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
Supraspinatus
Abduction of arm 0 to 15
Suprascapular nerve
MC injury to rotator cuff
Liver metabolism of acetaminophen
Mostly conveyed to nontoxic metabolites by sulfation and glucuronidation, small amount metab by cytochrome P450 into TOXIC metabolite NAPQI
Tylenol overdose depletes glutathione —> high NAPQI and liver toxicity
ACUTE EtOH ingestion can reduce Tylenol hepatotoxicity—> acute EtOH competitively inhibits cytochrome P450 and decrease metab of Tylenol to NAPQI
Chronic EtOH increases NAPQI by INDUCTION of P450 and risk of liver toxicity if Tylenol overdose mixed with chronic alcoholism
Dialysis related amyloidosis
ESRD
Dialysis >5 years
Beta2 microglobulin—> decreased clearance —> amyloid beta2-m (Abeta2-m) deposition
Ligaments, carpal tunnel syndrome, shoulder joints, bone
Glucose 6 phosphate dehydrogenase
Catalyzes initial and RATE LIMITING step of PPP
Deficiency results in hemolytic anemia dt inability to generate NADPH in oxidative portion of pathway.
However, nonoxidative reactions are responsible for conversion of fructose 6 phosphate to ribose 5 phosphate (via TRANSKETOLASE)
Monoclonal antibody treatment mechanism of cell death
ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY
- natural or monoclonal IgG binds to complementary surface antigen on host or foreign cell
- patrolling NATURAL KILLER CELL binds Fc portion of attached IgG via CD16
- binding triggers NK cell to release its granules (PERFORIN, granzymes (proteases) that induce apoptosis/osmotic lysis of ab bound cell
Kawasaki disease
Vasculitis of medium sized arteries
Conjunctivitis
Mucositis
Rash- often perineal area
Distal extremity changes - erythema, edema, DESQUAMATION OF HANDS AND FEET
Cervical LAD
Prolonged HIGH FEVER that does not break with anti pyretics
Strawberry tongue
Feared complication- coronary artery aneurysms
Levetiracetam MOA
Modulates GABA and glutamate release
Binds SV2A to modulate release of GABA and glutamate
To increase pre load
Add volume
Slow HR—> more filling—> more volume
Constrict veins—> veins force blood into heart, veins hold LARGE blood volume, helps maintain CO in setting of blood loss
Cavernous sinus thrombosis
Infection of medial face, sinuses (ethmoidal or sphenoidal) or teeth may spread thru valveless facial venous system into cavernous sinus causes a thrombosis
Pts present with HA, fever, proptosis, I psi lateral deficits in CNs III, IV, VI, V (ophthalmic and maxillary branches)
GPCR and adenylyl cyclase ligands
PTH
ACTH
TSH
ADH V2
Epinephrine
Beta>alpha
INCREASE BP (HIGH DOSES)
INCREASE HR
INCREASE CO
Used in ANAPHYLAXIS, asthma, open angle glaucoma
Alpha effects predominate at HIGH DOSES
Stronger B2 effects than NE
GLUT4
Insulin DEPENDENT
Fat and skeletal muscle
Histoplasma capsulatum
Small intracellular yeasts in MACROPHAGES
Grow in culture as small (2 to 5micron) yeasts with NO CAPSULE
Mississippi Ohio river valley
SLOW ONSET PNA HILAR LAD, CAVITARY PULMONARY LUNG DX, CALCIFIED LN ENLARGED SPLEEN MOUTH ULCERS PANCYTOPENIA
Dx by urine/serum antigen test
Norepinephrine
Alpha1>alpha2>beta1
INCREASE BP
INCREASE HR
No/increase CO
Used in HYPOTENSION, SHOCK
NE increases systolic and diastolic pressure as a result of alpha1 vasoconstriction —> increase MAP—> reflex BRADYCARDIA
Gestational choriocarcinoma
Malignant tumor that arises from trophoblasts
MC preceded by normal pregnancy
Abnormal vaginal bleeding, uterine enlargement, very high bhCG
Composed of anaplastic cytotrophoblasts and syncytiotrophoblasts with no vili
Presents with dyspnea/hemoptysis dt pulmonary mets from hematogenous spread
Clearance calculation
0.7x (Vd/t1/2)
Psoriasis cytokines
IL17 and IL23
Psoriasis - extensor surfaces, silvery plaques
Amphotericin B and nystatin MOA
Binds ergosterol (cell membrane) and leads to pore formation and cell lysis
Heparin lab test
aPTT
Heparin binds antithrombinIII which INACTIVATES thrombin and
IX, X, XI, XII, and plasmin
Prevents progression of existing clots by inhibiting further clotting abs lysis of existing clots relies of endogenous thrombolytics
aPTT measure INTRINSIC and common PATHWAYS
Internal iliac LN drainage
STIs
Cervical cancer
Bladder cancer
Prostate cancer
Aspiration pneumonia
Mouth anaerobes enter lungs
Peptostreptococcus, Fusobacterium, Prevotella
Tx with Clindamycin
Propofol MOA and AE
Highly lipophilic GABA AGONIST used for long term sedation in ICU, RAPID ANESTHESIA INDUCTION
AE- vasodilation that can result in hypotension, INCREASED SERUM TRIGLYCERIDES AND LIPASE
Respiratory depression
Neurotoxins
C tetanus - tetanospasm, prevents release of inhibitory GABA (lockjaw, spastic paralysis)
C botulinum- botulinum toxin, prevents release of stimulatory ACh (flaccid paralysis)
Both inhibit SNARE proteins- neuron can’t release NTs
Huntington dx
AD
CAG trinucleotide repeats on HTT chromosome 4
Degeneration of striatum in basal ganglia (composed of caudate nucleus and putamen)—> chorea and athetosis
Motor cortex provides excitatory input to striatum which regulates voluntary movement based on cortical input
Fluid secretion of GI tract
- Amount of Cl- secreted = amount of water in GI tract. Secretion of Cl- regulated by CFTR
- To increase Cl- secretion, active Gs or AC. CFTR regulated by Gs—> when activated stimulates AC—> increases amount of cAMP inside cell—> activates CFTR to secrete more Cl-. Exotoxins will increase Cl- secretion and therefore the amount of water
Mets to bone
Prostate/breast>kidney, thyroid, lung
Acute intermittent porphyria (5Ps)
Defective heme synthesis that leads to accumulation of heme precursors
PORPHOBILINOGEN DEAMINASE DEFICIENCY
AD, late onset
Accumulation of PORPHOBILINOGEN and ALA
- porphobilinogen and d ALA NEUROTOXIC
—> must test levels during acute attack!
- acute intermittent attacks, only when porphobilinogen high
5 Ps
- Painful abdomen
- Port wine colored pee
- Polyneuropathy
- Psychological disturbances
- Precipitated by P450 inducers, alcohol, starvation, smoking
Treat- HEMIN and GLUCOSE- both blunt heme production—> inhibit d ALA synthase
*30-40yo recurrent unexplained abdominal pain with abnormal urine color and confusion/neuropathy
Methylmalonic acidemia
AR organic acidemia resulting in deficiency of methylmalonyl coA mutase
Results in:
- buildup of METHYLMALONIC ACID and PROPRIONIC ACID—> metabolic acidosis
- HYPOGLYCEMIA dt increased metabolic rate, increased glucose utilization, direct toxic inhibition of gluconeogenesis by organic acids
- hypoglycemia causes increased FFA metabolism—> KETONES in urine
- HYPERAMMONEMIA dt organic acids directly inhibiting urea cycle
Anion gap acidosis, hypoglycemia, ketosis, hyperammonemia
- hypotonia, lethargy, vomiting, respiratory distress
DIAGNOSIS- ELEVATED URINE METHYLMALONIC ACID and PROPIONIC ACID
**normally- catabolism of VOMIT leads to formation of propionyl coA, which is converted to methylmalonyl coA by biotin dept carboxylation—> isomerization via B12 to succinyl coA—> enters TCA cycle
Thayer Martin media (VPN/VCN)
Enriched selective media for Neisseria
Supplemented chocolate agar with:
VANCOMYCIN (kills GP)
COLISTIN (polymyxin) kills GN
NYSTATIN (kills fungi)
Stiff vessels
Low compliance (distensibility) - HTN and elderly
Cardiac primary tumor (kids)
Rhabdomyoma, often seen in tuberous sclerosis
PCN and type IV HSR
T cell mediated
Skin
- EBV pharyngitis - maculopapular rash
- SJS- dermal/epidermal breakdown, fever, necrosis, vesicles
- TEN
Nephritis - drug acts as hapten
- fever, oliguria, increased BUN/Cr, eosinophils in urine, WBCs, WBC CASTS (sterile pyruvate)
IP3 signaling
After ligand binds GPCR that activates phospholipase C, membrane phospholipids broken down to DAG and IP3. Protein kinase C activated by DAG and calcium. Calcium released from ER under IP3 influence
Chronic phenytoin use can cause deficiency of which vitamin?
