody diarrhea
Retinal artery occlusion. What is the pathway of the thrombus to get lodged there?
The most common cause is from an atherosclerotic plaque in the internal carotid. This then travels to the opthalmic artery and then to the retinal artery.
Common cause of acute, painless, monocular vision loss
Mechanism behind Huntington Disease
Trinucleotide repeat of CAG on huntington gene that encodes for huntingtin protein. Expansion of the polyglutamine region results in a gain of function mutation.
Autosomal Dominant
Transcriptional repression is one of the mechanisms by which the huntingin protein cuases disease. See increased histone deacetylation, silencing the genes necessary for neuronal survival
20 year hx of alcohol abuse with abd pain, diarrea, memory problems, dermatitis..what is dx…what are common findings and what is deficient and what reactions is it involved in?
Pt has Pellagra…a deficiency of niacin (B3)
Pellagra: Diarrhea, Dementia, Dermatitis (3 D’s of B3)
Niacin is a precursor for NAD and NADP, two important cofactors for many dehydrogenase and reductase enzymes. Often found deficient in ALCOHOLICS
Cofactor for:
1. Isocitrate dehydrogenase
2. Malate dehydrogenase
3. alpha-ketoglutarate dehydrogenase complex
4. pyruvate dehydrogenase
BP 175/68. whats the deal?
This is elevated systolic blood pressure with normal diastolic blood pressure. Called isolated systolic hypertension and is often seen in pts over 60 and is responsible for 60-80% of hypertension in this age group.
Increased arterial stiffness is a common manifestation of aging including increased aortic stiffening
embryologic derivative of the spleen
mesoderm
also muscles, CT, cartilage, CV system, lymphatic system, blood, internal genitalia, kidneys, ureters
MOST gut tissue is endodermal, but the spleen is unique as it is derived from mesenchymal tissue
General functions of the hypothalamic nuclei
ventromedial
lateral
anterior
posterior
arcuate
paraventricular
supraoptic
suprachiasmatic
decreased sensation over 5th finger digit and flattened hypothenar eminence (triceps reflex normal) lesion is where?
Hook of the Hamate
This is an ulnar neuropathy. The nerve enters the wrist between the hook of the hamate and the pisiform bone through guyon’s canal
MOST often the ulnar nerve is injured at the elbow “funny bone”
Process by which DNA is damaged and repaired after UV light exposure
UV exposure creates thimadine dimers –> endonuclease complex recognizes deformed helix –> single strang cleavage on both sides of damage –> damaged DNA is discarded –> DNA polymerase synthesizes replacement –> DNA ligase seals gap
Choosing types of insulin (fast/slow/basal/prandial)
Pain at the front of the neck initilly attributed to illness 1 week ago. Thyroid gland VERY tender with decreased idiodine uptake. ESR 105.
What is it and what is the pathological change?
Subacute granulomatous thyroiditis (de Quervain thyroiditis) typically follows a viral illness. Pts may experience transient hyperthyroid phase that is characterized by elevated T4/T3 suppressed TSH and decreaed iodine. Resolves within 6 months
Pathology: early neutrophilic infiltrate with microabscess formation. This is replaced with lymphocytic infiltrate with macrophages and giant cells
ADH is synthesized where?
paraventricular and supraoptic nuclei of the hypothalamus
Diverticulosis vs Diverticulitis
Diverticulosis: is an outpouching (false diverticulum) caused by increase pressure (pulsion) during bowel movements. This pressure herniates through areas of focal weakness in the muscularis (false diverticula). Most commonly affects the sigmoid colon and can present with painless hematochezia
Diverticulitis: when diverticula become inflammed causing LLQ pain, low grade fever, constipation or diarrhea
D-xylose test
passively absorbed in small intestine. Blood and urine levels decrease with mucosal defect or bacterial overgrowth.
it is a monosaccharide that is abosrbed directly without the action of pancreatic enzymes and can be used to test for brush border absorptive function independent of pancreatic function
This kiddo presents with recurrent skin rashes that come about after eating certain foods. What is it and what is causing it?
