Key Associations Flashcards
Ureter blood supply
Proximal ureter supplied by renal artery
Distal ureter supplies by superior vesical artery
GLUT2
INSULIN INDEPENDENT
BIDIRECTIONAL- uptake and release of glucose
in liver and kidney
and intestines (glucose out of epithelial cells to portal vein)
Pancreas
Corticospinal tract
Descending, motor
2 neuron system:
- Cortex to anterior horn
- Anterior horn to muscle
Sends signal thru internal capsule
Decussate lower medulla
Aging and the immune system
Immunosenescence is normal age related decline that impairs most aspects of immune function
- loss of telomere length affects rapidly dividing cells —> decreased production of naive B and T cells
- aging associated with chronic low level of inflammation that causes much of remaining naive lymphocyte pool to differentiate into memory lymphocytes against previously encountered antigens
- these changes impair the adaptive immune response to novel antigens (pathogens, vaccinations) and predispose pts to vaccine failure and increased susceptibility to infection
Malignancy with non infectious fever
Hodgkin lymphoma
Pulsation PTH secretion
Stimulates osteoblast proliferation, reduces osteoblast apoptosis, induces increased bone formation
Continuous high levels of PTH lead to excessive release of calcium from bones and increase risk of osteoporosis
FSH in females
Development of ovarian follicle
Stimulates estrogen production from ovaries
Menotropin (human menopausal gonadotropin) therapy mimics FSH and triggers formation of dominant ovarian follicle. When follicle appears mature, exogenous bhCG is administered and stimulates LH surge—> induces ovulation
exogenous bhCG mimics LH surge
Terbinafine
Inhibits synthesis of ergosterol of fungal membrane by inhibiting enzyme squalene epoxidase
Used for tinea corporis (annular scaling plaque with well demarcated raised erythematous borders and central clearing)
Rapidly progressive glomerulonephritis
Severe immunologic injury (anti GBM abs, immune complex deposition)
LM- glomerular crescents
IF- fibrin in crescents
Nephritic syndrome
HPV oncogenicity
Integrates into host genome a d produces E6 and E7 which interact with p53 and Rb
- inhibits cell cycle regulation, evasion of apoptosis—> increased malignant potential
Lipoprotein lipase location
Endothelial cells
Chylomicrons produced by enterocytes from dietary lipids—> chylomicrons secreted in to gut lymphatics—> drain into systemic venous circulation —> LPL on endothelial cells is activated by apolipoprotein C2 on chylomicron—> releases TGs to tissues. Chylomicrons shrink in size dt removal of TGs as FAs and glycerol
TSST1
S aureus exotoxin
Acts as superantigen that binds MHCII and TCR directly, resulting in polyclonal T cell activation and cytokines release —> T CELLS PRODUCE IFN GAMMA, macrophages produce IL1, IL6, TNFalpha
Fever, desquamating rash (resembles sunburn) SHOCK, DIARRHEA, end organ failure
HIGH AST ALT
S aureus also causes SCALDED SKIN SYNDROME in newborn—> EXFOLIATIVE TOXIN, red rash that STARTS AT MOUTH, damage is epidermal, + Nikolsky
Acetyl coA importance
Acetyl coA stimulates gluconeogenesis by increasing activity of pyruvate carboxylase when acetyl coA abundant
Cardiac tumor (adults)
Metastasis, myxomatosis (90% in left atrium; ball valve)
Maintenance dose
[steady state]x(clearance/F)
Cystic fibrosis PFTs
OBSTRUCTIVE PATTERN
- progressive bronchiectasis (weakened dilated bronchioles that collapse early)
- mucus plugging
- Decreased FEV1/FVC
- Increased TLC
- Increased RV
Graves’ disease
Autoimmune hyperthyroidism caused by thyrotropin receptor antibodies
+ thyrotropin receptor antibodies - thyrotropin abs bind and activate TSH receptor causing increased release of thyroid hormone by thyroid gland
TSH receptors also present on fibroblasts, adipocytes, other tissues—> thyroid dermopathy caused by stimulation of FIBROBLASTS and activated T cells, leading to excess production of glycosaminoglycans and adipogenesis —> pretibial myxedema (induration and thickening of skin over shins)
Graves opthalmopathy occurs same manner—> retro orbital tissue expansion pushes globe forward
Myelodysplastic syndrome
Abnormal myeloid progenitor cells
<20% BLASTS
pancytopenia but <20% blasts on bone marrow bx
Can progress to AML
Associated with ENVIRONMENTAL FACTORS:
- Prior radiation
- Chemo
Hyperthyroidism and osteoporosis
Hyperthyroid causes increased bone turnover with NET BONE LOSS
Bone loss driven by T3
- T3 stimulates osteoclast differentiation, increased bone resorption and calcium release
As Ca is released from bones into circulation, PTH suppressed—> decreased reabsorption of Ca in renal tubules and gut—> maintains normal calcium blood levels as bone mineralization is depleted
Renal cell carcinoma
MC site of origin is PCT
Presents as anemia, hematuria, elevated creatinine
Tumor usually well circumscribed and golden because high lipid content
Clear cell carcinoma is MC Type of RCC
Endogenous pyrogens
IL1, IL6, TNFa
Azole MOA
Inhibition of fungal sterol (ergosterol) synthesis by inhibiting cytochrome P450 that converts lanosterol to ergosterol
Mucus, epithelial cells on stool sample indicate
Toxin mediated disease
Watery diarrhea
ETEC Cholera C diff C perfringens Giardia, cryptococcus Rotavirus, norovirus
Carotid body chemoreceptors innervated by
Glossopharyngeal N
Preload also called (2)
LVEDV- volume of blood in LV when FILLED
LVEDP- pressure in LV when filled
Generalized anxiety disorder
CHRONIC MULTIPLE WORRIES, anxiety, tension
Th1 cytokines
Th1 drives CMI- CD8 and macrophages
Macrophages release IL12–> drives Th1 production
Th1 secretes
IL2- Activates B and NK cells, T cell growth factor
IFN gamma- activates Th1 and suppresses Th2, activates more macrophages, express more MHC I and II
TH1 CRITICAL FOR INTRACELLULAR PATHOGENS- esp for Tb and Listeria
Anti hypertensive medications that can cause lipid abnormalities 2
Beta blockers- metoprolol
Thiazides
G6PD deficiency on smear
RBCs with HEINZ BODIES- dark intracellular inclusions that stain with SUPRAVITAL STAIN.
Represent Hb that is denatured/precipitated from oxidative stress
S/s- intravascular and extravascular hemolysis with anemia, reticulocytes, indirect hyperbilirubinemia, low haptoglobin (dt removal of free Hb-haptoglobin complexes)
Wilms tumor
Asymptomatic mass in peds
Associated with WT1 tumor suppressor on chrom 11
Arises from nephroblasts in kidney
Abdominal mass that does not cross midline, HTN, hematuria
Assoc with WAGR (Wilms tumor, aniridia, GU malformation, retardation (motor and intellectual)
Ovarian tumor (benign bilateral)
Serous cystadenoma
Carvidilol moa
Non selective beta blocker With alpha 1 inhibition
Reduces AV conduction and inhibits alpha 1 receptors—> smooth muscle relaxation and vasodilation—> decreases SVR —> reduces preload and afterload
AE- hypotension
CF diagnosis
Elevated sweat Cl levels
Abnormal transepithelial potential difference
Potentiation
Drug B with no therapeutic action enhances therapeutic effect of drug A
Carb idols and levodopa
Saline infusion nonanion gap metabolic acidosis
Excess NaCl increases serum Cl to cause hyperchloremia
Cl and bicarbonate are the only anions, increased Cl causes intracellular shunting of bicarbonate to maintain neutrality
This “loss of bicarbonate” decreases blood pH
Infused NaCl increases ECV, which kidneys respond to by increasing Na excretion—> increased urine Na
TCA cycle isocitrate to alpha ketoglutatrate releases:
NADH and CO2
Beta 2 receptor second messenger
cAMP
beta 2 stimulation —> INCREASED cAMP
- peripheral vasodilation
- bronchodilation
Subdural hematoma
Rupture of bridging veins
Crescent shaped
Primitive atrium
Trabeculated part of LA and RA
IL12
Promotes Th1 development (cell mediated response)
Macrophage secreted
Nitroprusside
Short acting vasodilator (ARTERIES AND VEINS)
- lowers preload and after load
Increases cGMP via direct release of NO
Can cause cyanide toxicity
Alpha 1 receptor second messenger
IP3
- when stimulated, increased IP3 activity—> peripheral vasoconstriction, urethral construction, pupillary dilation
Gram - surface antigens
Outer membrane
LIPOPOLYSACCHARIDE- especially LIPID A component, highly toxic, triggers cytokines release
cAMP signaling hormones (FLAT ChAMPs CHuGG)
FSH LH ACTH TSH CRH hCG ADH V2 MSH PTH CALCITONIN HISTAMINE H2 GLUCAGON GnRH
Neostigmine
Acetylcholinesterase inhibitor used for myasthenia gravis
Pica
Compulsive consumption of non nutritive/ non staple food source
Common in pregnancy, often assoc with iron deficiency, nutritional deficiency
MC- ice, dirt, raw starch (flour, cornstarch)
Initial erythema after superficial burn caused by
Preformed mediators (HISTAMINE) released by mast cells
Deeper burns form blisters dt extravasation thru gaps between damaged venue endothelial cells
PDE5 inhibitor (sildenafil, tadalafil) AEs
Transient bluish discoloration of vision
Monocular vision loss- afferent pupillary defect, decreased visual acuity, optic disc ischemia
Paroxysmal nocturnal hemoglobinuria
Acquire PIGA gene mutation in hematopoietic stem cells—> high complement mediated intravascular hemolysis (at night)
PIGA mutation —> impaired GPI anchor synthesis for DAF/CD55 and CD59/MIRL (protect RBC membrane from complement)
Coombs - hemolytic anemia, pancytopenia, thrombosis (BUDD CHIARI)
Associated with APLASTIC ANEMIA, acute leukemia, pink/red urine in am
CD55/59 - RBCs on flow
Tx- ECULIZUMAB (targets terminal complement protein C5)
CYP450 Inducers
Carbamazepine Phenytoin Phenobarbital Rifampin St John’s Wort
Decreases warfarin effect, decrease in efficacy
Dabigatran reversal
Idarucizumab
Dabigatran is direct inhibitor of thrombin—> oral anticoagulant for stroke and VTE prophylaxis
Thrombin catalyzes conversion of fibrinogen to fibrin in final step of coagulation cascade
Wilms tumor
Asymptomatic mass in peds
Associated with WT1 tumor suppressor on chrom 11
Arises from nephroblasts in kidney
Abdominal mass that does not cross midline, HTN, hematuria
Assoc with WAGR (Wilms tumor, aniridia, GU malformation, retardation (motor and intellectual)
Cocaine withdrawal
Depression with suicidal ideation, fatigue, hypersomnia, hyperphagia, vivid dreams
CD14
Macrophage marker
BINDS LPS (in plasma)
Once bound—> IL1, IL6,IL8, TNF released
Focal nodular hyperplasia
Nonmalignant liver lesion that occurs in YOUNG WOMEN
Lesions appear as small, solitary, PALE NODULES composed of cords of normal
Appearing hepatocytes and a CENTRAL STELLATE SCAR with fibrous septal that surround abnormally large hepatic arterial branches
Usually asymptomatic and incidental finding
ACEi MOA
Block conversion of angiotensin I to angiotensin II—> results in DECREASED aldosterone release and decreased NaK ATPase and Na channel activity in distal segments
- lowers Na
- increases K
- no effect on phos
Bullous impetigo
S aureus exfoliative toxin—> EXFOLATIN
Exfolatin destroys keratinocytes attachments
Cleaves DESMOGLEIN 1 complex
- Desmosome protein
- links keratinocytes together
Affects STRATUM GRANULOSUM (intra epidermal)
von Hippel Lindau disease
Genetic cancer syndrome, AD
Multiple benign, malignancies
VHL tumor suppressor deletion on CHROMOSOME 3
- normally, VHL protein binds HYPOXIA INDUCIBLE FACTOR and tags it for ubiqutination—> post translational modification—> adds ubiquitin to proteins to be degraded in proteasome
In VHL, ubiquitination will not occur—> cells will behave as if they are hypoxic—> blood vessel growth
MULTIPLE HEMANGIOBLASTOMAS
- occurs in cerebellum, spinal cord, retina
RENAL CELL CARCINOMAS (bilateral)
PHEOCHROMOCYTOMAS
VHL needs 2 hits to devo malignancy—> similar to retinoblastoma, Li Fraumeni, FAP
Overflow incontinence
Impaired detrusor contractility, bladder outlet obstruction
Incomplete emptying and persistent involuntary dribbling
PVR HIGH
Phase I, II, III, IV clinical trials
I- PKs, PDs, safety profile in small number of people
II- drug efficacy in small number of people
III- safety and efficacy of new treatment compared to standard
IV- adverse effects over time
Decompensated HF LVED pressure and RA pressure
- INCREASED LVED pressure- decreased CO
- INCREASED RA pressure- RAP represents central venous pressure and elevation is indicative of volume overload and possible RHF. RHF MC occurs dt LHF
Tregs
CD3, CD4, CD25, FOXP3 identification markers
Produce anti inflamm- IL10 aND TGFb
Carotid artery pharyngeal arch
Third pharyngeal arch
GPCR and AC pathway
GPCR—> adenylyl cyclase converts ATP to cAMP—> cAMP activates protein kinase A
Chronic hepatitis B histology
Ground glass hepatocytes and central balloon degeneration
Clear cell carcinoma of vagina
DES exposure in utero
Raloxifene MOA
SERM
DOES NOT INCREASE RISK OF ENDOMETRIAL CANCER
Agonist effects on bone
Antagonist effects on uterine and breast tissue
Social anxiety disorder
Anxiety restricted to social and performance situation
FEAR OF SCRUTINY and embarrassment
Posteromedial papillary muscle blood supply (1)
RCA
Inferior infarction can lead to rupture of PM papillary muscle
- severe MR
- acute HF
6MP and Azathioprine
Chemo agent
Disrupts purine salvage pathway and de novo synthesis
Mimics hypoxanthine (IMP) and guanine (GMP) —> added to PRPP creates thioinosinic acid
LESS IMP/AMP/GMP
CAUTION WITH ALLOPURINOL- may boost 6MP effects and toxicity
CD8 T cells
Cytotoxic T cells
Kill viral infected cells and tumor cells
Cardiac tamponade
Restriction of diastolic filling of the right heart, with engorgement and decreased inspiration collapse of IVC
PULSUS PARADOXUS (>10mmHg drop in SBP during inspiration
Electrical alternans on EKG
Equal diastolic filling pressures in all 4 chambers —> chambers cannot relax
Becks triad- hypotension, JVD, distant heart sounds
MYC proto oncogene
Transcription factor
Burkitt lymphoma
Chronic active hepatitis
Jaundiced, elevated liver enzymes, elevated HBsAg and anti HBc IgG indicates chronic active hepatitis B infection
Histology: dense lymphocytic inflammation, piecemeal (peripheral) necrosis, GROUND GLASS HEPATOCYTES (granular eosinophilic cytoplasm)
Sulfonamides MOA and AE
Inhibit dihydropteroate synthase —> inhibits folate synthesis
Resistance- altered enzyme, decreased uptake, high PABA synthesis
VERY HIGH AMOUNT OF HSRs and hemolysis in G6PD
Splenorenal ligament
Located between left kidney and spleen
Contains tail of pancreas and splenic artery (branch of celiac trunk)
Cholesteatomas
Collections of squamous cell debris that form pearly mass behind tympanic membrane in middle ear
Can be congenital or acquired (following infection, trauma, surgery of middle ear)
Can cause hearing loss dt erosion into auditory ossicles
Why is there a small drop in PO2 when blood enters LA from pulmonary veins?