Vitamin D
- phenytoin induces CYP24, which converts 25 hydroxyvitamin D to inactive form
- result: less 25 hydroxyvitamin D available for conversion to 1,25 di hydroxy vitamin D—> deficiency leads to less intestinal absorption of calcium and compensatory increase in PTH causes release of Ca from bones—> loss of BMD
Smooth ER function
Lipid synthesis
Carbohydrate metabolism
Detoxification
Vancomycin MOA
Binds to terminal D alanine residues of cell wall glycoproteins and prevents transpeptidases from forming cross links
Enzyme that converts alpha keto glutarate to succinyl coA
Alpha ketoglutarate dehydrogenase complex
- thiamine dependent
Familial hypocalciuric hypercalcemia
Benign AUTOSOMAL DOMINANT disorder caused by defective Calcium sensing Receptors (CaSRs) in PARATHYROID GLAND and KIDNEYS
In FHH, higher serum calcium levels are required to suppress PTH—> raises set point of calcium induced regulation of PTH secretion
FHH pts have mild asymptomatic hypercalcemia, reduced urinary excretion of calcium, high/normal PTH
**CaSRs are transmembrane GqPCRs that regulate secretion of PTH in response to circulating calcium levels
Binding of calcium to CaSRs leads to inhibition of PTH release, whereas low calcium levels allow increased PTH release
Developmental field defect
Multiple malformations that occur secondary to embryonic disturbance in adjoining groups of cells
Holoprosencephaly- spectrum of fetal anomalies dt incomplete division of forebrain
Foscarnet MOA and AE
Antiviral medication that inhibits viral DNA polymerase by binding pyrophosphate binding sites
DOES NOT NEED TO BE ACTIVATED BY VURAL KINASE
AE: seizures, HYPOCALCEMIA, nephrotoxic, leukopenia, electrolyte abnormalities
Dobutamine
Sympathomimetic
B1>B2,alpha
INCREASE HR, CO
Used in HF,
cardiogenic shock (inotropic (contractility)>chronotropic(HR))
Cardiac stress testing
Sarcoplasmic reticulum Ca2+ ATPase (SERCA)
SERCA removes Ca2+ from sarcoplasm and sequesters Ca in sarcoplasmic reticulum. Allows myocyte to relax.
SERCA is inhibited by PHOSPHOLAMBAN
In exercise—> Beta adrenergic stimulation by SNS phosphorylase phospholamban, allows SERCA to take up Ca more vigorously —> more rapid and vigorous relaxation (higher lusitropy)—> more preload
Hypertrophic scars
Excess formation of ORGANIZED extracellular matrix
Protrude above surface of the skin but are confined to the original wound margins
Bilateral ovarian metastases from gastric carcinoma
Krukenberg tumor (mucin secreting signet ring cells)
Right cardinal vein
SVC
Central nausea (migraines) anti emetics
Dopamine antagonists (metoclopromide, prochlorpermazine) - treat cent nausea and reduce migraine HA pain
AE- sedation, extrapyramidal symptoms
Pulmonary HTN and advanced hypoxic lung disease (COPD, interstitial lung disease, obesity hypoventilation syndrome) mechanism
Hypoxic vasoconstriction is a physiologic mechanism unique to lung tissue that helps minimize ventilation perfusion mismatch and increases overall gas exchange efficiency
However, chronic and diffuse pulmonary vasoconstriction, which occurs in advanced hypoxic lung disease can lead to pulmonary HTN (ie increased RV afterload)
Dyspnea, fatigue, left parasternal shift (from RVH) and loud S2 dt high pulmonary artery pressure. Overtime, RV may be unable to pump against resistance from lunch’s—> RHF and edema, JVD
De Quervain thyroiditis
Self limited dx OFTEN FOLLOWING FLU LIKE ILLNESS (viral infection)
Maybe hyperthyroid early followed by hypothyroid
Histology: granulomatous inflammation
Findings: HIGH ESR, JAW PAIN, VERY TENDER THYROID
TNFa
Can cause vascular leak, septic shock
Cachectin- inhibits lipoprotein lipase in fat tissue—> reduces utilization of FAs—> cachexia
Increases synthesis of endothelial adhesion molecules—> allows neutrophils to enter inflamed tissue
Can cause DIC- coagulation and thrombosis in vasculature of tumor
Macrophage secreted
Ankylosing spondylitis
Altered gut biome/defective mucosal barrier
INCREASED IL17, TNF alpha, PROSTAGLANDINS
Increased risk with HLAB27
Inflammatory back and buttock pain, reduced chest expansion and spinal motility,
Thiamine (B1) cofactor for which 4 reactions? (Be APT)
DECARBOXYLASE RXNS
Branched chain ketoacid dehydrogenase
Alpha ketoglutarate dehydrogenase (TCA)
Pyruvate dehydrogenase (links glycolysis with TCA)
Transketolase (HMP shunt)
Carbamoyl phosphate synthetase I deficiency
High ammonia, hyperammonemia
Increased blood glutamine
BUN decreased
NO OROTIC ACIDURIA
AR
CEREBRAL EDEMA, lethargy, coma, death
Patent urachus
Complete failure of obliteration of the urachus (connection between bladder and umbilicus)
Straw colored urine discharge from umbilicus, gets worse with crying, proning, straining
Local skin irritation
SIADH
Small cell carcinoma of lung
Ureteric bud
Gives rise to
Collecting system of kidney
- collecting tubules and ducts
- major and minor calyces
- renal pelvis
- ureters
TATAAA box
Promoter region
Located directly upstream from a gene
Upper midbrain contains
Neural structures (optic nerve, pretectal nuclei, and Edinger Westphal nuclei, oculomotor nerve) that mediate direct and consensual pupillary light reflex
Congenital adrenal hyperplasia
21 hydroxylase deficiency
- it’s cannot convert 17- hydroxyprogesterone to 11 deoxycortisol
- therefore reduced cortisol and aldosterone synthesis and elevated 17 hydroxyprogesterone
- corticosteroid precursors accumulate and diverted to excess adrenal androgen production
- low cortisol leads to high ACTH
Girls at birth have ambiguous genitalia (virilization) dt excess androgens. Boys have normal genitalia and are identified at 1-2 weeks with vomiting, hypotension, hyponatremia, hyperkalemia dt lack of mineralcorticoids
Cortisol deficiency causes hypoglycemia and impairs ability to maintain BP
Abdominal abscesses/perforations
Bacteroides fragilis (anaerobe)
Treat with Metronidazole
Metanephros (5)
Gives rise to
GLOMERULI BOWMANS CAPSULE PCT LOOP OF HENLE DCT
Blastomyces dermatitidis
Dimorphism fungi that can cause pulmonary infections in IMMUNE COMPETENT PEOPLE
Exists in mold in soil, organic matter, animals
Transmitted respiratory route, inhaled and transforms to yeast
BROAD BASED BUDDING
May be asymptomatic or mimic PNA
GRANULOMAS FORMATION
Extrapulmonary disease in immunopromised
Subclavian steal syndrome
Occurs dt hemodynamicat significant stenosis of
t(14;18)
Follicular lymphoma (BCL2 activation, anti apoptotic oncogene)
Penicillin MOA
PCN binds bacterial transpeptidases
Mimics d ala- d ala—> INACTIVATES ENZYMES
Wall breakdown>wall creation—> autolysis
Anterior shoulder dislocation
Flattening of deltoid muscle with acromion prominence after shoulder injury
Axillary nerve injury—> deltoid paralysis and loss of sensation over lateral shoulder
MC occurs to externally rotated, abducted arm (throwing football)
Leiomyomas
Uterine fibroids
Benign myometrial smooth muscle cell tumors
Heavy menses
Uterus is NONTENDER and IRREGULARLY SHAPED
JAK STAT signaling ligands
Insulin Growth hormone Cytokines (interferon) Hematopoietic growth factors (EPO, GCSF) MAP kinase
Aortic regurgitation LV pressure findings
Decreased diastolic BP
Increased LVEDP
Aortic regurgitation can be a complication of Transcatheter Aortic Valve Implantation (TAVI) from improper sealing of prosthetic valve to native annulus—> paravalvular leak
TAVI also risks stroke, MI
HPV associated with genital warts
HPV 6 and 11
Predilection for stratified squamous epithelium—> anal canal, vagina, cervix, and TRUE VOCAL CORDS
- infants can acquire respiratory papillomatosis via passage through infected birth canal
- warty growths on true vocal cords—> weak cry, hoarseness, stridor
Ataxia telangiectasia triad
Cerebellar atrophy
Spider angiomas
IgA deficiency
Mutation in ATM gene- mutation in NHEJ and serine/threonine kinase involved in V(D)J Recombination - major mechanism for ab and lymphocyte diversity
Pts also have high AFP
Pulmonary actinomyces
Develops dt aspiration
Can be confused with lung abscess, malignancy, Tb
Microscopy shows filamentpus, branching, gram + bacteria and SULFUR GRANULES (turn purple on H&E)
Actinomyces colonizers mouth, colon, vagina and can be found in cavities and margins of gums with poor dentition
Actinomyces infection MC leads to cervicofacial abscesses, can have lung involvement
Alcoholics at risk. Tx with PCN G
Neutrophil small granules
Alkaline phosphatase, collagenase, lysozyme, lactoferrin
Fuse with phagosome to kill pathogens AND can be released into extra cellular space
Specific/secondary
Cutaneous T cell lymphoma
Skin disorder of malignant T cells
Variable expression of CD markers
PRESENTS WITH SKIN LESIONS
- localized dx: Mycosis fungoides
- diffuse systemic dx: Sezary syndrome
Indole positivity
Ability to convert tryptophan to indole—> distinguishes E coli from Enterobacter cloaca, both common pathogens for UTIs in women
Retroperitoneal structures SAD PUCKER
Supra Adrenals
Aorta and IVC
Duodenum (2nd- 4th parts)
Pancreas (head and tail) Ureters Colon (descending and ascending) Kidneys Esophagus (thoracic portion) Rectum (partial)
Etomidate MOA and AE
GABA AGONIST
Rapid induction of anesthesia, short acting
HEMODYNAMICALLY NEUTRAL- does not change HR, CO, BP
Inhibits cortisol synthesis—> reversible adrenocortical suppression
AVOID IN PTS WITH SEPTIC SHOCK
PCN and type I HSR
Acute
IgE mediated
Anaphylaxis
Nucleotide excision repair
Repairs UV damage—> repairs bulky pyrimidine dimers
Defective in XERODERMA PIGMENTOSA
- defective nucleotide excision repair in skin cells
- extreme sensitivity to UV light
- s/s appears in infancy/childhood
- easy sunburning, dry skin, HIGH RISK FOR SKIN CANCER
Thoracic duct drains what part of body?