This patient has atopic dermatitis (eczema) that can be triggered by various environmental stimuli. Intense pruritis is the hallmark of this disorder and dx cannot be made without it.
Of note, the allergic triad of Asthma, Atopic Dermatitis, and Allergic Rhinitis is very common, esp in kids with a family history
life of a B-cell and what is happening specifically in this photo?
- Precursors proliferate and mature in the BONE MARROW
- Mature B-cells migrate to lymph nodes, where they are exposed to antigens (some B-cells become activated to plasma cells expressing IgM through T-cell independent process)
- B-cells migrate to lymphoid follicles in the lymphoid cortex where they from germinal centers
- Isotype switching then occurs in the germinal centers (this requires CD40 binding to CD40L expressed by activated T-cells
Fetal-Placental aromatase deficiency manifests how?
Both maternal and fetus (if female) virulization
Females will have normal internal genitalia but male external genitalia due to exposure to testosterone (cliteromegaly)
What is it and what is the treatment of this?
Specifically, what treatment activates a nuclear transcription factor?
This is a classic example of psoriasis that is made up of sharply demarcated salmon plaques covered with a losely adherent silvery scale that commonly affects the extensor surfaces.
Tx: topical Vitamin D (in form of calcipotriene or calcitriol). This has been shown to inhibit T-cell proliferation. This binds and inhibits keratinocyte proliferation and stimulates keratinocyte differentiation
hypoketoic hypoglycemia
consistent with a defect in the fatty acid b-odixation in the mitochondria
The most common defect is medium chain acetyl-CoA dehydrogenase deficiency (MCAD)
Most pts are asymptomatic until they experience a significant fasting period
What is this called? And what does it come from?
pt has easy fatigability. hx of gastrectomy due to nonhealing gastric ulcer, unsteady gate
Subacute combined degeneration (B12 deficiency)
-Can occur from pernicious anemia, gastectomy, strict vegan diet
pts also develop atrophic glossitis
What does this lesion represent?
(mass resected from liver)
This is a cavernous hemangioma and is the most common benign liver tumor that presents in adults 30-50 years old.
-Cavernous blood filled vascular spaces of variable sizes lined by a single epithelial layer
BIOPSY CONTRAINDICATED because of risk of HEMORRHAGE
Where does the trigeminal nerve exit from on the brainstem?
The lateral aspect of the midpons at the level of the middle cerebellar peduncle
What does this guy have and what is the inheritance of it? And what are 5 ways it presents?
This is neurofibromatosis type 1 and it is Autosomal Dominant
-This is a mutation on the NF-1 gene on Chr 17
Presentation:
1. Cafe-au-lait spots
2. Neurofibromas
3. Lisch Nodules (hammartomas of iris)
4. Congenital pseudoarthritis
5. Other associated tumors (such as gliomas, astrocytomas, pheochromocytomas)
Pathophys and labs of primary hyperaldosteronism
Characterized by increased sodium reabsorption from the collecting tubule. This creates a negative charge in the lumen pulling H+ and K+ into the lumen. This result in a hypernatremic, hypokalemic, metabolic alkalosis .
The increased H+ in the lumen results in an increase HCO3-/Cl exchanger which promotes bicarb production
The hypernatremia and pedal edema are rarely seen due to aldosterone escape. This is due to increased plama volume leading to increased renal blood flow leading to naturesis which limits the net sodium retention
Fructose 2-6 Biphosphetate does what and what would be the impact if it was blocked?
Helps to regulate PFK-1 (glycolysis) and fructose 1-6 biphosphetase (gluconeogenesis)
Insulin activates PFK2, which then increases PFK1 via fructose 2-6 biphosphetate
Glucagon does the opposite
high concentrations of fructose 2-6 biphosphate inhibit gluconeogenesis leading to decreased conversion of alanine and other gluconeogenic substrates
Diastolic heart failure due to restrictive cardiomyopathy with associated ventricular hypertrophy is indicative of what?