Dt mixing of deoxygenated blood with oxygenated blood from pulmonary veins
Deoxygenated blood comes from:
1. The bronchial arteries carry blood to the bronchi and bronchioles and, together with the pulmonary artery, form the dual blood supply to the lungs. The bronchial veins return only a portion of this blood to the right heart via azygous/hemi azygous; most of the blood supplied by the bronchial arteries returns to the left heart via pulmonary veins
- Small cardiac (thebesian) veins that drain into the LA and ventricle contribute to normal anatomic shunting
Melanoma gene mutations
- BRAF mutation
- proto oncogene
- triggers cell proliferation with RAS activation
- V600E mutation—> treatable with BRAF inhibitors (VEMURAFENIB, DABRAFENIB)
Duchenne muscular dystrophy inheritance
X LINKED RECESSIVE
Same as Hemophilia A
Non Hodgkin lymphoma
Multiple peripheral sites
Non contiguous spread
Extranodal involvement- gi (thickened bowel wall), skin
WALDEYERS RING- lymphoid tissue in pharynx, enlargement of Waldeyers ring common in non Hodgkin lymphoma, NOT Hodgkin lymphoma
cGMP hormone signaling
Vasodilation and diuresis
BNP
ANP
EDRF (NO)
PD1 and PDL1 blockade
The binding of programmed cell death protein PD1 to one of its ligands PDL1 Dow regulates the immune response by inhibiting cytotoxic T cells
Many cancers evade immunodetection by increasing expression of PDL1 on their surface.
Mab against PD1 upregulate the T cell response and promote tumor apoptosis
PD1 mab- pembrolizumab, nivolumab
PDL1 mab- atezolizumab
DCML
Ascending tract
Senses pressure, vibration, fine touch, PROPRIOCEPTION
Decussates at medulla
Hemochromatosis
Multiple blood transfusions or hereditary HFE mutation (can result in HF, bronze diabetes, and high risk HCC)
Partial mole
One set of maternal DNA and 2 sets of paternal DNA—> 69XXY
Trophoblastic proliferation is limited
Normal uterine size, slight elevation in hCG, PRESENCE OF FETAL TISSUE, partial hydronic degeneration
Less likely to transform to choriocarcinoma
BRCA1/2 tumor suppressor
DNA repair genes
Breast
Ovarian
Pancreatic cancers
Aminoglycoside abx MOA
Gentamicin, tobramycin
Bind 30S ribosomal subunit and inhibit protein synthesis
RISK OF ACUTE KIDNEY INJURY
- acute tubular necrosis (focal tubular epithelial necrosis with granular casts that obstruct tubular lumen and lead to rupture of basement membrane)
- electrolyte wasting, Franconia syndrome, loss of concentrating capacity with polyuria
Mild proteinuria with granular or hyaline casts
Maintenance dose
[steady state]x(clearance/F)
Cyclosporine MOA and AE
Calcineurin inhibitor
Blocks T cell activation by PREVENTING TRANSCRIPTION OF IL2
AE- NEPHROTOXIC (vasoconstricts afferent and efferent, GINGIVAL HYPERPLASIA, HIRSUTISM
Treat secondary HTN with DILTIAZEM
Small cell carcinoma of lung
Associated with smoking, grows rapidly, disseminates early
Located CENTRALLY, along bronchial airways, GREY TAN WHITE MASS
Tumor composed of small round or polygonal cells and associated with MYCL oncogene
Small cell lung cancer can mimic lymphoma therefore MUST ensure tumor DOES NOT STAIN FOR LEUKOCYTE COMMON ANTIGEN (LCA)
- can exhibit crush cell artifact
Tumor derived from bronchial NEUROENDOCRINE CELLS
IHC: NSE and CHROMAGRANIN confirm neuroendocrine origin.
Cytokeratin confirms epithelial cell differentiation
Paraneoplastic syndromes- SIADH, ACTH secretion
Emphysema
Destruction of airspace walls creates enlarged cystic spaces in place of normal lung tissue
Functional consequences of tissue loss:
- decreased elastic recoil—> increased lung compliance. TLC increases and patients may develop barrel chest
- decreased mechanical tethering of airways-> airway collapse and air trapping, which increases RV
- airway collapse and obstruction reduces FEV1, FEV1/FVC ratio
- decreased alveolar surface area—> decreased gas exchange. Manifests as a reduced lung diffusing capacity for carbon dioxide (DLCO)
When emphysema predominates, patients tend to hyperventilate and use accessory muscles, giving a pink complexion (pink puffer)
Contraindicated osteoporosis medication in patients with esophageal dysmotility
Bisphosphonates
- irritate GI lining
- contraindicated in patients with GI motility disorders (achalasia)
- other side effects include osteonecrosis of jaw, femur fx, hypocalcemia
Pseudoachalasia
Associated with esophageal malignancy abs produces symptoms of solid and liquid dysphagia, regurgitation, chest pain, weight loss
Findings on manometry include elevated LES pressure and absence of peristalsis
Pseudoachalasia can be differentiated from achalasia by duration and progression of symptoms (pseudoachalasia more rapid than achalasia), asymmetrical esophageal wall thickening, inability to pass endoscope thru LES, presence of enlarged supraclavicular LNs
Charcot Marie Tooth disease
Hereditary peripheral neuropathy caused by mutations in genes coding for peripheral nerve axonal or myelin proteins
Present in adolescence with progressive, symmetric distal muscle atrophy and weakness
ANKLE SPRAINS, difficulty with exercise
Muscle wasting in distal LE, sensory loss, areflexia, PES CAVUS (high arch), hammer toes
Main respiratory drive in healthy people
Increase in PaCO2
- stimulates central chemoreceptors and triggers increased ventilation
Lectin complement pathway
Lectin pattern recognition receptor binding
Host pattern recognition receptors bind to carbohydrates that are produced only by pathogens. Binding generates cleavage of C4 and C2 to C3 without C1
Follicular lymphoma
Abundance of follicles on LN bx
CD19 and CD20 +
t(14;18)—> overexpression of BCL2, blocks apoptosis, uncontrolled B cell growth
- germinal center B cells usually lack BCL2–> when overexpressed—> uncontrolled B cell growth
Older patients (65yo)
Usually indolent course, CAN CONVERT TO DIFFUSE LARGE B CELL LYMPHOMA (DLBCL)—> poor prognosis
Ethambutol MOA
Inhibits arabinosyl transferase
May cause optic neuropathy
Bosentan
Pulmonary HTN drug
Endothelin receptor anatagonist
Competitively antagonizes endothelin1 receptors—> lowered pulmonary vascular resistance
AE: hepatotoxic
Mycosis fungoides
Patches, plaques, tumors
Varying size, shape
Indolent
“Bathing trunk” distribution
Dx: skin bx with lymphoid cells, ATYPICAL LYMPHOCYTES WITH CEREBRIFORM NUCLEI AND PAUTRIER MICROABSCESSES (epidermal aggregates)
3 diseases caused by Bartonella henslae
- Cat scratch disease
- low fever, tender, proximal regional LAD, self limited - Bacillary angiomatosis
- immunocompromised pts. Red purple papular lesions, can be found in viscera, can be fatal if not treated - Culture negative endocarditis
Nitrates
Vasodilator VEINS
- reduces PRELOAD
Vasodilates by increased NO in vascular smooth muscle—> increase cGMP and smooth muscle relaxation
CONTRAINDICATED IN RV MI, HYPERTROPHIC CARDIOMYOPATHY, concurrent PDE5 inhibitor use
Give with beta blocker to avoid reflex tachy, associated with Monday disease (tolerance during the week, washout during weekend, HA, tachycardia, dizzy upon re exposure)
Familial Mediterranean fever
Rate hereditary dx
Inflammatory disease, recurrent episodes of fever and inflammatory pain
Involves NEUTROPHILS
Serosal inflammation- abd pain, pericarditis
Secondary (AA) amyloidosis MAJOR CAUSE OF DEATH
tx w COLCHICINE (inhibits neutrophils)
Phentolamine
Reversible alpha blocker
Given to pts on MAOi who eat tyramine rich food and for severe cocaine induced HTN
AE- orthostatic hypotension, reflex tachycardia
Acute myelogenous leukemia
Myeloblast malignancy
Adult males
S/s- bone marrow suppression
- myeloblasts accumulate in marrow, suppress cell growth
- anemia, fatigue, weakness, pallor
- thrombocytopenia (bleeding gums)
Peripheral smear- anemia, thrombocytopenia, BLASTS, MYELOPEROXIDASE (MPO) +, AUER RODS
Cluster B (dramatic/erratic) 4
- Antisocial- disregard and violation of others rights
- Borderline- chaotic relationships, abandonment fears, labile, mood, impulsivity, inner emptiness, self harm
- Histrionic- superficial, theatrical, attention seeking
- Narcissistic- grandiosity, lack of empathy
Multiple myeloma
Plasma cell disorder characterized by infiltration of bone marrow by neoplastic cells
Bone marrow shows abnormal plasma cells containing immunoglobulin rich Russell bodies
S/s: bone pain, pathological fractures, anemia, increased infections, hypercalcemia, renal failure
Punched out lytic lesions on XR
BENCE JONES PROTEINS IN URINE dt kappa or lambda light chain excretion
Monoclonal IgG spike typically on protein electrophoresis
Rocky Mountain spotted fever
Tick borne illness from
American dog tick
Illness dt Rickettsia rickettsi (weakly GN obligate intracellular organism with affinity for vascular endothelial cells)
Patients have non specific symptoms (fever, malaise, myalgia) followed by rash that begins at ankles and spreads to body and PALMS AND SOLES
Treat with DOXYCYCLINE
Initial step in atherosclerosis
Endothelial damage from external factors- HTN, smoking, advanced fly action of end products which leads to inflammation, adhesiveness, and invasion of SMCs into tunica intima
Intraductal papilloma
MC cause of pathological (bloody, serosanguinous, unilateral w or wo palpable masses abs skin changes)
Classically presents as unilateral bloody nipple discharge with NO breast masses, skin changes, or axillary LAD
Most cases are BENIGN
BX: epithelial and myoepithelial cells lining around a fibrovascular core forming papillae within duct or cyst wall
Bloody discharge is from twisting of the vascular stalk of papilloma in duct
Antibody dependent cellular toxicity
Adaptive and innate immune systems work together to kill pathogen
Antibodies coat pathogen/cell—> pathogen destroyed by immune cells in non phagocytotic process
Examples: NK cells and eosinophils
Ie. IgG abs coat target pathogen—> NK cell CD16 binds Fc of IgG and NK cell degranulates
Triptans and migraines
Migraine pathogenesis includes genetic predisposition to increased cerebral excitability, allowing wave of cortical spreading depression to propagate across cerebral cortex —> aura and abnormal activation of trigeminal afferents (which extend into meninges and intracranial vasculature)
This activation leads to release of CALCITONIN GENE RELATED PEPTIDE (CGRP), a neuropeptide involved in pain transmission
CGRP also causes local vasodilation and increases neurogenic inflammation—> further sensitized trigeminal afferents and increases pain
Triptans- 5-HT1B/1D receptor agonists that cause:
Vasoconstriction of (dilated) cranial and basilar arteries
Inhibition of trigeminal nerve nociception
Inhibition of vasoactive peptide secretion
Most effective if taken at the onset of headache
Immune surveillance
Process by which cytotoxic lymphocytes and NK cells can recognize NEOPLASTIC cells by expression of tumor antigens or lack of expression of self antigens (MHC I)
Primary ciliary dyskinesia
Dx by LOW nasal nitric oxide levels
Main determinant of TOF severity of cyanosis
RV outflow obstruction
RV obstruction dt central pulmonary valve stenosis and hypoplasia determines severity of cyanosis and intensity of systolic murmur
Higher degree of RV outflow obstruction, the more unoxygenated blood bypasses pulmonary circulation and shunts straight thru VSD to LV
Schuffner dots
Only found in P. Vivax or P. Ovale
Appear as multiple brick red dots (punctuate granulations)
Increased cAMP receptors (2)
Beta 1 (increased cardiac contractility and HR, increased renin release from JG cells)
Beta 2 (peripheral vasodilation and bronchodilation)
Tricyclic MOA
Block reuptake of NE and epi—> increases levels of neurotransmitters in synaptic space
Amitryptiline, nortryptiline, imipramine
POSSESS STRONG ANTIMUSCARINIC EFFECTS- dry mouth, tachycardia, urinary retention and sedation
Orthostatic hypotension, QT PROLONGATION, TORSADES DE POINTES, AV BLOCK
Sex hormones in aging male
Slow decline in gonadal testosterone production with lower total and free testosterone levels
Compensatory rise in LH
Increased hepatic synthesis and higher levels of sex hormone binding globulin
Endothelins
Potent vasoconstrictors
Proteins released by endothelial cells near site of endothelial damage
Endothelin receptor blockers used in pulmonary HTN to lower pulmonary vasoconstriction.