Left upper extremity Left side of head Neck Chest Body below diaphragm
Drains into left subclavian vein
Astrocyte stain
GFAP
Aortic regurgitation on cardiac cath
LARGE PULSE PRESSURE
Loss of aortic dicrotic notch
Steep diastolic decline of aortic pressure
Murmur best heard with patient leaning forward and right after aortic valve closes (pressure gradient between aorta and LV greatest)
Most common mutation in familial dilated cardiomyopathy
AUTOSOMAL DOMINANT mutations in TTN gene (titin- sarcomere protein)
Hereditary harmless jaundice
Gilbert syndrome (benign congenital unconjugated hyperbilirubinemia)
Macrolide abx MOA
Bind 50s ribosome at P site at 23S rRNA—> block translocation
Inhibit protein synthesis
Azithromycin, Clarithromycin, Erythromycin
Used for intracellular infections- atypical PNA, chlamydia, B pertussis, GP infection in PCN allergic pts
AE: Motility issues (GI) Arrhythmias (QT PROLONGATION) Cholestatic hepatitis Rash Eosinophilia
INCREASES THEOPHYLLINE AND WARFARIN LEVELS
- clarithromycin and erythromycin INHIBIT P450
Maple syrup urine disease
Blocked degradation of BRANCHED CHAIN AMINO ACIDS (ISOLEUCINE, LEUCINE, VALINE) dt decreased branched chain alpha keto acid dehydrogenase —> causes high alpha keto acids in blood, ESPECIALLY LEUCINE
AUTOSOMAL RECESSIVE
Leucine is neurotoxic—> SEVERE CNS DEFECTS, MR, death. Urine smells like burnt sugar
Tx: dietary restriction of ISOLEUCINE, LYSINE, LEUCINE
Actinomyces israelii
Normal oral, reproductive, GI flora
Causes oral/facial abscesses that drain thru sinus tract
Can cause PID from IUD
Methotrexate induced lung injury
Weeks/months low dose MTX therapy
Usually hypersensitivity reaction—> eosinophils and lymphocytes
Can progress to pulmonary fibrosis if MTX not discontinued
Right horn of sinus venosus
Smooth part of RA
Heparin induced thrombocytopenia (HIT) type 2
Heparin induces conformational change in platelet factor 4–> formation of neoantigen
IgG abs form against heparin-platelet factor 4—> abs aggregation on platelet surface
5-10 days after heparin start
Thrombocytopenia is hallmark feature dt clearance of antibody coated platelets by splenic macrophages
Antibody aggregation on platelets cause platelet aggregation—> worsens thrombocytopenia and increases risk of DVT
TREATMENT- stop heparin and start argatroban/bivalrudin
Mallory bodies
Classic finding in alcoholic liver disease
Intracytoplasmic eosinophilic inclusions of damaged keratin filaments
Ok bx: swollen and necrotic hepatocytes with neutrophilic inflammation and Mallory bodies
Pathognomonic finding for pyelonephritis in setting of UTI
WBC casts
Can also be seen with acute interstitial nephritis (fever, AKI symptoms, no urinary symptoms)
Aldesleukin
IL2 used for renal cell carcinoma and melanoma
Thought to work because activates NK cells
Dysplasia
Disordered proliferation
Mild dysplasia may resolve
Usually occurs in epithelial cells
Usually preceded by hyperplasia, metaplasia
CD4 T cells
Helper T cells
Produce cytokines
Activate other cells
DIRECT IMMUNE RESPONSE
Mesonephros in FEMALES
Mesonephros regresses and becomes vestigial Gardner’s ducts
ERBB1 (EGFR) proto oncogene
Receptor tyrosine kinase
Lung adenocarcinoma
Glimepride
Second generation sulfonylurea that undergoes hepatic clearance and is safer to use in patients with RENAL DYSFUNCTION and heart failure than metformin
MOA- insulin secretogogue that blocks K channels in pancreatic beta cells—> cell depolarization and Ca influx—> INSULIN RELEASE
Metabolized by LIVER and safer to use in HF and RENAL FAILURE
METFORMIN SHOULD NOT BE USED IN RENAL INSUFFICIENCY, HF, CONDITIONS THAT PREDISPOSE PTS TO HYPOXEMIA OR LACTIC ACIDOSIS
Wiskott Aldrich syndrome
Thrombocytopenia
Eczema
Immunodeficiency
Defective protein WASp- participates in reorganization of hematopoietic cell cytoskeleton in response to stimuli —> WAS pts cells cannot migrate in response to normal stimuli
ELEVATED IGA AND IGE, no IgM
X linked recessive, young boys
- hepatosplenomegaly
- thrombocytopenia
- recurrent infections
- eczema
High risk of lymphoid malignancies
Radial nerve
C5-T1
Sensory innervation to skin of posterior arm, forearm, dorsolateral hand
Motor innervation to ALL EXTENSOR MUSCLES OF UPPER LIMB BELOW SHOULDER
Axilla or midshaft humerus injury—> wrist drop
Phenylephrine
Alpha1>alpha2
Increase BP (vasoconstriction) LOWER HR
Used in HYPOTENSION (vasoconstrictor)
Mydriatic ocular procedures
Rhinitis (decongestant)
Ischemic priapism
Thymic aplasia aka DiGeorge syndrome
22q11 deletion
Triad- loss of thymus (recurrent infections, no T cells), loss of parathyroid glands (hypocalcemia, tetany), congenital heart defects (upper part of heart—>contonotruncal= abnormal aortic arch, truncus arteriosus, TOF, ASD/VSD)
Failure of third and fourth pharyngeal pouches
Viral, fungal, protozoal infections, intracellular bacterial infections
Absent of thymic shadow on CXR
Cleft palate and mandible problems also common
Fidaxomicin
Inhibits sigma unit of RNA polymerase—> inhibits C diff protein synthesis
Oral
Macrocyclic abx (related to macrolides)
Human granulocytic anaplasmosis
Caused by Anaplasma phagocytophilum
Intracellular bacteria transmitted by Ixodes tick (which also transmits Lyme (Borrelia burgdorfei) and Babesia microti
Presents with influenza like symptoms and no rash
PATHOGNOMONIC FEATURE: morulae (berry like clusters of organisms) inside pts granulocytes
Tx with DOXYCYCLINE
Multiple sclerosis
Demyelinating disease in young women
Isolated systolic HTN in elderly pts
Common aging process
Results from AGE RELATED STIFFENING (replacement of elastin with collagen) and REDUCED COMPLIANCE OF AORTA/ large arteries
CV changes in elderly-
- Aortic stiffening- elastin replaced with collagen, high pulse pressure (isolated SBP HTN)
- Mild concentric LVH- higher after load, lower CO
- Conduction cell degeneration - lower resting HR and maximal HR
- Reduced baroreceptor sensitivity and adrenergic responsiveness (orthostasis, lowered HR and contractility)
Tay Sachs
Deficiency of lysosomal hexosaminidase A
Accumulation of ganglioside GM2 (sphingolipid) in lysosomes of CNS and retina
- cherry red spot on macula
- dilated neurons with lipid filled vacuoles in CNS
- normal at birth, progressive loss of motor, vision, hearing
- intellectual ability
- EXAGGERATED STARTLE REFLEX
AUTOSOMAL RECESSIVE
NO HEPATOMEGALY NO SPLENOMEGAL
What do T cells recognize
PEPTIDES ONLY
Rheumatic fever
TYPE II HSR
Aschoff bodies- cardiac modules with inflammatory cell (granulomas)
Anitschkow cells- macrophage with owl eye appearance
ELEVATED ASO TITERS
Joint pain (polyarthralgia) Carditis Nodules (subQ) Erythema marginatum Sydenham chorea - sore throat or URI with joint pain, new murmur - 2 types cardiac involvement: 1. Acute RF: severe valve disease, HF 2. Later: mitral stenosis (rare aortic or tricuspid)
Hodgkin lymphoma
Malignant cell: REED STERNBERG CELL
- minority of cells in enlarged LNs
- release cytokines—> generate REACTIVE CELLS
Majority are REACTIVE CELLS
- majority of cells in LN
- B symptoms common (MC than in non Hodgkin lymphoma)
- can lead to HYPERCALCEMIA
- macrophages get activated—> contain 1alpha hydroxylase —> excess vitamin D—> hypercalcemia
Arterial supply to 1. Distal lesser curvature of stomach and 2. Proximal lesser curve
- Right gastric supplies distal lesser curve
2. Left gastric supplies proximal lesser curve
Loading dose
[steady state]x(Vd/F)
T cell leukemia/lymphoma
CD4 T cell malignancy
Occurs with HTLV1 infection (RNA virus, infects CD4 T cells)
Key diagnostic test- anti HTLV1 abs
Pts from JAPAN, Caribbean, West Africa (endemic regions):
- LAD
- LYMPHOCYTOSIS
- SKIN LESIONS
SKIN LESIONS (ulcers, nodules, papular rash) Rapidly progressive
LYTIC BONE LESIONS w HIGH CALCIUM
Klinefelter syndrome
Caused by meiotic non disjunction resulting in 47XXY, 46XY/47XXY mosaicism, or 48XXXY—> more Xs, more severe manifestations
Diagnosed at puberty when characteristic signs develop
- Primary testicular failure dt hyalinization and fibrosis of seminiferous tubules. SMALL FIRM TESTES AND AZOOSPERMIA (infertility)