Cardiac amyloidosis due to deposition of AL deposits (Ig light chain)
blue arrow is normal myocardial cells
black arrow is an area of the myocardium infiltrated with amorphous and acellular pink material
walk through the lifecycle of hepatitis B
It is part of the DNA containing Hepadnaviridae and consists of a spherical double layered particle that has a nucleocapsid pore covered by an outer lipoprotein envelope (containing surface HBsAg)
*A partially circular DNA molecule that replicates through reverse transcriptase*
Unique in the fact that it is a DNA virus that replicates via reverse transcription
Most common location for epistaxis
The vascular watershed area of the nasal septum known as Kisselbach plexus
This region has several significant anastamoses:
- septal branch of anterior ethmoidal artery
- lateral nasal branch of sphenopalantine
- septal branch of superior labial artery (branch of the facial artery
Aspiration pneumonia sitting vs laying flat
Sitting –> base of R lower lobe (can be left too but less likely
Laying flat –> posterior segment of the right upper lobe (and superior segment of lower lobe)
Latanaprost use
This is a glaucoma med that is a prostaglandin analog that increases outflow of aqueous humor via uveoscleral outflow
Remember that open angle glaucoma is caused by increased production of aqueous humor and decreased secretion through canal of Schlemm and Uveoscleral outflow tract. It is characterized by increased intraoccular pressure. The symptoms develop over decades and involve loss of peripheral vision
label these parts of the eye
stomach ulcer vs erosion
Gastric erosions: are mucosal defects that do NOT penetrate through the muscularis mucosa. These tend to occur in acute errosive gastropathy that can be caused by NSAIDS, curling, cushing, smoking, ETOH
Gastric ulcers: penetrate through the muscularis mucosa into the submucosa. Causes are NSAIDS (inhibiting prostaglandin synthesis), H.Pylori
Gallstone Ileus
fistula between gallbladder and GI tract –> air in biliary tree –> passage of gallstones into GI tract –> obstruction of iliocecal valve by stone
label this photo
Contraction results in shortening of H and I bands and between Z lines (HIZ shrinkage)
The A band remains the same length (A band is Always the same length)
metabolic effects of human placental lactogen
responsible for gestational diabetes
common pathological causes of gynecomastia
Name 4 different drugs used in Parkinson’s Disease and where they act at
- Entacapone, Tolcapone (COMT inhibitor, keeps levodopa in periphery)
- Carbidopa (prevents DOPA carboxylase from breaking down levadopa)
- Bromocriptine, Pramipexole (Dopamine agonist in CNS)
- Tolcapone in CNS (COMT inhibitor that crosses BBB, keeps Levodopa from being broken down)
Ivabradine mechanism (cardiac drug)
lengthens the slow diastolic depolarization phase by inhibiting the Ifunny channels (mixed Na/K inward current)
Accounts for automaticity of SA and AV nodes. The slope of phase 4 in the SA node determines HR
Cardiac abnormalities associated with:
Down
DiGeorge
Fredreich
Kartaganer
Marfan
Tuberous Sclerosis
Turner
Blood supply to cerebral hemispheres
Important landmarks of the CXR
Mechanism of common antiseizure meds:
phenytoin/carbamezapime
Valproic Acid
Benzoz/Phenobarb
Levetiracetam
Ethosuximide
What is this picture showing and what are some other symptoms that are associated with this disease
This is a Kayser-Fleischer ring and is associated with Wilson’s disease. The rings are caused by the deposition of copper within the basement membrane of the cornea
Wilson’s disease is a rare autosomal resessive disease that affects individuals 5-40 years old. The mutation on chr 13 (ATP7B gene) hinders copper metabolism. Eventually the copper leaks from the injured hepatocytes and enters the circulation where it can deposit in the cornea and the basal ganglia
tx: D-penicillamine
Tourette Disorder
multiple motor and >1 vocal tic (not necessarily concurrent) that lasts > 1 year
The vocal tics can be coughing, grunting, throat clearing, to blurting out inappropriate comments (10-20% of pts)
typically presents in boys 6-15
comorbid ADHD and OCD is common
Anticipation
Pts who receive an abnormal gene from their father tend to develop the disease at a younger age. Common in Huntington, Fredrich Ataxia, Mytonic dystrophy, and Fragile X syndrome
CAG repeats increase during spermatogenesis in the HTT gene on chr 4
The higher number of CAG repeats corresponds to more severe sx
HD is transmitted in AD fashion with COMPLETE PENETRANCE
HA, fever, mental staus change in 9 year old girl with seizures. Speech inappropriate choice of words and difficult to understand. Pt most likely has what?