HER2
Tyrosine kinase receptor over expressed in 20% breast cancers
Protooncogene
Overexpression associated with more aggressive clinical course and worse prognosis
Targeted directly by TRASTUZUMAB
How many days is luteal phase
14
Luteal phase is time between ovulation and onset of menstruation.
Luteal phase is constant 14 days dt life span of corpus luteum
Follicular phase (beginning of cycle) is variable
Fenoldopam
D1 sympathomimetic
LOWER BP (vasodilation) Increased HR, CO
Used in postop HTN, HTN crisis
Vasodilator (coronary, peripheral, RENAL, splanchnic)
PROMOTES NATRIURESIS
Can cause hypotension and tachycardia
Arginase deficiency
Progressive b/l spastic stiffness, abnormal movements, growth delay, elevated arginine levels
Arginase normally produces urea and ornithine from arginine
Mild or no hyperammonemia
Treatment- arginine free diet, low protein
Wiskott Aldrich syndrome
Mutation in WAS gene, leukocytes and platelets unable to reorganize actin cytoskeleton —> defective antigen presentation
X LINKED RECESSIVE
Thrombocytopenia
Eczema
Recurrent (pyrogenic) infections
LOW IgG, IgM
HIGH IGE AND IGA
How does efferent arteriole construction affect GFR and filter fraction (FF)
Increases GFR- Efferent constriction causes significant increase in glomerular capillary hydrostatic pressure because of reduction in renal blood outflow. This also reduces RPF
Increased FF - increased GFR + decreased RPF. Decreased RPF allows slower capillary flow and more time for filtration of plasma across glomerular membrane
As efferent arteriolar constriction increases—> GFR will decrease dt flow mediated rise in oncotic pressure in glomerular capillaries
Secondary hyperparathyroidism
Hypocalcemia dt CKD
Ethosuximide MOA
Blocks thalamic T type Ca channels
First line absence seizures
VHL tumor suppressor
Ubiquitin ligase, inhibits hypoxia inducible factor 1a
Renal cell carcinoma
von Hippel Landau syndrome
Invasive ductal cell carcinoma
MC type of breast cancer
Affects both genders
Histology shows MALIGNANT GLANDS, ABSENT MYOEPITHELIAL CELLS, surrounded by STROMAL DESMOPLASIA
Ectopic pregnancy medical treatment
Methotrexate
- folic acid antagonist —> inhibits DNA synthesis and cell reproduction—> preferential destruction of actively proliferating cells ie fetal cells and trophoblasts
Vitamin B6 (pyradoxine)
Transamination (AST, ALT)
Decarboxylation reactions
Glycogen phosphorylase
Synthesis of glutathione, cystathione, heme, niacin, histamine, neurotransmitters
Deficiency- sideroblastic anemia, convulsions, hyper irritability, peripheral neuropathy
Deficiency inducible by INH and OCP
Cluster headaches
Trigeminal autonomic cephalagia
Behind one eye, excruciating sharp and stead pain (ice pick)
Ipsilateral sweating, facial flushing, nasal congestion or rhinorrhea, pupillary changes, lacrimation, ptosis, miosis
Tx with triptans and verapamil
Gram + surface antigens
Cell wall and membrane (thick peptidoglycan)
LIPOTEICHOIC ACID (LTA)
Acetaminophen overdose liver histology
Hepatic inflammation
Necrosis with neutrophilic infiltration
Pt will have vomiting, confusion, fever
Trimethoprim and pyramethamine
Inhibits bacterial dihydrofolate reductase
CAN CAUSE BONE MARROE SUPPRESSION (leucovorin rescue)
McArdle disease
Muscle glycogen phosphorylase deficiency (myophosphorylase deficiency)
Muscle cramps, weakness with exercise, myoglobinuria, no lactate rise during strenuous exercise
Chronic myelogenous leukemia
Fatigue, fever, splenomegaly
Peripheral smear shows many GRANULOCYTES, varying stages of maturation
BCR-ABL gene from t(9;22) translocation —> unregulated tyrosine kinase activity
Tx: IMATINIB - tyrosine kinase inhibitor
Mallory bodies
Condensed cytoskeleton proteins
Eosinophilic cytoplasmic inclusions that do not stain with PAS
Seen in alcoholic hepatitis
Metanephros (metanephric blastema) gives rise to (5)
- Glomeruli
- Bowmans capsule
- Proximal tubules
- Loop of henle
- DCT
Retinoblastoma
Rare childhood eye malignancy
Mutations in RB1 gene—> codes for Rb protein, abnormal Rb—> unregulated cell growth via E2F
Rb holds E2F back and controls cell growth
Inherited forms- child born with 1 mutated Rb, initially child heterozygous—> loss of heterozygosity—> cancer
Chocolate agar properties
Grows Haemophilus influenzae
Contains NAD (factor V) and hemin (factor X)
Classic scenario- H influenzae will grow on plate with Staph aureus because S aureus is beta hemolytic and will lyse RBCs and release NAD and hemin for H influenzae to grow
Succinate to fumarate releases
FADH2
Suspensory ligament of ovary (infundibulopelvic ligament) contents
Ovarian artery
Ovarian vein
Lymphatics
Nerves
Ovarian artery is major blood supply for ovary
Therefore suspensory ligament must be located during oophorectomy to prevent bleeding
Epidural hematoma cause
Head trauma to temporal bone—> ruptures middle meningeal artery
Characteristic lucid interval with loss of consciousness and coma and deterioration
Dengue fever complication
Vascular/plasma leakage syndrome
- dt increased capillary permeability during infection
S/s: high fever (break bone fever), RETRO ORBITAL EYE PAIN, n/v, mucosal bleeding, fluid accumulation
To decrease preload
Remove volume
Raise HR
Pool blood in veins—>MOA of nitrates
Friedrichs ataxia
AR
Tri nucleotide repeat within FRATAXIN gene
Assoc with kyphoscoliosis, pes cavus, ataxia, nystagmus, dysarthria, HYPERTROPHIC CARDIOMYOPATHY
Virchow triad (high risk of thrombosis)
Hypercoagability
Endothelial damage
Blood stasis
Dapsone
Competes with para aminobenzoic acid (PABA)
Inhibits dihydropteroate synthetase
Disrupts folic acid pathway
Used for Pneumocystis jiroveci and Mycobacteria leprae (leprosy)
Causes hemolysis in G6PD
can cause agranulocytosis
Rheumatic fever JONES criteria
Joint pain (migratory polyarthritis) Carditis Nodules (subQ) Erythema marginatum (evanescence rash with ring margin) Sydenham chorea
Neutrophil crawling (tight binding)
Neutrophils express integrins that bind ICAM on endothelial cells
DCML
Vibration
Propioception
Oligodendrocytes
Myelinates CNS axons
Most common glial cell in white matter
Destroyed in MS
4 carcinomas Route Hematogenously
Follicular thyroid
Choriocarcinoma
Renal cell carcinoma
Hepatocellular carcinoma
Primary sclerosis cholangitis
Autoimmune
Inflammation, FIBROSIS, STRICTURES, in biliary tree—> involves INTRA AND EXTRA HEPATIC BILE DUCTS
STRONGLY ASSOC WITH ULCERATIVE COLITIS
Cholestasis, ELEVATED IGM, + P ANCA
Histology- ONION SKINNING BILE DUCT FINROSIS and strictures alternating with dilations—> “beading”
HIGH RISK OF CHOLANGIOCARCINOMA (bile duct cancer)
Class IC antiarrythmics
Flecainide, propafenone
Blocks voltage gated Na channels in high use dependence manner - binds Na channel in open/inactivated states —> class IC dissociates SLOWLY from receptor which allows their blocking effects to accumulate over multiple cardiac cycles
Greater heart blockade at higher heart rates—> good for terminating tachyarrhythmias
Sodium channel binding strength IC>IA>IB
Anemia of chronic disease
Inflammation (high IL6)—> high HEPCIDIN (released by liver, binds ferroportin on intestinal mucosal cells and macrophages, thus inhibiting iron transport)—> decreased release of iron from macrophages and decreased iron absorption from gut
Mild anemia
Lack of available iron—> trapped in storage form
KEY MEDIATOR IS HEPCIDIN
Low iron, low TINC, HIGH ferritin (age trapped in cells)
Volume of distribution equation
Vd = amnt injected/[drug]
Vd of plasma protein bound drugs can be altered by hypoalbuminemia (kidney/ liver dx)
IgA nephropathy
Deposition of IgA containing complexes
LM- mesangial hypercellularity
IF- IgA in mesangium
Renal tumor
Renal cell carcinoma: associated with VHL and cigarette smoking; paraneoplastic syndromes (EPO, renin, PTHrP, ACTH)
Sites of atherosclerosis
Abdominal aorta > coronary arteries > popliteal artery > carotid arteries
Sheehan syndrome
Panhypopituitarisn dt ischemic necrosis of pituitary gland
During pregnancy, pituitary enlarges dt estrogen induced hyperplasia of the lactotrophs, but the blood supply does not increase proportionally
As a result, enlarged pituitary is vulnerable to ischemia in case of systemic hypotension dt peripartum hemorrhage
Toxins inhibiting phagocytosis
Bordatella pertussis- pertussis toxin
INACTIVATES Gi—> AC activation—> high cAMP and impaired neutrophil recruitment
Rough ER
Studded with ribosomes
Involved in transfer of proteins to cell membrane and extra cellular space
Well developed in protein secreting cells
Pentose phosphate pathway
Generates NADPH and ribose 5 phosphate
Glucose 6 phosphate dehydrogenase catalyze the initial and rate limiting step—> deficiency of G6PD causes hemolytic anemia dt inability to generate NADPH
Transketolase inter concerts ribose 5 phosphate (nucleotide precursor) and glucose 6 phosphate (glycolysis intermediate)
Parinaud syndrome
Caused by PINEAL TUMOR compression SUPERIOR COLLICULI and PRETECTAL AREA of DORSAL MIDBRAIN (region containing vertical gaze center)—> vertical palsy
- vertical gaze defects
- noncommunicating hydrocephalus dt compression of cerebral aqueduct
- near light dissociation (large pupils that do not react to light but react to near far accommodation (accommodate but do not react)
Glucose 6 phosphate dehydrogenase deficiency
Cannot convert glucose 6 phosphate to 6 phosphogluconate
G6PD is rate limiting step of PPP
Schizoaffective disorder
Mania, delusions, hallucination occurring in the absence of major mood episode
Life time history of at least 2 weeks of psychotic symptoms in the absence of mood episode
Renal ammoniagenesis
Acidosis in body stimulates renal tubular epithelial cells to metabolize glutamine to glutamate, which generates ammonium that is excreted in urine and bicarbonate that is reabsorbed into blood
This process is responsible for majority of renal acid excretion in chronic acidotic states
Warthin tumor
Benign salivary tumor that has strong association with cigarette smoking
Usually bilateral, slow growing
Histologically characterized by cystic spaces lined by oncocytic cells abs dense lymphoid stroma with germinal centers
Patella fracture
Caused by direct impact to anterior knee
Acutely swollen knee
Focal patellar tenderness
INABILITY TO EXTEND KNEE AGAINST GRAVITY
Palpable gap in extensor mechanism
G6PD deficiency inheritance
X linked recessive
Males affected, females carriers
Viral infection associated with Paget disease
Paramyxovirus infection of osteoclasts
Clonidine MOA
Anti hypertensive
Stimulates central alpha 2 adrenergic receptors —> decreased presynaptic release of NE and decrease in sympathetic outflow
Prevents normal baro receptor mediated increase in PVR and HR during standing and causes orthostatic syncope
African malaria Plasmodium
P. Falciparum
Klinefelter syndrome
47XXY
Dx at puberty
- Primary testicular failure dt hyalinization and fibrosis of seminiferous tubules—> small firm testes and azoospermia. Leydig cell dysfunction occurs and leads to testosterone deficiency, LH and FSH INCREASED dt gonadal failure
- Euchanoid body dt no testosterone
- MR
Hypoparathyroidism
Accidental excision during thyroidectomy
Tetrodotoxin
Neurotoxin that blocks Na channels—> inhibits signaling
Found in Japanese puffer fish
CREST autoab
anticentromere antibodies
Calcinosis cutis Raynaud phenomenon Esophageal dysmotility- from esophageal sclerosis Sclerodactylyl Telangiectasias
Imiquimod
Topical immunomodulatory drug that treats derm dx associated with abnormal cell proliferation
- HPV, basal cell carcinoma, actinic keratosis
Works by activation of toll like receptor 7–> upregulates proinflammatory transcription factor NFkB —> increased cytokines production and enhanced immune mediated killing of aberrant cells
Also induces apoptosis- via inhibition of bcl2 (increased caspases)
- inhibits angiogenesis
Neurocysterocosis
Taenia solium (pork tapeworm) ingestion
Causes multiple brain lesions
- cystic lesions
- seizures
Tx praziquantel
Classical pathway of complement activation
Antibody- antigen binding
C1 complex forms on arc portion of IgM and IgG that’s bound to antigen
C1 complex cleaves C4 and C2 into C3 convertase
MC cause of complement deficiency is autoantibodies (which activates classical complement system after binding host antigens)—> low C4 and C3 leveler and normal Factor B, CH50 levels will also be low (measures functional activity of classical pathway). This pattern common in SLE.