Leydig cell dysfunction also occurs abs leads to testosterone deficiency. LH and FSH are increased secondarily to gonadal failure - Testosterone deficiency results in development of euchanoid body habitus. Tall stature, gynecomastia. Facial and body hair is sparse/absent and low muscle mass
- Mild MR
Pindolol/acebutolol
Partial agonists
Acebutolol (b1>b2)
Pindolol (b1=b2)
Intrinsic sympathomimetic activity
- beta AGONIST when SNS activity low
- beta BLOCKER when SNS activity high
Can cause ANGINA dt b1 activation
Gastric erosion vs ulcer
Erosion SHALLOWER than ulcer
Ulcers involve damage to gastric mucosa beyond muscularis mucosa and into the submucosa
Cryptococcus neoformans meningitis
Immunosuppressed (low CD4) pts with fungal meningitis
BUDDING ENCAPSULATED YEAST ACQUIRED FROM PIGEON DROPPINGS AND UREASE POSITIVE
Not dimorphism, hematogenous spread to meninges
Dx via latex agglutination of CSF or India ink (halo), mucicarmine stain
ELEVATED OPENING PRESSURE WITH LP
Amphotericin b + flycytosine followed by fluconazole
Astrocyte stain
GFAP
Amitryptiline use in polyneuropathy
Modulates pain transmission by INHIBITING VG NA CHANNELS in sensory nerves, blocks NMDA (excitatory) receptors in spinal cord and alter NE signaling in brain
Small intestine bacterial overgrowth
Increased production of FOLIC ACID and VITAMIN K
Deficiency of B12, A, D, E, and IRON
Henoch Schonlein purpura (IgA vasculitis)
Palpable purpura, abdominal pain, arthralgia, renal involvement
Leukocytoclastic vasculitis- damage to SMALL blood vessels with fibrinoid necrosis, peri vascular neutrophilic inflammation
IF shows IgA and C3 deposition
Aromatase
Key enzyme in estrogen synthesis
Aromatase converts androstenedione to estrone and testosterone to estradiol
Aromatase deficiency is AR characterized by high androgen and low estrogen.
Newborn girls with aromatase deficiency have normal internal genitalia but AMBIGUOUS EXTERNAL GENITALIA. Mother’s can develop virilization from excess androgens spilling from fetus to mother through placenta
PDGF effects
Stimulates cells from G1 to S
Binds tyrosine kinase
PDGF released at atherosclerotic lesions by platelets, macrophages and stimulates proliferation and migration of smooth muscle cells in tunica intima in response to endothelial injury
Mediates differentiation of fibroblasts into myofibroblasts- necessary for fibrous cap formation
Cardiac output 2 formulas
Cardiac output = SV x HR
Cardiac output= rate of O2 consumption/ arteriovenous O2 content difference
Neutrophil larger granules
Acid phosphatase, myeloperoxidase
Fuse with phagosome ONLY
Primary or azurophillic
HPV
Associated with cervical cancer
Expresses HPV oncogene E6–> leads to synthesis of E6 protein
E6 protein binds p53–> p53 degradation
Degradation via ubiquitination—> p53 binds to ubiquitous—> targets protein for degradation in proteosomes
Flutamide
Competitive antagonist at androgen receptors
Non steroidal anti androgen
Used to treat prostate cancer
Decreased endogenous androgen activity —> inhibits tumor growth and may contribute to tumor regression
Hydralazine
Direct ARTERIOLAR VASODILATOR
- reduces afterload
Increased cGMP—> smooth muscle relaxation
Admin with beta blocker to prevent reflex tachycardia
Tricuspid regurgitation
Holosystolic murmur that increases in intensity with INSPIRATION
Loudest at left sternal border at second or third intercostal space
Neuroblastoma
Common malignancy in chemistry under 5
Arises from NCC that populate adrenal medulla and sympathetic chain
Mutation in tumor suppressor, MYCN
- poor prognosis
ASYMPTOMATIC ABDOMINAL MASS CROSSING MIDLINE
Histo- small blue cells forming Homer Wright peudorosettes (rings of tumor cells that surround tumor nerve fibers)
Toll like receptors
INNATE IS
Key receptors on macrophages, dendritic cells, mast cells
Recognize PAMPs (LPS, flagellin, nucleic acids) and DAMPs. Leads to activation of NfKB
Niemann Pick disease
AR lysosomal storage dx
Caused by deficiency of sphingomyelinase—> breaks down sphingomyelin (phospholipid) to ceramide
Excess sphingomyelin results in lipid laden foam cells that accumulate in LIVER, SPLEEN, CNS—> hepatosplenomegaly and hypotonia and neurodegeneration AND retinal opacification (cherry red spot on macula)
Cryptococcus neoformans
Acquired via inhalation with hematogenous spread to MENINGES
Highlighted with INDIA INK, MUCOCARMINE (red inner capsule), LATEX AGGLUTINATION detects polysaccharide antigen
Causes cryptococcosis, cryptococcal meningitis, cryptococcal encephalitis (soap bubble lesions in brain) IN IMMUNOCOMPROMISED PEOPLE
tx: amphotericin b + flucytosine followed by fluconazole for meningitis
Femoral nerve injury
Nerve roots L2 to L4
Injury dt pelvic fracture, mass involving iliopsoas/iliacus muscles (hematoma, abscess), injury during surgery or childbirth
Impaired flexion of thigh and extension of leg
Findings:
- quadriceps weakness(difficulty with stairs, knee buckling)
- Decreased patellar reflex
- Sensory loss over anterior and middle thigh/leg
Midodrine
Alpha1
INCREASE BP (vasoconstriction) Lowers HR, lowered CO
Used for AUTONOMIC INSUFFICIENCY and POSTURAL HYPOTENSION
May exacerbate supine HTN
MGUS
Asymptomatic plasma cell disorder
Abnormal SPEP (presence of M protein)
No end organ damage
Can progress to multiple myeloma
No CRAB findings
First order elimination
Rate varies with drug concentration
% change with time is constant (half life)
Most drugs
FLOW DEPT ELIMINATION
Medullary thyroid carcinoma
Arises from PARAFOLLICULAR C CELLS (which produce calcitonin)
Calcitonins precursor proteins can precipitate and form amyloid deposits that appear as AMORPHOUS PROTEINACEOUS material on FNA
Methenamine silver stain
Stains Pneumocystis jirovecii- atypical, extracellular monomorphic (yeast like)
Saucer shaped cysts on microscopy
P. jirovecii causes DIFFUSE B/L INTERSTITIAL PNA AND SEVERE HYPOXIA
AIDS defining illness
Tx/prophylaxis: TMP SMX, PENTAMIDINE, dapsone, atovaquone
Start prophylaxis when CD4 count <200
Astrocyte diseases (2)
Astrocytomas- cerebellum of children (GFAP +)
JC virus infects astrocytes and oligodendrocytes
- causes PML in HIV pts
Secondary amyloidosis
Chronic infection
Chronic inflammation
Serum amyloid A—> increased production—> amyloid A (AA) deposition
Kidney, liver, spleen, heart, peripheral nerves, tongue, skin
Sumatriptan
5HT1b/1d AGONIST indicates for treatment of acute migraine attacks
HYPERTENSIVE CRISIS AND MI are potential side effects of sumatriptan
Contraindicated in pts with poorly controlled HTN or MI
Scalded skin syndrome
Newborn disease, seen in adults with renal insufficiency
Colonization of skin with S AUREUS
Diffuse exfoliative toxin
Fever, diffuse erythema, sloughing of upper layer of epidermis
HEALS COMPLETELY WITH NO SCAR
+ Nikolsky sign, treat w abx
Fabrey disease
X LINKED RECESSIVE
Lysosomal storage disease resulting from hereditary deficiency of ALPHA GALACTOSIDASE A—> intracellular accumulation of GLOBOTRIAOSYLCERAMIDE
Kidneys, heart, nervous system, eyes commonly affected
- URINARY FAT BODIES from ceramide in urine
Triad- episodic peripheral neuropathy, angiokeratomas, hypohydrosis
Later in life- renal failure, CV disease
Anemia and blood oxygen content
Anemia decreases the oxygen content of arterial blood because the vast majority of oxygen is transported in blood bound to Hb—> anemia reduces Hb content of blood and thereby REDUCES OXYGEN CARRYING CAPACITY
- this limits how much oxygen can be delivered to tissues, so while arterial blood entering a vascular bed will have a normal O2 saturation
—> blood exiting vascular bed will have a reduced O2 saturation compared to
Normal AND the venous PO2 will also be lower
OXYGEN CARRYING CAPACITY OF BLOOD IS PROPORTIONAL TO RBC NUMBERS (Hct) and Hb
Non anion gap metabolic acidosis
“Hyperchloremic acidosis”
- inverse relationship between bicarbonate and Cl
Hyperalimentation Addisons RTA Diarrhea Acetazolamide Spironolactone Saline infusion
Spleen position in abdomen
Upper left quadrant
Deep to ribs 9,10,11
Primary regulator of adrenal zona glomerulosa (aldosterone)
ANGIOTENSIN II
Benzodiazepines and phenobarbital MOA
Increase GABAa action