HSV-1 encephalitis: infection of the oropharynx travels through the olfactory tract or trigeminal nerves to invade the temporal lobes
Pt gets primary oropharynx infection that travels retrograde down the trigeminal nerve. It lives in the trigeminal ganglion. Upon reactivation, it can travel back down anterograde to the face or can continue travel up the nerve into the brain causing encephalitis
accidental exposure to chemicals, pt presents with dizziness, SOB, palpitations, flushed skin, tachnypnic. Pt is given amyl nitrate to inhale. What poisoning does this person have and what is the mechanism behind amyl nitrate
This pt has cyanide poisoning that presents with reddish skin discoloration, tachnypnea, HA, tachycardia, N/V, confusion, weakness
Lab would show lactic acidosis with narrowing of venous PO2 gradient (resulting from inability of tissue to extract O2)
Tx: Inhaled Amyl Nitrate –> oxidises Fe2+ to Fe3+ generating methemeglobin. This is incapable of binding oxygen but can bind cyanide, which will free it from cytochrome oxidase and limit its toxic effects
(can also give thiosulfate and hydroxycoabalin (a precursor for B12))
Side effects of major diuretic classes:
Loops
Thiazides
Potassium Sparing
Carbonic Anhydrase
Osmotic (mannitol)
kidney stones in dehydrated pt due to excess fluid loss from ileostomy (not via urine). What type of stones are these and what is the mechanism behind them?
This is a uric acid stone that often appear rhomboid in shape. They are radiolucent. Risk factors include low pH and low urine volume.
Pts with chronic diarrhea have increased loss of bicarb and are in a state of chronic metabolic acidosis. The kidneys compensate by increasing H secretion into tubule and increasing bicarb reabsorption in collecting ducts. This makes urine acidic and increases conversion of soluble urate salts into insoluble uric acid
Biliary Atresia
partial, complete, or progressive obstruction of extrahepatic bile ducts.
Usually infants appear healthy at birth and then undergo progressive jaundice, dark urine, acholic (pale) stools due to excessive renal excretion of bilirubin and lack of bile
Labs: elevated direct bilirubin (direct =conjugated)
Transesophageal echocardiography (TEE). If at mid esophagus level, what is anterior and what is posterior to the probe
Anterior: Left Atrium
Posterior: Descending Aorta
Lymphatic drainage of rectum above and below dentate line
Above dentate –> internal iliac/ inferior mesenteric
Below dentate –> inguinal
As a general rule of thumb, the lymph drainage follows the blood supply in this area
RBC without central pallor. How present? What disease? and have what additional findings?
Hereditary Spherocytosis: often present with increased indirect billirubin, anemia, reticulocytosis.
The blood smear will show large round cells without any central pallor. This is an AD disease that causes defective membrane binding to due ankryin, spectrin, band 3 mutations
**The most important lab finding is an increase in mean corpuscular hemoglobin concentration MCHC**
Long time smoker presents with lung mass and sodium of 120 and plasma osmo 250 (low). What is initial problem and what is it causing?
The pt has small cell carcinoma of the lung from his smoking habit. This cancer often presents with paraneoplastic syndrome where there is excess ADH produced –> SIADH
This leads to increased water reabosrption by the kidney leading to a temporary subclinical hypervolemia. This shuts down RAAS and stimulates natruetic peptides which then dump Na in urine (naturesis). As a result SIADH pts have normal volume with low sodium = euvolemic hyponatremia
Volume overload sx are NOT seen
sphingomyelinase deficiency. what disease and what is progression of disease?