CD4 T cells
Helper T cells
Produce cytokines
Activate other cells
DIRECT IMMUNE RESPONSE
Trastuzumab
mab against HER2 tyrosine kinase receptor
Kills cancer cells by ANTIBODY DEPENDENT CELL MEDIATED CYTOXICITY
- cell tagged by abs, effector cell (NK cells) binds to Fc portion of abs and releases toxic contents that kill cells—> targeted killing
Assoc with cardiotoxicity (NOT dose dependent, reversible when drug stopped), no necrosis on heart bx
ARB MOA
Block angiotensin II type 1 receptors, inhibiting effects of angiotensin II
Results in arterial vasodilation and decreased aldosterone secretion
Resulting fall in blood pressure increases renin, angiotensin I, and angiotensin II levels
Streptococcus pneumoniae virulence factors (4)
- Polysaccharide capsule- impedes phagocytosis and complement binding
- IgA protease (inactivates secretory IgA)
- Adhesins (necessary for adhesion to epithelial cells)
- Pneumolysin (cytotoxin that causes pores in cell membrane and cell lysis)
C difficile 2 toxins
Disease via toxins
- Toxin A- enterotoxin- watery diarrhea
- Toxin B- cell necrosis/fibrin deposition
- both bind GI cells and are internalized
- DESTROY CYTOSKELETON OF GI CELLS—> pseudomembrane
GPCR and IP3 ligands
GnRH
TRH
ADH V1
Angiotensin II
Acute inflammation cells timeline
- Neutrophils dominate early (<2 days)
2. Monocytes/macrophages dominate late (>2 days). Live longer, replicate in tissues
Achondroplasia
Constitutive activation of FIBROBLAST GROWTH FACTOR RECEPTOR 3 (FGFR3)
Sporadic, but once mutation occurs, transmitted AUTOSOMAL DOMINANT
- 1 mutant copy of FGFR3 causes disorder
- 2 copies are lethal
Huntington disease
Atrophy of striatum in basal ganglia —> chorea, athetosis dt loss of GABAnergic neurons
Schizophreniform disorder
Psychotic symptoms (delusions, hallucinations, disorganized speech and behavior, negative symptoms) lasting more than 1 month and less than 6 mos
6 sulfa drugs
Furosemide Probenacid HCTZ Acetazolamide Sulfasalazine Sulfonylurea
Toxoplasmosis
- Immunocompetent host- mono like symptoms, negative heterophile ab test
- Reactivation in AIDS- brain abscesses seen as MULTIPLE RING ENHANCING LESIONS ON MRI.
- CD4<100
- HA, seizures - Congenital toxoplasmosis- chorioretinitis, hydrocephalus, INTRACRANIAL CALCIFICATIONS
Transmission- cysts in pork meat, oocysts in cat feces, crosses placenta
Isoproteronol
B1B2 sympathomimetic
Lowers BP (vasodilation)
Increase HR
Increase CO
- isoproteronol causes B2 mediated vasodilation, resulting in LOWERED MAP and INCREASED HR dt B1 reflex activity
Used in electrophysiologic evaluation of tachyarrythmias.
Can worsen ischemia
Negligible alpha effect
Burkitt lymphoma
Aggressive, high grade B cell lymphoma characterized by t(8;14)—> over activation of transcription factor C MYC (PROTO ONCOGENE)
Typically involves jaw, MC in equatorial Africa, usually associated with EBV
RB tumor suppressor
G1/S transition inhibitor
Inhibits E2F
Retinoblastoma
Osteosarcoma
ALA synthetase
Rate limiting step of heme synthesis
Stimulated by low levels of heme
B6 COFACTOR FOR ALA SYNTHETASE
von Gierke disease
Deficient glucose-6-phosphatase
- liver cannot break down glycogen into glucose
- glycogen accumulation causes hepatomegaly, renomegaly, growth retardation, profound fasting hypoglycemia
- also lactic acidosis, hypertriglyceridemia, hyperurucemia
Features: severe fasting hypoglycemia, lactic acidosis, hepatomegaly, hyperlipidemia, hyperuricemia, short stature, doll like face, protruding abdomen, emancipated extremities
Normal glucose structure
Fluoroquinolones MOA
Interfere with DNA replication by binding proteins such as DNA gyrase
Cerebral blood flow depends on
Systemic BP and ABG
PaCO2 most important regulator
A DROP IN PaCO2 DUE TO HYPERVENTILATION CAUSES VASOCONSTRICTION
- reduction in cerebral blood volume leads to decreased ICP
- lowering PaCO2 is a measure employed to REDUCE ICP in ventilated pts with cerebral edema
Tachypnea causes hypocapnia and cerebral vasoconstriction —> decrease cerebral blood volume and ICP
Cretinism
Fetal hypothyroidism dt
- antibody mediated maternal hypothyroidism
- Thyroid dysgenesis (MC in US)
- Iodine deficiency
- Dyshormogenic goiter (mutations in thyroid peroxidase)
FINDINGS:
- Pot bellied
- Pale
- Puffy face
- Protruding unbilicus
- Protuberant tongue
- Poor brain development
Thyroid hormone ha important interactions with growth hormone to promote bone growth—> if thyroid hormone affected, so is GH—> GH and thyroid hormone both share negative feedback involving somatotropin
Heinz bodies
Denatured Hb inclusions in RBCs in pts with G6PD deficiency in setting of hemolysis
Refsum disease
Defect in phytanic acid oxidase (peroxisomal enzyme reqd for initial step in FA metabolism)
Resulting accumulation of BCFA leads to their incorporation into phospholipids, which alters neuronal function and skin permeability
Retinitis pigmentosa is common complication- starts with night blindness and can progress to vision loss
Linkage disequilibrium
Tendency for certain alleles at 2 linked loci to occur together
High in alleles that are close
von Willebrand disease
vWF synthesized by endothelial cells and platelets and functions as carrier protein for factor 8
— vWF binds platelets to endothelium and other platelets
- absence of vWF leads to impaired platelet function and coagulation pathway abnormalities
MC HERITABLE BLEEDING DX, AD (both males and females)
Mild, easy bruising, skin bleeding, nose bleed, menorrhagia
NO platelet aggregation with RISTOCETIN COFACTOR ASSAY
- normally causes platelet aggregation IF vWF present, if no aggregation, vWF is defective
PROLONGED BLEEDING TIME- defect in platelet plug formation, low vWF—> defect in platelet to vWF adhesion
PROLONGED PTT- intrinsic pathway coag defect, low vWF—> high PTT because vWF carries/protects factor 8)
NORMAL PLATELET COUNT, PT
TREAT- DESMOPRESSIN (releases vWF stored in endothelium) or aminocaproic acid
Propionic acidemia
Presents in infancy- poor feeding, vomiting, hypotonia, high anion gap metabolic acidosis, hepatomegaly, seizures
Deficiency of propionyl coA carboxylase —> high propionyl coA and propionic acid, low methylmalonic acid
Organic acid accumulation:
1. Inhibit gluconeogenesis—> low fasting BG, HIGH ketoacidosis—> high anion gap metabolic acidosis
- Inhibits urea cycle- hyperammonemia
Tx: limit VOMIT (all metab into propionyl coA), propionyl coA carboxylase converts propionyl coA to succinylcoA to enter TCA cycle
Abx class to avoid with antacids
Fluoroquinolones (ciprofloxacin)
Annular pancreas
Dt abnormal migration of ventral pancreatic bud—> pancreatic tissue completely surrounds second part of duodenum, causing obstruction (pancreatitis, vomiting) or asymptomatic
Ventral bud is foregut derivative that appears by 5th week of gestation and rotates BEHIND duodenum during week 7
Ventral bud gives rise to uncinate process and main pancreatic duct
Body and tail derive from dorsal bud
Mature teratoma
MC type of ovarian germ cell neoplasm
Women 10-30
BENIGN
Show mature tissues derived from multiple germ layers (frequently include skin, hair, nails)
Reye syndrome histology
Fatty liver (microvesicular fatty changes) Mitochondrial abnormalities
Rare childhood hepatic encephalopathy associated with viral infection (VZV, influenza) that has been treated with aspirin
Aspirin metabolites decrease beta oxidation by reversible inhibition of mitochondrial enzymes
REM rebound
REM sleep is stage of sleep cycle where patients experience DREAMS
Can occur with DISCONTINUATION of medications or drugs that are known to suppress REM including
- alcohol
- barbiturates
- stimulants
- TCAs
- SSRIs
- lithium
- MAOIs
When REM sleep depressants stopped, compensatory in increase amount of REM sleep—> REM rebound
Frontal abscess
Direct spread of ethmoid or frontal sinus
Single abscess
Usually bacterial (viridans strep, s aureus)
Malic enzyme
Convert malate and NADP+ to pyruvate, CO2, and NADPH
Cytoplasmic enzyme in liver that produces NADPH for FA synthesis
This pathway works in G6PD deficiency pts
Polycythemia paraneoplastic syndrome in what 4 cancers
Ectopic EPO production —> stimulates erythropoiesis—> high Hct, reticulocytes, and total bilirubin
- HCC
- RCC
- Hemangioblastoma
- Pheochromacytoma
Urge incontinence
Detrusor hyperactivity
Sudden overwhelming urge to urinate
Ie MS- as disease progresses the bladder can become atonic and dilated leading to overflow incontinence
Isoniazid MOA
Inhibits mycolic acid synthesis
AE:
- neurotoxicity (give B6)
- hepatotoxic
Friedrichs ataxia
AR
GAA trinucleotide repeat dx—> reduces activity of FRATAXIN gene (
Frataxin is essential for mitochondrial function, involved in iron binding and storage —> absent frataxin causes free radical injury to mitochondria—> neuronal degradation
Dysarthria, ataxia, impaired position and vibration sense
Diphtheria
Diphtheria toxin- AB exotoxin that inhibits protein synthesis by ADP RIBOSYLATION
Toxin works locally causing respiratory cell necrosis with formation of fibrinous, coagulative exudates
Complications-
Suffocation
Myocarditis/ heart failure
Neurological toxicity
Congenital conjugated hyperbilirubinemia (black liver)
Dubin Johnson syndrome (inability of hepatocytes to secrete conjugated bilirubin into bile)
Stress hyperglycemia
Transient hyperglycemia without known DM
Risk factors: hemorrhage, major trauma, hypoxia, sepsis—> common in ICU
Severe metabolic stress associated with increased production of cortisol, catecholamines (NE, epi), glucagon, IL1, IL6, TNFa
—> act on liver to increase glycogenolysis and gluconeogensis, stimulating release of glucose from liver
IL1, IL6, TNFa associated with increased expression of GLUT1 (CNS, macrophages) and decreased GLUT4 (insulin induced glucose uptake in skeletal muscle and fat)—> facilitates increased glucose by brain and immune cells
West Nile Virus
Positive sense single strand RNA flavin iris transmitted by female mosquitos during summer months in southern US, Africa, Latin America
Fever, HA, rash
Neuroinvasive- MC in older patients with hx of malignancy, organ transplant, meningitis, confusion (encephalitis),ASYMMETRIC FLACCID PARALYSIS with concomitant Parkinsonism features (tremor, bradykinesia)