Bind GABA receptors a d all increased Cl current thru ion channel. Hyperpolarizes cell membrane, which increases threshold of excitability of post synaptic neuron
Heterophile negative virus
CMV
EBV- heterophile +
Tricyclic antidepressants (amitriptyline, imipramine, nortripyline, desipramine)
Inhibit NE and 5HT reuptake
MAJOR SIDE EFFECTS:
1. Anti muscarinic effects- dry eyes, dry mouth, tachycardia, urinary retention, sedation, constipation
- Alpha adrenergic block- orthostatic hypotension
- QT prolongation, Tdp, AV block
- TCAs have broad receptor effects
Fibrillin
Large EXTRACELLULAR MATRIX PROTEIN
Calcineurin inhibitors (tacrolimus, cyclosporine)
Block translocation of NFAT (nuclear factor of activated T cells)—> reduced IL2 transcription
Follicular lymphoma
Subtype of non Hodgkin’s lymphoma
B cell malignancy
OVER EXPRESSION OF BCL2–> mitochondrial pores will not open, caspases cannot activate—> cell will not undergo apoptosis—> uncontrolled cell growth
t(14;18)
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
Lead poisoning/intoxication
Lead affects AMINOLEVULINATE (ALA) DEHYDRATASE and FERROCHELATASE in heme pathway—> low heme synthesis and high RBC protoporphyrin —> microcytic hypochromic anemia
Also inhibits rRNA degradation—> RBCs retain aggregates of rRNA (basophilic stippling)
S/s:
- lead lines on gingivae, metaphysis of long bones
- encephalopathy and erythrocyte basophilic stippling
- abdominal colic and sideroblastic anemia
- wrist drop and foot drop, demyelination
Iron studies can be low/normal
Tx- DIMERCAPROL and EDTA, use SUCCIMER for chelation in kids
PCNs and cephalosporin MOA
Irreversibly bind to penicillin binding proteins (transpeptidases)
Th17 cells
Subset of CD4
Produce IL17
Important for mucosal immunity in GIT
Loss of Th17 cells shows GI bacteria in blood stream
Recruit neutrophils and macrophages
Retinitis pigmentosa
Genetic condition resulting in progressive dystrophy of retinal pigmented epithelium and photoreceptors
Progressive night blindness, loss of peripheral vision dt early loss of rods (very metabolically active)
Exam shows dark pigments deposited in bone spicule pattern and retinal vessel attenuation and optic disc pallor
Hamartomas
Lesions composed of tissue types that are native to the organ of involvement but show abnormal disorganized arrangement
Benign neoplastic lesions
Verapamil
NON DHP CCB
Inhibits L type calcium channels in the heart
NEGATIVE INOTROPIC EFFECT—> reduced contractility, can exacerbate symptoms of HF
Nucleolus
Site of ribosomal subunit maturation and assembly
RNA POL I functions exclusively within nucleolus to transcribe rRNA
Vitamin E deficiency
HEMOLYTIC ANEMIA (vitamin E protects RBCs membranes from free radical damage)
MUSCLE WEAKNESS
DEMYELINATION OF POSTERIOR COLUMNS
(Decreased position and vibration sensation) and SPINOCEREBELLAR TRACT (ataxia)
HEMOLYTIC ANEMIA and MUSCLE WEAKNESS , DIPLOPIA
Neuro presentation may appear solitary to B12 deficiency but NO megaloblastic anemia, hypersegmented or high MMA
B Pertussis infection
Infection causes hyperreactivity of respiratory apparatus
Produces PERTUSSIS TOXIN (A and B)—> ADP ribosylates Gi—> inhibits negative regulator of adenylate cyclase—> increaseS cAMP
S/s:
- increased insulin production—> HYPOGLYCEMIA
- lymphocytosis
- blockade of immune effector cells
- increased histamine sensitivity
Grown on Bordet Gengou agar
Fluorescent abs verifies dx
Chronic lymphocytic leukemia
Disorder of naive lymphocytes
CD5+, CD20+, CD23+ B CELLS
MC adult leukemia (60yo)
Asymptomatic, LAD, splenomegaly, hepatomegaly
Observed without treatment
SMUDGE CELLS- peripheral lymphocytes are fragile, membranes crushed during prep
B cell disruption—> HYPOGAMMAGLOBULINEMIA- low Igs therefore HIGH INFECTION SUSCEPTIBILITY
Autoimmune hemolytic anemia typically develops
Disseminated intravascular coagulation
Diffuse activation of clotting factors
- consumption coagulopathy
Prolonged PT/PTT Thrombocytopenia Vascular occlusion - microangiopathic hemolytic anemia - ischemic tissue damage
Can present as bleeding
IP3 hormone messaging (GOAT HAG)
GnRH OXYTOCIN ADH V1 TRH HISTAMINE H1 ANGIOTENSIN II GASTRIN
M protein
Expressed by GAS
Surface molecules on bacteria
M protein prevents phagocytosis by binding factor H and breaks down C3 convertase —> prevents formation of C3b (prevents opsonization)
Shares properties with myosin—> may be basis for rheumatic heart disease And post strep complications
- rheumatic heart disease
- glomerulonephritis
Different M protein subtypes associated with each complication.
NK Cell surface molecules
CD16- binds Fc of IgG—> enhanced activity of NK cells, antibody dependent cell mediated cytotoxicity
CD56- marker for NK cells
Metabolism of EtOH
EtOH metabolized by alcohol dehydrogenase and aldehyde dehydrogenase—> reduces NAD+ to NADH—> increases NADH/NAD+ ratio
This inhibits all other pathways requiring NAD+, including gluconeogenesis
- lactate cannot be converted to pyruvate, which forces pyruvate to lactate
Excess NADH inhibits conversion of malate to OAA
Both pyruvate and OAA are intermediates in gluconeogenesis; therefore conversion of these molecules to lactate and malate inhibits gluconeogenesis
Hypoglycemia once hepatic glycogen stores depleted
Stress incontinence
Decreased urethral sphincter tone, urethral hyper mobility
Leakage with coughing, sneezing, lifting
Ethylene glycol and methanol intoxication treatment
Fomepizole
Inhibits alcohol dehydrogenase and prevents formation of toxic metabolites
EtOH competitive inhibitor of alcohol dehydrogenase and can also be used in toxicity
Post streptococcal GN
Nephritic syndrome 2-3 weeks after GAS infection
Nephritogenic strains- bacteria with certain M protein subtypes cause nephritis
Astrocyte diseases (2)
Astrocytomas- cerebellum of children (GFAP +)
JC virus infects astrocytes and oligodendrocytes
- causes PML in HIV pts
Potter sequence
Flattened facies
Limb deformities
Pulmonary hyposplasia
Caused by oligohydramnios
High mortality
MDD atypical features
Increased appetite and sleep
Leaden paralysis
Rejection sensitivity
Mood reactivity
MAOIs used in patients with treatment resistant MDD with atypical features (phenelzine, tranylcypromine)
Cystic degeneration of the putamen
Wilson’s disease
Inhibin B in men
Produced by Sertoli cells and is the physiologic inhibitor of FSH
Sertoli cells present in seminiferous tubules of testes
First generation H1 blockers
Diphenhydramine
Promethamine
Chlorpheniramine
Hydroxyzine
Cause significant sedation, especially when used with benzodiazepines (ie diazepam- long acting benzo)
Easily penetrate CNS and accumulate
LV characteristics
High muscle mass High resting oxygen extraction Coronary perfusion DIASTOLE ONLY Less developed collateral circulation Low ischemic pre conditioning
Diazoxide
Diazoxide is a potassium channel activator that opens potassium channels → potassium efflux from insulin-producing β cells → hyperpolarization of the cell membrane → negative membrane potential that inactivates and closes voltage-gated calcium channels → decreased influx of calcium into pancreatic cells → drop in intracellular calcium concentration → decreased exocytosis of insulin granules (side effects include sodium retention, edema, hirsutism, and hyperkalemia)
Also used in hypertensive emergency—> K channel activation relaxes arteriolar smooth muscles cells and causes vasodilation
Cardiac myxomas
MC cardiac tumor in adults - mucoid, gelatinous hypo cellular
Generate in LEFT ATRIUM
Benign, mesenchymal origin
Cause syncope dt mitral valve outflow obstruction and thromboembolic events
Severe anemia causes (4)
- Increased arteriolar diameter (reflex vasodilation) which results in decreased SVR
- arteriolar diameter increases reflexively in pts with tissue hypoxia. Vasodilation in response to decrease PO2 is homeostatic mechanism facilitate increased increased blood flow to hypoxic areas - Decreased tissue oxygen tension (anemic hypoxia)
- Decreased blood viscosity
- Decreased splanchnic flow
Bacterial meningitis in adults and elderly
S pneumoniae
PCN resistance (3)
- Modified PBPs
- genetic mutations - Reduced bacterial cell penetration.