Neimann-Pick Disease is an AR disease caused by deficiency in sphingomyelinase causing excess spingomyelin. These cells look enlarged and foamy. These lipid-layden foam cells accumulate in the spleen and liver causing hepatosplenomegaly and CNS causing neurodegeration
Death by age 3
Also have cherry red macular spot
High frequency deep brain stimulation for pts with Parkinsons in an attempt to suppress neuronal activity
In Parkinsons there is degeneration of the nigrostriatal pathway. This leads to excessive excitation by the globus pallidus by the subthalamic nucleus, which in turn causes excessive inhibiton of the thalamus. Reduced acvitiy of the thalmus on the cortex results in bradykinesia and ridgitiy
DBS of the globus pallidus internus or subthalamic nuclei inhibits firing of these nuclei, which eventually results in thalamo-cortical disinhibition with improved mobility (think want to take direct leash off of the thalamus and let it fire)
label some features of this photo
what are some common signs of liver cirrhosis
jaundice
Portal Hypertension
esophageal varicies
splenomegaly
ascites
caput medusa
anorectal varices
Hyperestrinism
testicular atrophy
spider angioma
gynecomastia
somatic vs germline mosaicism
somatic –> mutations that arise from mitotic errors AFTER fertilization and propagates through multiple tissues or organs. CANNOT be passed on to next generation. Ex: leukocytes with 40% 46X and 60% XX seen in Turner syndrome
germline –> mutation only in egg or sperm cells. The mutation would be in EVERY cell of the body
Kartagener syndrome triad
- situs invertus
- chronic sinusitis
3. bronchiectasis (photo)
Also have primary ciliary diskinesia –> impaired sperm motility (infertile)
6 classes of drugs that can cause anticholinergic effects (cant see, cant spit, cant pee, cant shit)
- TCA (amitriptyline)
- Antihistamines (diphenhydramine, doxylamine)
- 1st gen antipsychotics (chlorpromazine)
- 2nd gen antipsychotics (clozapine)
- Antiparkinsons drugs (benztropine, trihexyphenidyl)
- Belladonna alkaloids (atropine)
nitrates for CP
direct vascular smooth muscle relaxation resulting in:
- vasidilation of peripheral veins and arteries, predominently vasodilation
- decreased LV wall stress due to decreased preload (decreased LV end-diastolic volume and pressure)
3. modest reduction in afterload due to arterial vasodilation
- mild coronary artery dilation and reduction of coronary vasospasm
foot held in calcaneovalgus position (dorsiflexed and everted)
Often arises from injury to the Tibial nerve at the popliteal fossa can cause weakness of foot plantarflexion. Weakness on foot inversion and toe flexion
*Results in sensory loss over sole of foot too*
AML pt with increasing R sided HA behind his right eye with nasal stuffiness. This is a biopsy of the right maxillary sinus mucosa
Rhizopus species
Tends to affect the paranasal sinuses
Form broad nonseptae hyphae that branch at wide 90 decree angles
Compare to Aspergillus fumigatas BELOW that branch at 45 degrees (V shaped branching
Acute Cholecystitis
Gallstone obstruction of the cystic duct in 90% of cases. Ingestion of fatty food then causes contraction of the gallbladder and results in a colicky pain
US is the best diagnosis of this however nuclear medicine hepatobiliary screening can be an alternative means when US is inconclusive (this is a more precise way to dx acute cholecystitis). Tracer is injected IV and taken up by hepatocytes and dumped into bile. Images are taken throughout
IF you are using an US however, cholecystitis is more likely to show gallbladder wall thickenin, pericholecystic fluid and positive sonographic murphy sign
Niacin can predispose you to?
Gout via decreased renal excretion of uric acid, leading to elevated blood levels and increased risk for acute gouty arthritis
effects of prolonged glucocorticoid therapy on
adipose
adrenal
bone
liver
immune
skeletal
skin
and what organ has the most increase in protein synthesis?