Sezary syndrome
T cell lymphoma affecting entire body
Widespread erythema (SKIN BRIGHT RED)
LAD
Malignant cells in blood (Sezary cells- cerebriform nuclei of T cells)
Basiliximab MOA and AE
mab that blocks IL2R
Factor Xa inhibitors directly inhibit
Conversion of prothrombin to thrombin
Anti GBM disease
Antibodies against type IV collagen in GBM
LM- glomerular crescents
IF- linear staining (IgG) along GBM
WT1 tumor suppressor
Urogenital differentiation
Wilms tumor (nephroblastoma)
Xeroderma pigmentosa
AR condition dt defects in NUCLEOTIDE EXCISION REPAIR
Children with severe sun burning after minimal UV exposure and signs of skin damage (freckling, actinic keratosis, hyperpigmentation, eye lesions)
High risk of skin cancer and blindness (dt cataracts or corneal ulcerations)
When DNA exposed to UV radiation—> thymidine dimers form—> absence of normal repair increases risk of DNA replication errors —> skin cancer
Ranolazine
Inhibits late Na current
Reduces calcium overload—> reduce wall tension and O2 demand
AE: Qt prolongation, Tdp
Multiple myeloma (CRAB)
hyperCalcemia
Renal insufficiency
Anemia
Bone lesions
Senna
Stimulant laxative
Enteric nerve stimulation—> colonic contraction
AE: MELANOSIS COLI
Rifampin MOA
Inhibits mycobacterial RNA transcription by targeting DNA dependent RNA polymerase
Methadone
Full mu opioid receptor AGONIST used for withdrawal and maintenance treatment of opioid use disorder
LONG HALF LIFE- suppresses cravings and withdrawal symptoms
Also blocks euphoric effects of other opioids by maintaining high tolerance levels
AE: QT PROLONGATION, respiratory depression
Shigella vs EHEC
Both produce shiga toxin
Both cause bloody diarrhea
Shigella- disease from bacterial invasion of mucosa, toxin less important in disease that invasion
EHEC- do not invade mucosa, disease from toxin (inflammation), toxin enters circulation and causes HUS
GAS special features
Pyrogenic- phayringitis, cellulitis, impetigo (honey crusted lesions), erysipelas
Toxigenic- scarlet fever (rash dt ERYTHROGENIC TOXIN), toxic shock like syndrome, necrotizing fasciitis
Immunologic- RF, poststreptococcal GN
PYRROLIDONYL ARYLAMIDASE (PYR+)
M protein inhibits phagocytosis
- abs to M protein enhance host against GAS but can give rise to RF
- ASO titter or anti DNase B abs indicate recent GAS infection
Most common site for ectopic pregnancy
Ampulla of Fallopian tube
Temporal arteritis
Risk of ipsilateral blindness dt occlusion of ophthalmic artery; polymyalgia rheumatica
Chronic myelogenous leukemia
Malignant dx of myeloid progenitor cells—> overproduction of granulocytes
- high numbers of neutrophils, basophils, eosinophils
- chronic phase:
- leukocytosis (100,000 wbc/mL), few blasts
HIGH BASOPHILS
Mild anemia, normal/increased platelets
Can progress to BLAST CRISIS
- acute leukemia (>20% blasts in periphery or marrow), usually myeloblasts
MUST R/O INFECTION TO DX CML—> LOW leukocyte alkaline phosphatase activity (will be high if infection, low in CML)
t(9;22) PHILADELPHIA CHROM IS GENETIC HALLMARK OF CML
- Bcr- abl fusion gene—> abnormal tyrosine kinase
Tx with IMATINIB
Bulbous cordis
Smooth parts of LV and RV
Glucose 6 phosphate dehydrogenase deficiency
X LINKED RECESSIVE
NADPH necessary to keep glutathione reduced, which detoxifies free radicals and peroxides
If no G6PD, cannot reduce glutathione via PPP—> less NADPH in RBCs leads to hemolytic anemia dt poor RBC defense against oxidizing agents (fava beans, sulfonamides, nitrofurantoin, primaquine/chloroquine, INH)
Infection can also produce hemolysis- inflammation produces free radicals that diffuse into RBCs and cause oxidative damage
BITE CELLS (results from splenic macrophages biting Heinz bodies out of RBCs) and HEINZ BODIES (denatured globin chains precipitate within RBCs dt oxidative stress)
Severe anemia results in
Widened pulse pressure
SBP-DBP
- SBP increases due to sympathetic mediated increase in cardiac contractility and stroke volume
- DBP decreases due to vasodilation caused by tissue hypoxia abs local accumulation of metabolites, CO2, H+
Anemia limits how much O2 blood can carry, forcing dependent tissues to compensate for reduced supply through locally mediated reflex vasodilation. SVR falls, PP widens
Bartholin gland cyst
Unilateral fluctuations mass of posterolateral vulva caused by obstruction of glands duct
Obstruction typically dt sequelae of previous infection
RAS proto oncogene
GTP binding protein
Cholangiocarcinoma
Pancreatic adenocarcinoma
Hypovolemic shock
Markedly decreased blood volume—> reduces CVP and CO—> leads to increased SVR (peripheral vasoconstriction)
Shock causes reduced organ and tissue perfusion, which leads to lactic acidosis (metabolic acidosis) and compensatory increase in ventilation (ie compensatory respiratory alkalosis)
Diabetic peripheral neuropathy
Numbness and parathesias in stocking and glove distribution
Results from nonenzymatic glycosylation of proteins, leading to hyalinization of endometrial arteries and ischemic nerve damage.
In addition, accumulation of sorbitol within neurons results in deranged metabolism and increased oxidative stress
Sturge Weber syndrome
Congenital vascular dx of capillaries - capillary malformation
- spontaneous mutation, NOT INHERITED
- somatic mutation in GNAQ
- Port wine stain in CN V1/V2 distribution
- Leptomeningeal angioma- occurs on SAME side as port wine stain, causes SEIZURES
- Increased ocular pressure (glaucoma)- in infancy/childhood
- vision impairment
Stroke volume affected by
Contractility
After load
Preload
HR
ADHD treatments and AEs
Psychostimulants- methylphenidate, amphetamines
Rapid onset of action
Common AES- decreased appetite, weight loss, insomnia
Less common- tics, high HR, HTN
Clomiphene MOA
Competitively binds estrogen receptors in hypothalamus and pituitary—> causing hypothalamus to perceive low estrogen—> increased GnRH release—> increased FSH AND LH release
Ovulation induction agent
Alport syndrome
Defective type IV collagen
EM- lamellated appearance of GBM
Alcohol withdrawal symptoms
Agitation Tremulousness Diaphoresis Confusion SNS overactivation- tachycardia, diaphoresis, HTN, seizures Hallucinations (visual and auditory)
Fibrates MOA
Gemfibrozil, fenofibrate, clofibrate
Lowers TRIGLYCERIDES and INCREASES HDL
Fibrates activate PPARalpha and INCREASES expression of lipoprotein lipases
AE- fibrates increase cholesterol in bile and therefore increase risk of gallstones.
Can cause rhabdomyolysis especially when combined with statins.
Glutamic acid is precursor of
GABA
Hypoxic pulmonary vasoconstriction
Limits perfusion to nonventilated alveoli, shunting blood toward better- ventilated ones, preserving ventilation- perfusion matching to maintain oxygenation.
Hypoxic pulmonary vasoconstriction can be impaired by inflammatory vasodilation (pneumonia, sepsis) and restoration of hypoxic pulmonary vasoconstriction optimizes oxygenation despite minimal improvement of ventilation of consolidated alveoli
TP53 tumor suppressor
Genomic stability
Most cancers
Li Fraumeni syndrome
Diffuse scleroderma autoab
Anti Scl 70 (anti DNA topoisomerase)
Anti-RNA polymerase III- high risk of renal crisis
Widespread disease- renal sclerosis, pulmonary fibrosis , heart block, pulmonary HTN
ASSOC WITH PRIMARY BILIARY CHOLANGITIS
Oligodendrocytes
Myelinates CNS axons
Most common glial cell in white matter
Destroyed in MS
Antiphospholipid syndrome blood treatment
WARFARIN
MOA- inhibits epoxied reductase which interferes with GAMMA CARBOXYLATION of vitamin K clotting factors 2,7,9,10, C and S
(Warfarin increases PT, effects EXTRINSIC pathway)
11 beta hydroxylase deficiency
CAH
Blocks aldosterone and cortisol synthesis, but pts present with HTN and hypokalemia dt accumulation of 11 deoxycorticosterone, a mineralcorticoid
Neonatal virilization occurs dt excess production of androgens
Spinothalamic tract
Ascending
Pain, temperature, crude touch
Decussates at spinal cord, where info enters spinal column
Myasthenia gravis
Autoimmune disease caused by abs targeting POST SYNAPTIC ACh receptors
Muscular weakness with diurnal variation
Worse at end of day
Associated with thymoma
TYPE II HSR
Dx: ERDROPHONIUM TEST (AChE inhibitor improves symptoms by increasing synaptic concentration of ACh at NMJ)
Tx: AChE inhibitors (pyridostigmine, neostigmine)
Neurokinin 1 receptor antagonists
Used in chemo induced N/V
- aprepitant, fosfoprepitant
NK1 inhibitors block the interaction between substance P and NK 1 in areas of brain stem that mediate vomiting (nucleus tract solitarius, area postrema)
Prevents central cause of vomiting/nausea
AE- neutropenia
Primary myelofibrosis
Excess collagen from fibroblasts —> marrow fibrosis
Stimulation by MEGAKARYOCYTE growth factors
- PDGF
- TGFb
Marrow failure—> EXTRAMEDULLARY HEMATOPOIESIS
- spleen, liver, LNs, CNS, lungs, bladder, skin
Older pts
Fatigue, night sweats, weight loss—> dt increased metabolism
MASSIVE SPLENOMEGALY
Smear- leukoerythroblastosis- immature erythrogenic abd granulocytic precursors in blood and TEAR DROP CELLS
SEVERE ANEMIA, HYPERURICEMIA (gout)
MC cause of unilateral fetal hydronephrosis disease
Inadequate canalization of ureteropelvic junction (connection between kidney and bladder)
Clostridium tetani MOA
Acts as protease that cleaves synaptobrevin, a SNARE protein → prevention of inhibitory neurotransmitters (i.e., GABA and glycine) release from Renshaw cells in the spinal cord → uninhibited activation of alpha motor neurons → muscle spasms, rigidity, and autonomic instability
Locked in syndrome
Quadriplegia and speechlessness (dt interruption of corticospinal and corticobulbar tracts) with preserved consciousness and vertical eye movements, eye opening, sensation
Caused by ischemic injury to VENTRAL PONS
Arteriosclerosis
Causes ISOLATED systolic HTN in elderly
SBP elevated and DBP remains the same
Age related calcification and deposition of connective tissue within walls of blood vessels reduces their compliance and limits the ability of the arterial tree to accommodate blood during systole and SBP rises to compensate.