- Beta lactamases
- in periplasm of GN, GP secrete into extracellular space
Field cancerization
Large area of cells within a field (upper aerodigestive tract) that are “primed” to develop cancer because of widespread exposure to mutagens (tobacco)
Even with adequate treatment of malignancy, these areas affected by field cancerization remain at higher risk of developing multiple primary malignancies
Auto regulation of renal blood flow is mainly effected by
AFFERENT ARTERIOLAR CONSTRICTION
Auto regulation is a property of all vascular beds. In kidney, 2 mechanisms:
- Myogenic response
- vascular smooth muscle cells contract reflexively in response to rising wall tension caused by increasing perfusion pressure. Contraction decreases RBF. Rapid and accounts for 40-55% of auto regulation - Tubuloomerular feedback.
- when SBP arises, GFR rises which increases NaCl delivery to macular densa. They respond by releasing adenosine and ATP to stimulate contraction of afferent arteriole
Efferent arteriole does not contribute to auto regulation of RBF, but it’s constriction helps maintain stable GFR at low perfusion
Third pharyngeal pouch gives rise to
Inferior parathyroid gland and thymus
MAOI medications (3)
Phenelzine
Trancyclomine
Isocarboxazid
- GI and hepatic MAO inhibited by MAOIs and allow large quantities of tyramine to reach systemic circulation
Tyramine enters synaptic terminals and displaces massive amounts of NE from the —> sympathetic crisis and HTN emergency
Antidote for serotonin syndrome
CYPROHEPTADINE
- anti histamine and non specific serotonin antagonist
TGFb and IL10
Attenuate immune response
Chronic atopic dermatitis (eczema)
Inflammatory condition that begins in infancy/childhood and flares with low humidity (winter months) or excessive heat
FAMILY HX OF ATOPIC DX- asthma, allergies, allergic rhinitis
HIGH IgE
Genetically mediated epidermal barrier dysfunction - loss of FILAGGRIN
- loss of epidermal water content
- increased permeability to environmental allergens/irritants
- skin inflammation
- IL4 and IL13 mediated (IL4 produces IgE)
- Th2 predominate immune response (IL4/13 Th2 cytokines)
Itchy, dry, erythematous papules/vesicles
Infants- face, adults- flexor surfaces
Histology- T cell, mast cell, eosinophil infiltration
Flexor surfaces
Chronic lesions show epidermal thickening dt repetitive scratching
Manic episode DIGFAST
Distractingly
Impulsive
Grandiosity
Flight of ideas
Activity is high
Sleep not needed
Talkative, pressured speech
Class III anti arrhythmics (AIDS)
Amiodarone
Ibutilide
Sotalol
Dofetilide
Block K channels and inhibit outward K currents in phase 3 of cardiac action potential —> prolongs depolarization and total action potential duration, increased QT interval
Lepromatous leprosy
Caused by Mycobacterium leprae (infects skin and superficial nerves- glove and stocking loss of sensation), cannot be grown in vitro
Lepromatous is diffusely over skin with LEONINE (lion like facies) COMMUNICABLE, HIGH BACTERIAL LOAD, LOW CELL MEDIATED IMMUNITY, no granulomas
Largely Th2 (humoral response)
Severe neuropathy
Degree of JVD correlates with
CENTRAL VENOUS PRESSURE
Helminth infection in US
Enterobius vermicularis
Alkaptonuria
Deficiency of homogentisate oxidase, the enzyme that converts homogentisate to MALEYLACETOACETATE
Dark urine dt oxidation of homogentisate
Homogentisate deposits in tissues lead to connective tissue discoloration and organ damage
Tx- low tyrosine and phenylalanine diet
Kussmaul sign
High JVP with inspiration
- ventricle cannot accept high venous return
Seen in:
Constrictive pericarditis
Restrictive cardiomyopathy
RV MI
NOT SEEN IN TAMPONADE
5 anti TNF a inhibitors
Infliximab Adalimumab Golimumab Certolizumab Etanercept (decoy receptor)
Neutralizing abs can form if patient on long term therapy and disease worsens
IL6
Pyrogen
Stimulated liver to synthesis acute reactive proteins
Secreted by macrophages
Idiopathic intracranial hypertension (pseudo tumor cerebral)
Presents in young obese F with daily HA (worsens with Valsalva), bilateral papilledema, transient visual disturbances
Increased intracranial pressure compresses the optic nerves, resulting in impaired axoplasmic flow and optic disc edema
Increased intracranial pressure transmitted through CSF in subarachnoid space, which is continuous with optic nerve sheath
Amyotrophic Lateral Sclerosis
LMN and UMN damage
50 year old M, slow progressive course, arm weakness, dysphasia to solids/liquids, some flaccid muscles, some spasticity, NO SENSORY SYMPTOMS
Familial cases- zinc copper superoxide dismitase deficiency
Succinylcholine MOA
Depolarizing neuromuscular agent used to induce skeletal muscle relaxation during surgery and intubation
Acts as a COMPETITIVE AGONIST of NICOTINIC ACETYLCHOLINE RECEPTORS of motor end plate, where it induces persistent depolarization —> desensitization and skeletal muscle paralysis
Succinylcholine is rapidly HYDROLYZED BY PLASMA PSEUDOCHOLINESTERASE- allows for 10% of drug administered to reach NMJ—> duration of <10 mins
Pts with pseudocholinesterase deficiency are unable to metabolize succinylcholine, so a large amount of drug reaches NMJ. Heterozygotes maybe have longer paralysis and homozygotes can have persistent paralysis for several hours
ABL proto oncogene
Non receptor tyrosine kinase
Chronic myelogenous leukemia
Mets to liver
Colon, stomach, pancreas
Osteocytes remain connected by
Gap junctions - exchange nutrients and waste products
Variant (Prinzmetal) angina dx
Intracoronary ergonovine
- acts on smooth muscle serotonergic (5HT2) receptors
- admin during angiography—> induces vasospasm
Intracoronary ACh
- acts on endothelial muscarinic receptors
- in healthy endothelium—> ACh triggers NO release and vasodilation
- in endothelial dysfunction—> ACh induces spasm
AVOID PROPRANOLOL DT UNOPPOSED ALPHA STIMULATION
Chronic pancreatitis
ETOH in adults
Cystic fibrosis in peds
Posterior horn
Sensory nerves up to cortex
Pain and temp
Early onset Alzheimer’s in Down syndrome
AMYLOID PRECURSOR PROTEIN (APP) located on chrom 21–> extra copy—> accelerates amyloid accumulation and leads to early onset AD
Alzheimer’s dx before age 65
Characteristic changes include
- INTRACELLULAR NEUROFIBRILLARY TANGLES (hyperphosphorylated tau)
- AMYLOID BETA PLAQUES (amyloid beta is abnormal fragment of AMYLOID PRECURSOR PROTEIN, normally involved in synaptic repair, in AD, protein not properly cleared—> harden into plaques and accumulate in brain/vessel tissue)
False positives on RPR
RPR- nonspecific screening test for syphilis that detects anticardiolopin abs
False positives- infectious mono, HAV, malaria, pregnancy, antiphospholipid syndrome (abs against cardiolipin)
HLADR4
DM1
RA
Addison disease
Which malaria species leave hypnozoites in liver?