Liver via stimulation of gluconeogenesis and glycogenesis. Both actions lead to an overall increase in liver protein synthesis
Kawasaki Disease findings
Vasculitis of medium sized arteries that affects children <5 years old. Occurs most often in children of Asian descent
Need fever >5 days and 4 of 5 sx below
A serious complication is coronary artery aneurysms
Can treat kids with ASA!!!!
Tibial compartments and their contents (arteries and nerves)
Anterior compartment –> foot extensor muscles, anterior tibial artery, deep peroneal (fibular) nerve
Lateral Compartment –> superficial peroneal nerve
Deep posterior compartment –> tibial nerve, posterior tibial artery and vein, peroneal artery and vein
Superficial posterior compartment –> no vessels, gastroc and soleus
cross-sectional study
simultaneously measures exposures and outcomes (also known as a prevelence study)
has a “snapshot” design that is frequently used in surveys
Hemiballisum effects what part of the brain?
Damage to the subthalamic nucleus can decrease excitation of the globus pallidus internus thereby reducing inhibition of the thalamus and results in hemiballismus (wild, involuntary large amplitude flinging movements involving the proximal limb.
-most commonly occurs in the setting of a lacunar stroke
major side effects of amiodarone:
cardiac
pulm
endocrine
GI/hepatic
occular
dermatologic
neurologic
Remember amiodarone is 40% iodine by weight
amIODarone can cause a lot of alterations in thyroid function
what is the effect of propanolol in hyperthyroidism
hyperadrenderic mainfestations in severe thyrotoxicosis reflect a generalized increased sensitivity to catecholamines
propanolol:
- reduce the pts HR and general feelings of anxiety
- reduces conversion of T4 –> T3 by inhibiting iodothyronine deiodinase
Pathophys of an adult having a patent foramen ovale (PFO)
after birth when the umbilical cord clamps and there is decreased pulmonary vascular resistance, the right atrial pressure lowers and the left atrial pressure rises. This pushes the septum primum against the sptum secundum, closing the foramen ovale.
Incomplete fusion occurs in 25% of adults resulting in a PFO
This usually remains closed as pressure on the left is higher than the right. Conditions such as valsalva release can cause a transient increase in R atrial pressure that can cause a right to left shunt. This is particularily concerning in patients with hypercoagulability
54 year old male generalized weakness and fatiguability and abd discombort. Pallor abd distension massive splenomegaly. Pancytopenia. NO bone marrow can be aspirated
This patient has Hairy Cell Leukemia and the smear will present with lymphocytes with cytoplasmic projections.
This is classically seen in older males and it infiltrates the bone marrow and reticuloendothelial system
Classically causes dry tap on aspiration due to marrow fibrosis. Present with massive splenomegaly
Haemophilus Infleunza B conjugate vaccine (Hib)
vaccines containing the polysaccharide alone are ineffective in children under 2 due to their immature humoral immunity. Therefore, the polysaccharide is conjugated to a carrier protein to amplify the patients humoral response against the polysaccharide through T-cell recruitment.
The carrier protein is from the Tetanus Toxoid protein or outer membrane of Neisseria Meningitidis. Immunity is then increased via T-cell depednent stimulation of B lymphocytes and the production of memory B lymphocytes
Apocrine vs Holocrine vs Merocrine
Apocrine: cells secrete via membrane bound vesicles –> mammary glands
Holocrine: cell lysis releases entire contents of the cytoplasm and cell membrane –> sebaceous glands
Merocrine: cells secrete via exocytosis –> salivary glands, apocrine sweat glands (stupid, I know), eccrine sweat glands
Glanzmann Thromblastenia is defective what and what is this normally a taget of (drug)
AR disorder caused by defective or deficient Gp IIb/IIIa on platelet surfaces that typically present in childhood with mucocutaneous bleeding (increased bleeding time)
Normally, this is a target of Abciximab
label this figure
water deprivation test with desmopressin
Central DI
Nephrogenic DI
Central responds to Desmopressin
Partial nephrogenic partially responds
Complete nephrogenic does not respond at all
when considering the reactions in glycolysis, what is the fastest reaction and what would be the enzyme involved?