Cephalosporins and disulfram reaction
Alcohol with cephalosporins
Warmth, flushing, sweating
Caused by inhibition of acetaldehyde dehydrogenase—> build up of acetaldehyde
H. influenzae type b vaccine contains
Conjugate vaccine
Contains polyribosyl ribitol phosphate (PRP) conjugated to toxoid protein
Vaccine gives significant protection against H influenzae meningitis and epiglottits
Major virulence factor is POLYSACCHARIDE CAPSULE
Fabry disease
Lysosomal storage dx
Deficient a galatosidase a
Neuropathy, skin lesions, lack of sweat, cardiac hypertrophy
Hyperaldosteronism (Conn syndrome)
HTN hypokalemia Metabolic alkalosis Decreased plasma renin - inappropriately high aldosterone suppresses renin as part of feedback loop
Medically treated with aldosterone antagonists
- spironolactone
- eplerenone (less side effects)
Shigella infectious dose
VERY LOW
As few as 10 Shigella organisms can cause disease
Prostaglandin that causes PAIN and FEVER
PGE2
Francisella tularensis
Facultative intracellular pathogen, slow growing, pale staining, aerobic, GN, requires cysteine for growth
Fever, LAD in animal carcass handlers (hunters)
Cell mediated immunity involving Th1 cells and macrophages is most important (TYPE IV HSR)
Medications causing erythema multiforme (5)
PCNs
Sulfonamides
Ciprofloxacin
Phenytoin, carbamazepine
Auer rod
Pathognomonic for AML
Accumulation of MPO
CAN CAUSE DIC
Most frequently injured nerve during axillary lymph node dissection
Intercostobrachial nerve
Results in SENSORY DYSFUNCTION (burning, numbness) to skin of axilla and medial upper arm
Lung adenocarcinoma
MC lung cancer
MC in women
Found in periphery
MC lung cancer in never smokers
Pericardial effusion s/s
Tachycardia
Low voltage QRS
Electrical alternans- beat to beat variation QRS axis
Chest tightness, dyspnea on exertion dt decreased diastolic ventricular filling which leads to decreased SV
Desmoplasia
Formation of benign collagenous stroma around neoplasms that provide connective tissue and support
Common in malignancy and is a reaction to tumor invasion of healthy tissue
Tumor of adrenal medulla in kids
Neuroblastoma (malignant)
Digoxin MOA
Positive inotropic agent
Increases parasympathetic tone
Slows AV conduction
Digoxin DIRECTLY inhibits Na K ATPase pump in myocardial cells—> decreased Na efflux (increased intracellular Na). The decreased transmembrane Na gradient reduces forward activity of Na Ca exchanger—> secondary decrease in Ca efflux from the cells.
Increased intracellular Ca concentration stimulates the binding of calcium to troponin C and subsequent actin myosin cross bridging—> improved myocyte contractility and LV systolic function
Cytosolic ONLY enzymes
Glycolysis
FA synthesis
Pentose phosphate pathway (TRANSKETOLASE)
Myotonic dystrophy
Trinucleotide repeat dx
CTG on chrom 19
Abnormal DMPK gene—> codes for myotonic dystrophy protein kinase
PROLONGED MUSCLE CONTRACTIONS- inability to release grip, locking of jaw
Long narrow face with hollow cheeks
Cataracts (at younger age)
Toupee- frontal balding
Gonad atrophy
Arrhythmias
Microangiopathic hemolytic anemia (HUS/DIC /TTP/SLE/HELLP/HTN emergency) or macroangiopathic hemolytic anemia (prosthetic heart valves, aortic stenosis) RBCs ON SMEAR
Schistocytes (HELMET CELLS)
Burr cells (also seen in pyruvate kinase deficiency)
Red blood cell fragments
Chancroid
Haemophilus ducreyi
PAINFUL GENITAL LESION
Multiple, deep ulcers
Base may have grey yellow exudate
Organisms clump in long parallel strands (school of fish)
Langerhans Cell Histiocytosis
Clonal proliferation of dendritic cells
Cells of myeloid origin
EXPRESS CD1a, S100, CD207
Contain Birbeck granules on EM (tennis racket shaped granules)
MC IN PEDS
OFTEN INVOLVES BONE AND SKIN
Lytic lesions, skin rash, recurrent otitis media with mass of mastoid bone
Stationary population
Stable population
declining birth rates
low mortality
long life expectancy
Developed countries
Hydroxyurea MOA
Inhibits ribonucleoside reductase
- enzyme generates deoxyribonueotise triphosphates for DNA synthesis/repair
- LACK of deoxyribonueoside triphosphates slows erythrocyte nuclear development—> less RBCs and bigger in size
- increases fetal Hb in SCD
CAN CAUSE PANCYTOPENIA in high doses
Friedrichs ataxia
Trinucleotide repeat dx- GAA
AR
Adolescent with progressive spinal cord and cerebral at degeneration
Associated with HYPERTROPHIC CARDIOMYOPATHY
Kyphoscoliosis, FOOT ABNORMALITIES
Secondary HTN
Renal artery stenosis
CKD (PCKD, diabetic nephropathy)
Hyperaldosteronism
Bleeding disorder with GpIb deficiency
Bernard Soulier syndrome (defect in platelet adhesion to von Willebrand factor
DIC caused by
Sepsis Ob complications Cancer Burns Trauma Major surgery Acute pancreatitis APL
Permissiveness (pharmacology)
A hormone has no direct effect on a physiological process but allows another hormone to exert its maximal effect on that process.
Example: cortisol and catecholamines
Galactokinase deficiency
Causes galactose buildup and the excess is converted to galactitol, an osmotic agent that causes cataracts
Excess galactose spills into urine—> reducing substance in urine
Infantile cataracts may be only manifestation.
Peripheral chemoreceptors for oxygen
Carotid and aortic bodies
Stimulated by hypoxemia
Primary Tb
Initial unchecked M tb replication within alveolar macrophages
After few weeks—> APCs in draining lymph system display mycobacterial antigens and release IL12, stimulates naive CD4 T cells to differentiate into Th1 cells that release IFN gamma—> activates more macrophages and causes them to:
- Form fully acidified phagolysosomes that can destroy intracellular mycobacterium
- DIFFERNTIATE INTO EPITHELIOD CELLS and multinucleated Langerhans giant cells that surround extracellular M Tb within granulomas
- these cells release digestive enzymes and generate ROS, which helps limit M Tb proliferation but also causes CASEOUS NECROSIS and cavitary lung lesions
Adenomyosis
Abnormal presence of endometrial glands and strong within uterine myometrium
Dysmenorrhea and uterine tenderness
UNIFORMLY ENLARGED UTERUS
regular, heavy menstrual bleeding
Common in multiparous women and prior uterine surgery (c section)
Aldesleukin
IL2 used for renal cell carcinoma and melanoma
Thought to work because activates NK cells
INH MOA
Inhibit mycolic acid synthesis
Can be neurotoxic
Raloxifene use and AE
Acts as estrogen antagonist on breast and endometrium receptors and agonist on bone receptors
Used for osteoporosis in pts who have contraindications to bisphosphonates or post menopausal F who benefit from breast cancer prophylaxis
Increased risk of thromboembolism
Galactokinase deficiency
Causes galactose buildup and the excess is converted to galactitol, an osmotic agent that causes cataracts
Excess galactose spills into urine—> reducing substance in urine
Infantile cataracts may be only manifestation.
Sarcomas spread
Hematogenously
Vitamin B5 (pantothenic acid)
Coenzyme A and fatty acid synthase
Deficiency- adrenal insufficiency, burning feet, alopecia
DIC and kidneys
Massive persistent activation of coagulation and fibrinolytic systems
Associated with DIFFUSE RENAL CORTICAL NECROSIS dt renal vessel thrombosis and ischemia (from diminished renal perfusion)
Reactive arthritis aka Reiter’s syndrome
Conjunctivitis
Urethritis (cervicitis in F)
Arthritis
Inflammatory arthropathy activates NEUTROPHILS
Synovial biopsy of joint will show inflammatory cells, neutrophils (similar profile to RA joint aspiration cell wise)
C difficile toxins
Toxin A- granulocytes attractant
Toxin B- cytopathic
DOES NOT INVADE BOWEL WALL
What drugs are relatively contraindicated in pts with bilateral renal artery stenosis?
ACEi and ARBs
Inhibit efferent arterioles constriction, which can lead to decreased GFR and AKI
Pts with bilateral RAS are especially susceptible to this effect because the kidneys rely on efferent arteriole constriction to maintain GFR
Microglia
CNS macrophages
Proliferate in response to injury
HIV can persist in brain via microglia
- chronic HIV encephalitis: nodules of activated microglia
Coccidiomycosis
Southwest US, California
VALLEY FEVER:
- Fever, malaise, cough
- ERYTHEMA NODOSUM (inflammation of subq fat)
- Joint pain
Dx: sputum culture—> SPHERULES FILLED WITH TINY ENDOSPORES
Can cause MENINGITIS
Maintenance dose
Maintenance dose=clearance * (plasma concentration at steady state)/F
Ataxia telangiectasia
Defective nonhomologous end joining
Mutation chromosome 11 in ATM gene
DNA hypertensive to ionizing radiation
CNS, skin, immune system affected
Hemolytic uremic syndrome
Caused by shiga toxin producing bacteria- toxin injure endothelium of preglomerular arterioles abs glomerular capillaries—> platelet activation and activation, form thrombi
- E. coli O157H7
- shigella
Clinically: antecedent diarrheal illness (often bloody)
Hemolytic anemia with schistocytes
THROMBOCYTOPENIA- platelet consumption with no bleeding/petechiae
Acute kidney injury
Barbiturate vs benzodiazepine MOA
Barbiturates (phenobarbital) potentiates GABA by INCREASING DURATION OF GABA LIGAND GATED CL CHANNEL OPEN
- safety issues, used for induction of anesthesia
Benzodiazepines (lorazepam, diazepam)potentials GABA by INCREASING FREQUENCY OF GABA CHANNEL OPENING
Polycythemia vera complications
- Spent phase (progression to myelofibrosis)
- Leukemia (usually AML)
- GOUT (high purine metabolism—> high uric acid. Also seen in CML)
Carbamazepine risk in pregnancy
NTD
Carbamazepine is folate inhibitor
Stevens Johnson Syndrome
Type IV HSR- usually triggered by drugs
NECROSIS OF EPIDERMIS, usually triggered by drugs, may involve mucus membranes
- prone to infections
- lose water
- lose protection of epidermis
+ Nikolsky sign
Prodrome - 1-3 days fever, malaise
Lesions start on FACE/ CHEST
spreads symmetrically, red tender skin, progresses to bullae—> SLOUGHING OF SKIN
Toxic epidermal necrolysis- >30% of skin
Infections in CGD
S aureus
E. coli
Aspergillus
Hairy cell leukemia
Rare MATURE B cell malignancy
C19, CD20, CD22,
CD103–> (sensitive marker)
MASSIVE SPLENOMEGALY- red pulp engorged, atrophy/ obliteration of white pulp
DRY TAP- hairy cells induce marrow fibrosis
TARTRATE RESISTANT ACID PHOSPHATASE (TRAP) +
- cellular enzyme, hairy cells have strong positivity for TRAP stain
- TRAP + assoc with BRAF mutation
Average age of dx 52yo, pts usually present with ABDOMINAL PAIN—> massive spleen, bone marrow suppression
Tx w CLADRIBINE- adenosine analog, highly toxic to HCL cells
TCA toxicity (3 Cs)
Coma
Convulsions
Cardiac arrhythmias
Side effects with alpha1 blockade (orthostatic hypotension) and muscarinic blockade (tachycardia, constipation, urinary retention, dry mouth)
Citrates effects on PFK1 and acetyl coA carboxylase
Citrate allosterically inhibits PFK1
Citrate is a positive allosteric regulator of acetyl coA carboxylase- rate limiting and regulated step of FA synthesis
Primitive pulmonary vein
Smooth part of LA
Bacterial meningitis in infants and kids
GBS
E coli
L monocytogenes (infants)
S pneumoniae/ N meningiditis (kids/teens)
Anti emetic choice caused by GI irritation (infections, chemotherapy, distention)
GI Irritation cause increased mucosal serotonin and activation of 5HT3 receptors on vagal and spinal afferents
USE 5HT3 receptor ANTAGONISTS
- ondansetron
Primary carnitine deficiency
Caused by defect in protein responsible for carnitine transport across the mitochondrial membrane
Without carnitine, fatty acids cannot be transported into mitochondria as acyl carnitine
Mitochondria cannot beta oxidize the fatty acids into acetyl coA for TCA—> cardiac and skeletal myocytes cannot generate ATP from FAs—> weakness, cardiomyopathy and liver cannot synthesize ketone bodies (hypoketotic hypoglycemia- cannot make acetoacetate or beta hydroxybutyrate)
Clearance eqn
Clearance = volume of plasma cleared of drug per unit time
CL=(0.7*Vd)/t1/2
Rifampin MOA
Inhibition of bacterial DNA dependent RNA polymerase
Mantle cell lymphoma
B cell lymphoma
Express CD19, CD20, CD5
Poor prognosis, cancer of older pts (70yo)
t(11;14) —> OVEREXPRESSION OF CYCLIN D1–> promotes cell cycle transition from G1 to S
Primary carnitine deficiency
Caused by defect in protein responsible for carnitine transport across the mitochondrial membrane
Without carnitine, fatty acids cannot be transported into mitochondria as acyl carnitine
Mitochondria cannot beta oxidize the fatty acids into acetyl coA for TCA—> cardiac and skeletal myocytes cannot generate ATP from FAs—> weakness, cardiomyopathy and liver cannot synthesize ketone bodies (hypoketotic hypoglycemia- cannot make acetoacetate or beta hydroxybutyrate)
HCV and proofreading
Lacks 3’ to 5’ exonuclease activity —> no proofreading ability—> HCV envelope antigenic variation
Panic disorder