P. Vivax and p. Ovale capable of causing relapses after recovery from primary infection.
Both organisms leave dormant hypnzoites in liver
Patients requiring stem cell transplant dt congenital genomic disease should use a
MATCHED UNRELATED DONOR
Donor cells will be HLA matched but will not have genomic mutation causing disease
Metoclopromide contraindications
Known seizure disorder
Parkinson’s
Bowel obstruction
MOA- D2 receptor antagonist—> increases resting tone, contractility, LES tone, MOTILITY (used for motility in gastroparesis)
Anti emetic, persistent GERD
AE- Parkinsonian effects, drug interaction with digoxin, TARDIVE DYSKINESIA (irreversible)
Neuroleptic malignant syndrome
AE of dopamine blocking receptors in the brain by antipsychotics
Diffuse muscle rigidity, high fever, autonomic instability (HTN, tachycardia), AMS
Elevated creatine kinase dt rhabdomyolysis which can result in acute renal failure
Tx: fluids, DANTROLENE- antagonizes ryanodine receptors and inhibits Ca release from sarcoplasmic reticulum
Can also use BROMOCRIPTINE (DA agonist)
T cell ALL
Less common
COMMON ADOLESCENT BOYS (teens to 20s)
- parents as mass (LAD, MEDIASTINAL MASS, anterior with pleural effusions)
Tumor compression may occur
- SVC syndrome
- tracheal obstruction
Pathology- blasts—> CD7+, CD2, 3, 4, 5, 8+
NOT CD10+
Antibody dependent cell mediated cytotoxicity
Type II HSR where IgG or IgM binds to antigens expressed on cell surface
Antibodies recognized by Fc receptors on immune cells, triggering release of perforins and granzymes that lead to cell lysis
Broca’s area and Wenicke’s area artery supply
Middle cerebral artery
Drugs that act on microtubules (Microtubules Get Constructed Very Poorly)
Mebendazole (antihelminthic) Griseofulvin (anti fungal) Colchine (anti gout) Vincristine/vinblastine (anti cancer) Paclitaxel (anti cancer)
Alemtuzumab
Mab targets CD52 positive cells
(T, B, NK, monocytes)
Used for refractory MS and CLL
Abdominal aortic aneurysm
Atherosclerosis
Smokies is major risk factor
Common causes of NORMAL ANION GAP METABOLIC ACIDOSIS
Diarrhea
RTA
- loss of bicarb from kidneys/GIT and serum Cl increased to maintain electro neutrality
EXCESS NORMAL SALINE INFUSION
- excess NaCl increases Cl and causes hyperchloremia, this causes bicarbonate to shift into cells to maintain electronegative balance
This “loss of bicarb” decreases pH
Infusion of increased volume increases intravascular volume—> kidneys respond by increasing Na excretion—> increased Na in urine
Para aortic LN drainage
Endometrial cancer
Ovarian cancer
Testicular cancer
Mets
Pulses paradoxus
Exaggerated drop (>10mmHg) in systolic blood pressure during inspiration
Detected by inflating BP cuff and gradually deflating it
The difference between systolic pressure at which Kortokoff sounds frost become audible during expiration and the pressure at which they are heard throughout all phases of respiration quantifies pulsus paradoxus
*inspiration causes increased systemic return, resulting in increased R heart volumes. Normally, this results in expansion of the RV into pericardial space with little effect on L heart. In conditions that impair expansion into the pericardial space (I.e tamponade), the increased RV volume occurring with inspiration leads to bowing of interventricular septum towards the LV. This leads to decrease in LV end diastolic volume and stroke volume with a resultant decrease in systolic pressure during inspiration
Ramelteon
Melatonin agonist
Binds with high affinity to melatonin receptors in suprachiasmatic nucleus
Lowest side effect burden in elderly
Partial hydatiform mole immunohistochemistry stain
p57 positive
69XXX, XXY- maternal and paternal DNA
Enlarged villi with focal trophoblastic proliferation
Fetal/embryonic tissue present
Ferritin
Iron stored intracellularly as ferritin
Stored in macrophages of liver and bone
Ribavirin
Inhibits IMP dehydrogenase
Blocks conversion of IMP to GMP
Inhibits synthesis of guanine nucleotides (purines) so less G for virus to use to replicate its genome
Atrophy of mammillary bodies
Wernicke encephalopathy (thiamine deficiency causing ataxia, opthalmoplegia, confusion)
Herpesvirus acquire their envelope from where?
Host cell NUCLEAR MEMBRANES
Constrictive population
Very low birth rates
Low mortality rates
Long life expectancy
Shrinking population
Very advanced countries
Flutamide
Competitive antagonist at androgen receptors
Non steroidal anti androgen
Used to treat prostate cancer
Decreased endogenous androgen activity —> inhibits tumor growth and may contribute to tumor regression
Tumor suppressors
Inactivation eliminates oversight of cell cycle
Loss of function mutation, both alleles must be mutated for loss of function
Radial nerve nerve roots
Posterior cord C5-T1
Proximal radial nerve injury can occur at nerves superficial location in axilla
- repetitive pressure/trauma of crutches
- sleeping with arm over chair (Saturday night palsy)
S/s: weakness/paralysis of forearm, hand, finger extensor muscles (wrist drop, absent tricep reflex) and sensory loss in posterior arm abs forearm, dorsolateral hand and thumb
IL4
IgE class switching
Induces Th2 differentiation
Scarlet fever
Rash after GAS pharyngitis
Skin rxn dt ERYTHROGENIC TOXIN- transferred by lysogenic bacteriophage
sandpaper skin, strawberry tongue, desquamates
GLUT3 and 1
Insulin INDEPENDENT
Neurons and placenta
Subarachnoid hemorrhage and prophylactic CCB
CCB- nimodipine
Delayed cerebral ischemia dt cerebral vasospasm presents 3-12 days after initial SAH- change in mental status, neuro deficits
Nimodipine, selective CCB improves outcomes in patients with cerebral vasospasm by inducing cerebral vasodilation and decreasing calcium dependent excitotoxicity.
Thoracic outlet syndrome
Pain and parathesia in distribution of the inferior roots of the brachial plexus (lower trunk C8 to T1)
IP3 pathway
GPCR—> activated phospholipase C—> phospholipase C hydrolyzes PIP2–> IP3 and DAG—> IP3 mobilizes calcium from ER and DAG directly activate protein kinase C
Truncus arteriosus
Ascending aorta and pulmonary trunk
Ligamentum teres
Remnant of umbilical vein
Letrozole
Ovulation induction agent
Inhibits aromatase (prevents androgen to estrogen conversion) and suppresses ovarian estradiol production
In response to LOW ESTROGEN—> pituitary releases more FSH and LH—> stimulates ovulation
LiFraumeni syndrome
AD mutation
Loss of heterozygosity in p53 tumor suppressor
- pts inherit one abnormal copy and develop cancer when second allele somatically mutated
Multiple malignancies at early age- sarcoma, BREAST, leukemia, adrenocortical carcinoma
Pilocytic astrocytoma
Low grade astrocytoma in peds and young adults
Usually in posterior fossa, in cerebellum hemispheres
Cystic lesion, presents with obstructive hydrocephalus dt external compression of 4th ventricle - ataxia, clumsiness, s/s high intracranial presssure (n/v, AMS)
ASSOC WITH NF1
“Cyst with mural nodule”
Histology- astrocyte origin, GFAP+, ROSENTHAL FIBERS- eosinophilic, corkscrew fibers with astrocytic processes
BENIGN, good prognosis
M3 second messenger
IP3
M3 stimulation—> INCREASE IP3
- bronchoconstriction
- increased insulin release and GI motility
- bladder contraction
- pupillary constriction
- peripheral vasodilation (via NO)
Lateral pterygoid muscles
Only muscles of mastication that OPEN THE JAW
Spasm of the lateral pyerygoids prevents spontaneous reduction of an anterior dislocation of the TMJ
Dopamine
Sympathomimetic
D1D2>B2>alpha
INCREASE BP (AT HIGH DOSES)
INCREASE HR
INCREASE CO
Used in unstable bradycardia, HF, shock
Inotropic and cheonotropic at lower doses dt B effects
Vasoconstriction at high doses dt alpha effects
Beta 1 receptor second messenger
cAMP
Beta 1 stimulation—> INCREASED cAMP
- INCREASED contractility and HR
- INCREASED renin release by JG cells of kidney
Sudan III stain
Identifies fat in stool
Identifies malabsorption of fat
Steroids and asthma
In addition to anti inflammatory effect—> steroids upregulate beta 2 receptors on bronchial smooth muscle to increase cellular responsiveness to adrenergic stimuli and potentiate the bronchodilator response to inhaled beta2 agonists
t(9;22)
Philadelphia chromosome, CML (BCR-ABL oncogene, tyrosine kinase activation)
Rare association with ALL
Encapsulated bacteria - Please SHiNE my SKiS
Pseudomonas aeroginosa
Streptococcus pneumoniae
Haemophilus influenzae type b
Neisseria meningiditis
E. coli
Salmonella
Klebsiella pneumoniae
group B Streptoccus
Capsules are antiphagocytic, opsonized and cleared by spleen
Capsular polysaccharide + protein conjugate serves as antigen in vaccines
Riedel thyroiditis
Thyroid replaced by fibrous tissue and inflammatory infiltrate
FIBROSIS MAY EXTEND TO LOCAL STRUCTURES (trachea, esophagus, mimics anaplastic carcinoma)
Considered manifestation of IgG4 related systemic dx (autoimmune pancreatits, retroperitoneal fibrosis, non infectious aortits)
FIXED HARD (rock like) PAINLESS GOITER
Campylobacter jejuni
Motile, curved, GN rod that is leading cause of gastroenteritis
Pathogen lives in gut of warm blooded animals and is transmitted via ingestion of contaminated food (poultry) and direct contact with domesticated animals
Manifestations include fever, cramping abd pain, watery diarrhea that may be bloody.