Fructose-1-phosphate because it bypasses a few major steps in metabolism allowing for it to be faster
specifically, it bypasses PFK, the rate limiting step of glycolysis
As a result, fructose is metabolized by the liver faster than other monosaccharides and is rapidly cleared from the bloodstream following dietary absorption
solitary mass in the R temporal lobe. What is the visual disturbance
This is destruction of meyers loop, an results in Left homonomous superior quadrantanopia “pie in the sky”
What produced the lesion seen in the picture?
Lysosomal digestion of the tissue.
The brain undergoes liquifactive necrosis
The image shows a secton of the brain with a cystic cavity surrounded by gliosis. Release of lysosomal enzymes from these neurons results in degredation of the tissue in the ischemic region. Phagocytic cells move into the area and and remove the necrotic tissue and leave a cavity and astocytes proliferate and create a glial scar (This whole process of complete digestion of necrotic tissue with formation of a gliosis =liquifactive necrosis)
What is going on in this child’s brain (in the posterior fossa)
This is an Dandy Walker Malformation –> absence or malformation of the cerebellar vermis (red) and cystic dilation of the 4th ventricle (blue) with posterior fossa enlargement
Pts often present with skull enlargement and developmental delay in infancy. Non-communicating hydrocephalus may occur due to atresia of the foramina leusha and magendie resulting in sx of increased ICP
Buprenorphine
Partial opiod agonist that has low efficacy for mu-opioid receptors, but it binds with high affinity (potency) and can prevent binding of other medications.
Essentially it acts as an opiod receptor antagonist in the presence of other opioids and can precipitate WITHDRAWL in opioid pts with chronic pain
Myotonic Dystrophy (Myotonic Type 1 specifically)
AD, CTG trinucleotide repeat expansion in the DMPK gene –> abnormal expression of myotonin protein kinase
shows anticipation
Sx: myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia
“My Tonia, My Testicles, My Toupee, My Ticker”
Cardiac catheter waveforms and avg values for each chamber
Right Atrium: Mean 1-5
Right Ventricle: Sys: 15-30, Dias: 1-6
Pulmonary Artery: Sys: 15-30 Dias 6-12
Left Atrial/PCWP/LVEDP: Mean 6-12
Polyol Pathway (sorbitol breaks down from what to what)
Glucose –> sorbitol (via aldose reudctase) –> fructose (sorbitol dehydrogenase)
Sorbitol accumulates in tissues where sorbitol dehydrogenase is low or in long standing hyperglycemia where there is high levels of sorbitol. Sorbitol cannot cross the cell membrane and is thus trapped in cells.
Sorbitol increases osmotic and oxidative stress and contributes to the pathogenesis of retinopathy
Basically, glucose overwelms the pathway causing intracellular sorbitol accumulation
Paradoxical embolism, what is it and what is the murmur?
Emboli that start in the venous circulation and end up lodged in the arterial circulation via a patent foramen ovale or atrial septal defect (DVT –> Middle Cerebral Atery infarct)
Wide and fixed splitting (no change with respiration) of the second heart sound
This can happen as a transient event such as coughing or during early ventricular systole or defecation
Uretheral injury with pelvic fracture most likey affects what part of the ureter?
The membranous segment of the urethra (right after the prostate) is relatively unsupported by the adjacent tissues and is one of the weakest parts
*This bulbomembranous junction is often injured*
Overdose of methotrexate give what?
Folinic acid (leukovorin)
Can reverse MTX toxicity if given early. It does not require DHFR to be converted to THF and is therfore unaffected by MTX
Leukovorin is given during high dose methotrexate to “rescue” bone marrow and GI and other tissue from MTX toxicity
Additionally, it potentiates 5FU (used in colorectal cancer regimens)