Recurrent UNEXPECTED panic attacks
Uterine curettage in ectopic pregnancy
Decidualized endometrium- dilated, coiled endometrial glands and vascularized edematous storma
These changes occur in LUTEAL PHASE under the influence of progesterone, as the endometrium prepares for implantation
Watery diarrhea
Non inflammatory (exotoxin)
No WBCs, no RBCs
V cholera and ETEC—> purely toxin mediated watery diarrhea
Toxins secreted by these organisms modify electrolyte handling by enterocytes but do not cause cell death. No RBCs or WBCs on stool microscopy
Chloramphenicol
Inhibits ribosomal peptidyl transferase at 50S subunit
Interferes with bacterial protein synthesis
Causes grey baby syndrome- infants cannot break down high doses of drug which results in cardiovascular collapse and ashen skin color
- infants lack glucuronyl transferase
- infants have inadequate renal excretion
High risk of aplastic anemia
Cardiopulmonary changes immediately after birth (3)
- Decreased pulmonary vascular resistance (dt oxygenation and ventilation of lungs- pulmonary vasodilation)
- Increased SVR (dt removal of low resistance placenta)
- LV responsible for entire CO (RV no longer contributes to systemic flow)
Reactive (atypical) lymphocyte
Scalloped edges with abundant cytoplasm
Activated, pathogen specific cytotoxic T cells and NK cells that form in response to INTRACELLULAR INFECTIONS
- EBV
- HIV
- CMV
Contain PERFORIN (holes in infected cell membrane) and GRANZYMES (enter cytoplasm and trigger cell death)
PropionylcoA
Ultimate product of beta oxidation of OCFA
Metabolized into succinylcoA in vitamin B12 dependent process
Elevated propionyl coA in cells can be used by citrate synthase as a substrate to generate methyl citrate (marker of B12 deficiency, or defect in propionyl coA carboxylase or methylmalonyl coA mutase)
- B12 def neuropathy can be caused in part by incorporation of methylmalonyl coA into FA synthesis —> FAs incorporated into phospholipids in nervous system—> altered myelin sheath around neurons diminishing neuron function
Amphotericin B AE
Used for serious systemic mycoses, forms membrane pores that allow electrolytes to leak out, and binds ergosterol
Nephrotoxic- decrease in GFR and toxic to tubular epithelium, RTA type I
Hypokalemia and hypomag because of altered renal tubule permeability—> arrhythmias- SUPPLEMENT K AND MG
Fever and chills—> shake and bake, phlebitis, nephrogenic DI
FENa
<1% PRE RENAL
> 1% INTRINSIC
> 4% POST RENAL
FENa is % of Na excreted in urine
Temporal lobe abscess
Single brain abscess usually caused by direct spread of a contiguous infection
Temporal lobe abscess usually a result of otitis media that spread to mastoid air cells
Usually bacterial (viridans strep, s aureus)
Eosin Methylene Blue agar
E. coli
Lactose fermenters (E coli) appears as colonies with GREEN METALLIC SHEEN or blue-black to brown color
Bacteria that do not ferment lactose appear as colorless or transparent
P450 inducers
Chronic EtOH Carbamazepine Phenobarbital Phenytoin Rifampin Griseofulvin St. John’s wort Modafinil Cyclophosphamide
Richter transformation
CLL/SLL that transforms to aggressive DIFFUSE LARGE B CELL LYMPHOMA
- classic presentation:
Pt w known CLL has rapid growth of single LN
On bx- diffuse large B cell lymphoma
Secretory phase of menstrual cycle
Between ovulation and menses (days 15-28)
Progesterone released by corpus luteum causes uterine glands to coil and secrete glycogen rich mucus in preparation for embryo implantation
Endometrial storms is edematous and completely traversed by spiral arteries
Effect modification
Effect modification is present when the effect of the main exposure on the outcome is modified by the presence of another variable
HBV 3 key features
- Partially dsDNA virus
- genome enters hepatocyte—> nucleus—> DNA becomes fully add—> mRNA synthesized—> cytoplasm - Reverse transcriptase synthesized
- viral mRNA—> viral DNA, packaged in capsid - Envelope from ENDOPLASMIC RETICULUM
Rett syndrome
Sporadic X linked, mostly girls
Normal development until 6-18 months then REGRESSION OF SPEECH, loss of purposeful movements, repeated hand movements (clapping, hand wringing) and gait abnormalities
MECP2 gene mutated—> ARRESTED BRAIN DEVELOPMENT (impaired dendritic maturation, reduced neuro melanin in substantia nigra)
Hydroxyurea
Inhibits ribonucleotide reductive
Blocks formation of deoxynucleotides (RNA intact)
Used in polycythemia Vera, essential thrombocytosis, SCD
C botulism symptoms (4 Ds)
Diplopia
Dysphasia
Dysphona
Dyspnea
Sirolimus MOA and AE
mTOR inhibitor
Prevents response to IL2
Kidney transplant rejection prophylaxis
AE- pancytopenia
Carcinomas spread via
Lymphatic
Hepatoduodenal ligament
Liver to duodenum
Contains PORTAL TRIAD:
- hepatic artery proper
- portal vein
- common bile duct
Ventral mesentery
PRINGLE MANEUVER—> ligament compressed in omental foramen to control bleeding from hepatic inflow source
Borders omental foramen which connects greater and lesser sacs
Atypical lymphocytes seen in EBV
CD8+ T cells
Reactive against EBV infected B cells
EBV infection- + heterophile ab test
Methamphetamine MOA
Gain entrance to dopamine, NE, serotonin nerve terminals and cause RELEASE OF THESE NEUROTRANSMITTERS by reversing the direction of the transporters that usually mediate neurotransmitter uptake from synaptic cleft
Dopamine plays important role in reward system of brain and in reinforcing effects of stimulants
Nucleus accumbens impt in dopaminergic reward pathway
DiGeorge syndrome
Caused by abnormal 3 and 4 pharyngeal pouch development and abnormal neural crest cell migration dt chromosome 22 abnormalities
- Craniofacial malformations (cleft palate, low set ears, micrognathia)
- Partial or total agenesis of derivatives of pharyngeal pouches 3 and 4 (no parathyroid hormone or thymus tissue, resulting in hypocalcemia and impaired immune system dt T cell deficiency)
- Cardiac anomalies (persistent truncus arteriosus bc NCC fail to properly form aorticopulmonary septum)
ARDS
Aka diffuse alveolar damage
Acute respiratory failure resulting from diffuse injury to the alveolar/capillary barrier. B/l infiltrates abs opacity seen on CXR
Caused by shock, severe trauma, sepsis, ACUTE PANCREATITS, massive transfusion, gastric aspiration
NEUTROPHIL DEPENDENT INJURY to alveolar/capillary endothelium
- neutrophils accumulate in lung microvasculature. Release chemokines, oxygen radicals, prostaglandins, proteases
- vascular injury and capillary permeability cause fluid to leak—> protein rich pulmonary edema and hyaline membrane formation
- accumulation of hyaline membranes, increased inflammation cause intrapulmonary pulmonary shunting, hypoxemia, and decreased CO2 excretion
PaO2/FiO2 <200 diagnostic for ARDS
Primary goal of medical therapy for acute aortic dissection
Reduce aortic wall shear stress to limit extension of dissection
Accomplished by anti impulse therapy to decrease rate of change in aortic BP per time
ESMOLOL
- decreased LV contractility (reduce SV) to decrease rise in BP with each contraction
- decreased HR- subjecting aorta to fewer VL contractions per minute (less BP change)
Pinealoma
Pineal gland tumors compress VERTICAL gaze center in tectum of brain
Can lead to Parinaud syndrome
- eye movement and pupil dysfunction—> vertical gaze palsy and light near dissociation
Metolazone
Thiazides diuretic
Potentiates the diuretic effect of loop diuretics, can be helpful in refractory volume overload (decompensated HF)
Na excretion caused by loop diuretics is limited by reabsorption of Na in DCT- the Na Cl cotransporter in DCT counteracts loops by reabsorbing much of the Na that was not reabsorbed in the TAL
- inhibition of Na Cl cotransporter with METOLAZONE prevents reabsorption of increased Na delivered to DCT, significantly increasing total Na excretion
COPD and HYPOXIC DRIVE
COPD pts have decreased sensitivity to PaCO2 (dt chronic CO2 retention) AND may have profound hypoxemia (PaO2 <60), therefore PaO2 levels become a significant contributor to respiratory drive
Peripheral chemoreceptors in carotid and aortic bodies are primary sites for sensing PaO2 and are stimulated by hypoxemia
Supplemental oxygen rapidly increases PaO2 and reduces peripheral chemoreceptor stimulation and decreases the respiratory rate
Mismatch repair
Identifies INCORRECTLY PLACED bases/nucleotides
- occurs when proofreading misses error- no damage to base
- repairs DNA slippage and keeps microsatellites stable
-OCCURS S/G2 phase
- microsatellite INSTABILITY occurs when MMR deficient —> occurs in colon cancer (Lynch syndrome- germline mutation of DNA MMR enzymes
- mutations in MLH1 and MLH2)
IL8
Attracts neutrophils
Macrophage secreted
Side effect of adding carbidopa to levodopa
Anxiety and agitation
- more dopamine available to the brain
PCN and type III HSR
Serum sickness- days to weeks after exposure, complement activation
IgG
Circulating abs-ag complexes deposit in tissues and cause diffuse symptoms- fever, urticaria, arthritis
Phenytoin and carbamazepine MOA
Blocks Na channels
Phenytoin decrease Na current in cortical neurons by reducing ability of Na channel to recover from inactivation increases refractory period, inhibits neuronal high frequency firing
Protein A virulence factor
Staph aureus
Part of peptidoglycan cell wall, inhibits phagocytosis by BINDING Fc PORTION OF IgG antibodies—> prevents opsonization and phagocytosis by macrophages
Prevents complement activation
Hereditary hemorrhagic telangiectasia aka Osler Weber Rendu syndrome
AD
Recurrent epistaxis
Melena
Multiple cutaneous and mucosal vascular lesions
Propensity to develop AVMs in brain, lungs, liver. Cerebral AVMs produce seizures
Pts may develop high output heart failure dt AVMs
May develop secondary polycythemia dt EPO secretion from chronic hypoxia dt right to left shunting via pulmonary AVMs
Pts may devo iron deficiency anemia dt bleeding episodes
Aortic dissection
HTN
Phase I reactions
P450
Reduction
Oxidation
Hydrolysis
(Polar) Water soluble metabolite
Geriatrics lose phase I first
Acute lymphoblastic leukemia
Usually children
Tdt+
Usually pre B cell malignancy (CD10+, CD19+, CD+20)
Treated with chemo-> may need intrathecal chemo, testical chemo dt “sanctuary sites”- testes and CNS have poor penetration of chemo, relapse may occur in these locations
Philadelphia chromosome (t9;22)
- ALL in adults, not children
- POOR PROGNOSIS
t(12;21)
- fusion of TEL-AML1–> impairs differentiation of blasts
- GOOD PROGNOSIS, MC rearrangement in children
ASSOC WITH DOWN SYNDROME
Smear shows HIGH LYMPHOBLASTS
mecA gene
Mobile genetic element that encodes for penicillin binding proteins (PBP2a) that has LOW affinity for beta lactam abx
Must treat MRSA with non beta lactam ie TMP SMX (inhibits 2 steps in folate synthesis), clindamycin (binds 50S subunit), doxycycline (binds 30S subunit), vancomycin (inhibits integration of peptidoglycan subunits)
Found in MRSA which can grow in oxacillin because of mecA gene
c KIT mutation
Proto oncogene
Tyrosine kinase receptor—> stimulates growth
CD117+
Gain of function mutation in 95% of GI stromal tumors (GISTs)
Treat with IMATINIB
Uremia and bleeding risk
Uremia causes platelet aggregation dysfunction
- Prolonged bleeding time with normal platelets, normal PT, normal aPTT
Edwards syndrome
Trisomy 18
Dt meiotic non disjunction
Micrognathia, low set ears, prominent occiput, rocker bottom feet, clenched hands, overlapping fingers, horseshoe kidney, VSD/PDA
Amiodarone risks
Anti arrhythmic class III - K channel blocker in phase 3
AE: pulmonary fibrosis, hepatotoxic, hypothyroidism OR hyperthyroidism
Acts as HAPTEN- corneal deposits, blue/grey skin
Neurological effects
Constipation
Bradycardia, heart block, HF
CHECK PFTs, LFTs, TFTs
Has class I, II, III, IV effects - lipophilic
Occlusion of anterior cerebral artery
Contra lateral motor and sensory deficits of LE, behavioral changes, urinary incontinence
Anterior cerebral arteries supply medial portions of the 2 hemispheres (frontal and parietal lobes)
Tregs
CD3, CD4, CD25, FOXP3 identification markers
Produce anti inflamm- IL10 aND TGFb
M2 moa
Heart: negative chronotrope and ↓ contractility of atria
Functions via Gi
NOT FOUND IN BLOOD VESSELS
SIADH and euvolemic hyponatremia mechanism
In SIADH, increased ADH causes excessive water absorption by the kidneys leading to transient sun clinical hypervolemia
Mild increase in extracellular fluid volume suppresses the renin aldosterone axis and stimulates the production of natriuretic peptides—> excretion of sodium in urine (natriuresis)
As a result, pts with SIADH have clinically normal extracellular fluid volume and low plasma osmolarity (euvolemic hyponatremia)
Features of volume overload (edema, crackles, JVP) not seen.
Neutrophil transmigration
Cross endothelium into tissues
Neutrophils bind PECAM 1 between endothelial cells
Organophosphate toxicity
Cholinesterase inhibitors, used as pesticides
Excess muscarinic stimulation (salivation, miosis, bronchospasm, bradycardia)
Tx: ATROPINE (competitively inhibit postganglionic muscarinic receptors)
However, pts at risk for paralysis dt NICOTINIC over activation—> need to treat with PRALIDOXIME (cholinesterase reactivating agent)
3 reactions in both cytoplasm and mitochondria (HUGs take both)
Heme synthesis
Urea cycle
Gluconeogenesis
Clomipramine
TCA used for OCD when SSRIs have failed
TCAs inhibit 5HT and NE reuptake
Pyruvate carboxylase deficiency
Pyruvate carboxylase is mitochondrial enzyme that catalyzes formation of OAA from pyruvate
Deficiency if pyruvate carboxylase leads to accumulation of gluconeogenic precursors alanine, pyruvate, and lactate because cannot perform gluconeogenesis
AUTOSOMAL RECESSIVE
Hypoglycemia, elevated alanine, pyruvate, lactate, and ketoacids
Programmed death receptor 1 (PD1) function and anti cancer target mechanism
PD1 is found on cytotoxic T cells and when bound by its ligand, down regulates cytotoxic T cell response. Neoplasticism cells exploit this and over express PD1 ligand—> suppresses T cell ability to induce apoptosis in cancer cells
Pembrolizumab (PD1 receptor inhibitor) restores T cell response, which promotes tumor cell apoptosis and allows cytotoxic T cells to invade tumor cells
Hypospadias
Congenital displacement of urethral opening dt malformation of urethral groove and canal
Can lead to infertility
Vascular dementia
Ischemia and/or infarcts dt
- large vessel atherosclerosis
- small vessel disease (arteriosclerosis)
- cerebral amyloid angiopathy
S/s
- early, prominent executive dysfunction
- multi infarcts- often stepwise decline
- strategic infarct- localizing cortical deficits
- subcortical vascular encephalopathy: subcritical deficits (urinary incontinence, gait problems)
Imaging- SCATTERED LESIONS IN WHITE MATTER AND SUBCORTICAL GREY MATTER, ESPECIALLY THALAMUS
- cortical infarcts
- subcortical lacunar infarcts
- white matter hyperintensities
What do T cells recognize
PEPTIDES ONLY
Reed Sternberg cells
Malignant cells that cause HODGKIN LYMPHOMA
Large cells with MULTILOBED NUCLEUS, “OWL EYED”, usually B cells
CD15 and CD30 POSITIVE
- NOT positive for typical B cell markers
Lepromin skin test
M leprae antigens injected into skin distinguish tuberculoid vs lepromatous leprosy
Tuberculoid pts will develop hard indurated nodule at inj site—> strong Th1 response
Lepromatous pts are nonreactive to test dt no Th1 response
Pentode phosphate pathway
Generates NADPH and RIBOSE 5 PHOSPHATE (nucleotide precursor)
Consists of 2 types of rxns oxidative (irreversible) and nonoxidative (reversible)
- both can function independently depending on cell requirements
NONOXIDATIVE rxns governed by cells need for ribose 5 phosphate
- when ribose 5 phosphate produced in excess—> TRANSKETOLASE can produce glycolytic intermediates for ATP generation
- when ribose 5 phosphate demand EXCEEDS oxidative pathway—> nonoxidative pathway reverses and TRANSKETOLASE can make ribose 5 phosphate from glycolytic intermediates
PPP occurs in:
Lactating mammary gland, liver, adrenal cortex, RBCs
DMD inheritance
X LINKED RECESSIVE
Carrier mother’s pass disease to sons
NK cells important for (2)
- Kill human cells infected by viruses and human cells with REDUCED MHCI
- Produce IFN gamma to activate macrophages
MAOI mechanism
Inhibit oxidative deamination—> increases presynaptic ability of serotonin, NE, epi, and DA
Th2 cytokines
IL4- activates Th2, suppresses Th1, PROMOTES IgE PRODUCTION (parasites)
IL5- activates eosinophils (helminths), PROMOTES IgA PRODUCTION (GI bacteria)
IL10- inhibits Th1, ANTI INFLAMMATORYl
Th2 involved in humoral immunity- drive Ab mediated response
Celiac disease
Hypersensitivity to gluten
Gliadin triggers immune mediated reaction causing VILLOUS ATROPHY, CRYPT HYPERPLASIA, INTREPITHELIAL LYMPHOCYTE INFILTRATION —> impaired nutrient absorption in duodenum and proximal jejunum
Classically presents at age 6-24 months w abd pain, diarrhea, v, weight loss
Elevated IgA anti endomysial and anti TTG
Dx confirmed with bx. Gluten free diet to tx
Immunohistochemistry stain for complete hydatiform mole
p57 negative
Complete mole- 46XX or XY- all paternal DNA
Trophoblastic proliferation and edematous chorionic villi
Bunch of grapes appearance, “snowstorm pattern” on us
NO FETAL EMBRYONIC TISSUE
Death in CML
Blast crisis
Cromolyn
Mast cell stabilizing agents that inhibit mast cell degranulation independent of the triggering stimulus
Less effective than inhaled glucocorticoids
2nd line therapy for asthma
Buprenorphine
Partial agonist (used alone or with naloxone- opioid antagonist) for opioid use disorder
Less likely to cause respiratory depression.
Rheumatic fever
Consequence of GAS pharyngeal infection
Infects mitral valve> aortic> tricuspid (high pressure valves affected most)
Aschoff bodies and Anitschkow cells
High anti streptolysin O (ASO) and high anti DNase B
TYPE II HSR- abs to M protein crisis rwact with self antigens in myosin (molecular mimicry)
Treat with PCN
Pseudoappendicitis
Presents as appendicitis:
RLQ pain, fever, vomiting, leukocytosis
Caused by mesenteric lymphadenitis from complication of Yersinia infection (Y enterolitica contaminated from raw pork)
Carbachol and pilocarpine
Cholinergic agonists
Used to lower intra ocular pressure in glaucoma
- cholinergic associated miosis causes iris to move farther from cornea. This widens the anterior chamber angle and allows for better outflow of aqueous humor
Carbapenems
Bind transpeptidases and prevent peptidoglycan cross linking
Beta lactamases, but NOT PCNs
Resistant to cleavage by most beta lactamases
Used for ESBLs, B fragilis, pseudomonas and enterobacter
Imipenem-give with cilastatin (inhibits dehydropeptidase I) to decrease nephrotoxicity
Staphylococcus aureus PNA
Post influenza bacterial PNA with CAVITARY LESIONS and SALMON COLORED SPUTUM
Can for lung abscesses
S aureus is very destructive to lung tissue p
Nucleolus function
Site of ribosomal subunit maturation and assembly
RNA POL1 functions exclusively in nucleolus to transcribe pre rRNA gene
Drugs that cause SIADH (4)
Antidepressants- SSRI, MAOis, tricyclics
Antipsychotics
Anticonvulsants- carbamazepine
Antineoplastics- cyclophosphamide
Acetazolamide MOA
Block carbonic anhydrase in PCT, thereby inhibiting Na Cl and bicarbonate reabsorption
The resulting osmotic diuresis increases Na Cl delivery to macula densa (located in TAL)
Glomerular afferent arteriolar resistance will increase as a result of tubuloglomerular feedback
Poststreptococcal glomerulonephritis
Follows either GAS pharyngitis or skin infection
Dark urine, periorbital edema, HTN, oliguria
SUBEPITHELIAL HUMPS ON EM
GRANULAR PATTER OF IGG IGM AND C3 ON IF
Tamoxifen MOA and AE
Selective Estrogen Receptor Modulator (SERM)
Antagonistic effects on breast tissue (used for ER + breast ca)
Agonist effects on bone and uterine tissue
Post menopausal women on tamoxifen have 2-3x risk of endometrial cancer
Neimann Pick
Sphingomyelinase deficiency —> sphingomyelin accumulation in lysosomes of CNS and reticuloendothelial system
Cherry red spot on macula
Hepatomegaly
Microcephaly, severe MR
ZEBRA BODIES IN INCLUSIONS
FOAMY MACROPHAGES
Serotonin syndrome triad
Autonomic instability- hyperthermia, HTN, tachycardia
AMS- agitation, confusion
Neuromuscular hyperactivity- tremor, hyperreflexia, myoclonus
Causes:
1 serotonergic meds- SSRI/SNRI, TCA, tramadol
2 drug interactions: serotonergic med + MAOI or LINEZOLID
3 overdose or abuse
Eosinophilic granulomatosis with polyangiitis
Asthma, chronic sinusitis, peripheral neuropathy, subQ nodules
Peripheral eosinophilia and glomerulonephritis
Pauci immune glomerulonephritis
p ANCA positive
Protein synthesis inhibitors (4)
Exotoxins that’s inhibit host cell protein synthesis:
C. Diptheria- diphtheria toxin
P aeroginosa- exotoxins A
- inhibits E2F
Shigella- shiga toxin
EHEC- shiga like toxin
- INACTIVATES 60s ribosome
Propionyl coA importance
Way for VALINE, ODD CHAIN FAS, METHIONINE, ISOLEUCINE, THREONINE to enter TCA cycle
Malonyl coA importance
Produced by acetyl coA to malonyl coA in rate limiting step of Fa synthesis by acetylcoA carboxylase
Malonyl coA inhibits carnitine shuttle—> prevents breakdown of FAs
Thyroid cancer
Papillary carcinoma (childhood radiation)
Class IA anti arrhythmics
Quinidine
Procainamide
Disopyramide
Na channel blocker, intermediate use dependence
Infraspinatus
External rotation of arm at shoulder
Innervated by suprascapular nerve
Normally, metabolic acidosis is partially compensated for by respiratory alkalosis
When steady state PaCO2 persists above range given by winters formula, the patient has a superimposed respiratory acidosis (respiratory failure)
Winters formula:
PaCO2 = (1.5*bicarB) + 8 +/- 2
Sirolimus
Binds FKBP and inhibits mTOR—> interrupts IL2 signaling and prevents G1 to S phase progression and lymphocyte proliferation
Nucleolus function
Site of ribosomal subunit maturation and assembly
RNA POL1 functions exclusively in nucleolus to transcribe pre rRNA gene
Tacrolimus MOA and AE
Calcineurin inhibitor, binds FK506 and prevents IL2 transcription
No gingival hyperplasia, hirsutism
APC/ beta catenin tumor suppressor
Wnt signaling
Colon, gastric, pancreatic cancer
FAP
Collagen lysine and proline hydroxylation occurs where
RER
Vitamin c req as cofactor
Defective hydroxylation finishes the amount of collagen secreted by fibroblasts and impairs triple helix stability and covalent cross linking
Primary amyloidosis
Multiple myeloma
Waldenstrom macroglobulinemia
Ig light chains —> increased production —> amyloid light chain (AL) deposition
Kidney, spleen, liver, heart, peripheral nerves, tongue, skin
Lambert Eaton syndrome
Antibodies directed towards PRE SYNAPTIC voltage gated calcium channels
Usually in association with SCLC
Malonyl coA importance
Produced by acetyl coA to malonyl coA in rate limiting step of Fa synthesis by acetylcoA carboxylase
Malonyl coA inhibits carnitine shuttle—> prevents breakdown of FAs
Coronary steal potentiating drugs
Chemical stress testing
- use vasodilators to induce coronary steal to test for
Antipseudomonal PCNs
Greater porin penetration
Ticarcillin, pipercillin
- usually given with beta lactamase inhibitor
DO NOT COVER MRSA
Hospitalized patients with sepsis/PNA dt GNs
S4
Stiff/hypertrophic ventricle
Aortic stenosis, restrictive cardiomyopathy
Chronic HTN causes LVH which may promote S4
Sound results from atrial contraction which forces blood into LV that’s reached its limit of compliance
“Presystolic” “late diastolic”
Best heard at cardiac apex at PMI in left lateral decubitus position
Microglia
CNS macrophages
Proliferate in response to injury
HIV can persist in brain via microglia
- chronic HIV encephalitis: nodules of activated microglia
Neural crest cell immunochemical stain
S100
What structures are drained by right lymphatic duct?
Right upper limb
Right side of head
Drains into right subclavian
Ascaris lumbricoides
Nematode that’s acquired by ingestion of ova in fecally contaminated soil
Cylindrical, very long
Ingest eggs—> larvae hatch and migrate to lungs (cough, dyspnea)—> mature in GIT (abdominal pain, diarrhea)
Tx with albendazole or mebendazole
Collagen lysine and proline hydroxylation occurs where
RER
Vitamin c req as cofactor
Defective hydroxylation finishes the amount of collagen secreted by fibroblasts and impairs triple helix stability and covalent cross linking