Assoc with Guillain Barre syndrome
Cladribine
Purine analog, mimics adenosine
Drug of choice for HAIRY CELL LEUKEMIA
Classic galactosemia
AUTOSOMAL RECESSIVE
Absence of galactose 1 phosphate uridyltransferase (GALT)—> prevents metabolism of galactose (derived from lactose)
Damage caused by accumulation of toxic substances (GALACTITOL) accumulates in LENS OF EYE (opacification)
Clinically- INFANTS with CATARACTS, LIVER DISEASE (hepatomegaly, jaundice), AMINOACIDURIA, MR, growth failure
Can predispose to E. coli sepsis in neonates
Treat- strict dietary lactose restriction
Aminoglycosides
Gentamicin Neomycin Amikacin Tobramycin Streptomycin
REQ O2 for uptake
Bind 30S ribosome, inhibit bacterial protein synthesis
NEPHROTOXIC, OTOTOXIC, NEUROMUSCULAR BLOCK
TERATOGENIC
IL1
Endogenous pyrogen—> acts on hypothalamus and increases set point of temperature in body
Increases synthesis of endothelial adhesion molecules—> allow neutrophils to enter inflamed tissue
Macrophage secreted
Rituximab
mab against CD20
- found in most B cell neoplasms
- non Hodgkin’s lymphoma, CLL, ITP, RA, TTP, AIHA
RISK OF OPPORTUNISTIC INFECTIONS:
- PML (JC virus)
- HEPATITS B REACTIVATION
TGFb and IL10
Attenuate immune response
OTC deficiency
Most common urea cycle disorder
Excess carbomoyl phosphate converted to orotic acid—> orotic acid accumulates and spills into urine
Vomiting, tachypnea, coma
HYPERAMMONEMIA AND ELEVATED OROTIC ACID IN URINE
Fenofibrate MOA
Lower TG levels by activating peroxisome proliferator activator receptor alpha (PPAR)—> decreased hepatic VLDL production and increased lipoprotein lipase activity
HLADR3
DM1 SLE Graves’ disease Hashimoto’s thyroiditis (also HLADR5) Addison disease
Lacunar infractions
Result of small vessel occlusion from lipohyalinosis and microatheroma formation in the penetrating vessels (LENTICULOSTRIATE ARTERIES)supplying the deep brain
Uncontrolled HTN and DM are major risk factors
Cavitary infarcts located in basal ganglia, posterior limb of internal capsule, pons, cerebellum
Complete hydatidiform mole
Non viable pregnancy contains two sets of paternal DNA, no maternal DNA
No fetal parts, snowstorm appearance on u/s
46XX or 46XY
Causes grape like masses of dilated abnormal chorionic villi with secretion of very high hCG and uterine enlargement
Rapid trophoblastic proliferation herighyens potential for malignant transformation to choriocarcinoma
S/s: vaginal bleeding and hyperemesis gravidarum
Nucleus solitarius
Medulla structure
Responds to changes in BP
Both aortic arch and carotid sinus send afferents to nucleus solitarius
Class IB antiarryhtmics
Lidocaine
Mexiletine
Block voltage gated sodium channels. Have weakest binding compared to other class I anti arrhythmics
Rapidly dissociate from Na receptor, little use dependence
Selective for ischemic myocardium and are used for ISCHEMIA INDUCED VENTRICULAR ARRHYTHMIAS
Burkitts lymphoma
B cell malignancy
CD19, CD20
Very aggressive
Key distinctions:
- Starry sky morphology
- EBV
- C myc translocation (t(8;14))
Endemic form- children, Africa/New Guinea, MANDIBLE mass, assoc with EBV, EBV infects B cells with CD21
Sporadic form- occurs in children, ABDOMINAL MASS (ileocecum or peritoneum)
Mixed UMN and LMN disease
Amyotrophic lateral sclerosis
Severing glossopharyngeal nerve effect on BP and HR
Severing the glossopharyngeal nerve sends the medulla a false signal that there is a sudden decrease in BP—> elicits baroreflex that results in increase in sympathetic outflow, leading to HTN and tachycardia
Clomiphene MOA
Clomiphene (inhibits hypothalamic estrogen receptors → disruption of normal negative feedback effect of estrogen → ↑ pulsatile secretion of GnRH → ↑ FSH and LH → stimulation of ovulation
Diphtheria toxin
AB toxin that ribosylates and inactivates elongation factor 2
This inhibits protein synthesis and leads to cell death
Cause of infertility in CF
Absent vas deferns (Azoospermia)
Increased fluid secretion exotoxins
ETEC:
- heat labile toxin- overactivates AC—> cAMP
- Heat stabile toxin —> overactivates GC—> cGMP, less NaCl reabsorption in gut
B anthracis - anthrax toxin, mimics AC, likely responsible for edematous boarders of cutaneous anthrax
V cholera- cholera toxin, overactivates AC by increasing cAMP by permanently activating Gs—> high Cl secretion into gut and water efflux
- VOLUMINOUS RICE WATER DIARRHEA
- death: profound dehydration, electrolyte losses, shock
Major basic protein
Located in eosinophils
CRYSTALLINE, ROD SHAPED on EM
Functions in destruction of parasites and contributes to epithelial damage in asthma.
Succinyl coA to succinate releases
GTP
Histoplasma capsulatum diagnosis
Urine antigen test
Mississippi and Ohio river valley
Bat/bird droppings, CAVES
Enlarged liver spleen, mouth ulcers, pancytopenia, hilar LAD, slow onset PNA
MACROPHAGES FILLED WITH YEAST CELLS
CELL MEDIATED IMMUNITY
Amphotericin B for systemic infection, fluconazole/itraconazole for local infection
Lowenstein Jensen agar
M. Tb growth
Need to treat pt before culture comes back Bc grows slow
Always stain with Ziehl Neelsen or Auramine rhodamine
Eatons agar
Cuktures Mycoplasma pneumoniae - requires CHOLESTEROL to grow
Culturing rarely used- usually diagnose via serology (abs), PCR (bacterial DNA), cold agglutinins
Colchicine MOA
Inhibits microtuble formation, which prevents leukocyte migration and phagocytosis, leading to a reduction in inflammation
AE- severe diarrhea, abdominal cramping, leukopenia, myelosuppression, hepatotoxic
GAS erythrogenic toxin transferred by
Lysogenic bacteriophage
Thyroid hormone resistance
Decreased sensitivity of hypothalamic- pituitary- peripheral tissue axis to thyroid hormones dt defect in thyroid hormone receptor (thyroid hormone receptor beta)
Levels of T4, T3, TSH INCREASED
Pts typically have goiter and develop ADHD
Neutrophil rolling
Selectin ligand on neutrophils (Sialyl Lewis X) binds to Selectins on endothelial cells—> neutrophils slow down and roll
Winters formula
1.5xbicarb + 8 +/- 2
Cluster A (odd/eccentric) 3
- Paranoid: suspicious, distrustful, hypervigilant
- Schizoid: prefers to be a loner, detached, unemotional
- Schizotypal: unusual thoughts, perceptions, behaviors
Th17 cells
Subset of CD4
Produce IL17
Important for mucosal immunity in GIT
Loss of Th17 cells shows GI bacteria in blood stream
Recruit neutrophils and macrophages
Dermatitis herpetiformis
Deposition of IgA immune complexes within DERMAL PAPILLA
Prurutic papulovesicles on extensor extremities, scalp, back, buttocks
Uterine leiomyoma
Fibroid
Irregular uterine enlargement
Can cause pelvic pressure, especially on bladder and colon—> leading to constipation
Struvite stones
Composed of magnesium ammonium phosphate
Occur after infection by urease producing bacteria (Proteus, Klebsiella)
Urine becomes alkaline, resulting in precipitation of magnesium ammonium phosphate salts—> may form large stones (staghorn calculi)
MC IN WOMEN AND PTS WITH INDWELLING CATHETERS (paraplegia)
RV characteristics
Low muscle mass Low resting oxygen extraction Coronary perfusion in BOTH SYSTOLE AND DIASTOLE More developed collateral circulation High ischemic preconditioning
Medullary thyroid carcinoma
From parafollicular cells (C cells)- produces calcitonin
Sheets of polygonal cells in amyloid stroma
Stains with CONGO RED
Associated with MEN2A and 2B RET mutations
Atomoxetine
Non stimulant treatment for ADHD
- less insomnia, loss of appetite
Selective norepi reuptake inhibitor
NO DIRECT EFFECTS ON DOPAMINE SYSTEMS IN BRAIN
- dopamine effects may cause euphoria (abuse potential)
Spinothalamic tract
Ascending
Pain and temp
OTC deficiency
Most common urea cycle disorder
Excess carbomoyl phosphate converted to orotic acid—> orotic acid accumulates and spills into urine
Vomiting, tachypnea, coma
HYPERAMMONEMIA AND ELEVATED OROTIC ACID IN URINE
Anorexia
BMI <18.5
Intense fear of weight gain
Distorted views of body weight and shape
Target cells
RBC with dark center, surrounding halo of pallor and dark peripheral ring
Form dt excessive surface area to volume ratio
Occurs in
Thalassemia, iron deficiency or structural mutations to Hb
Excessive membrane dt greater cholesterol to phospholipid ratios (liver disease, splenectomy)
- splenectomy pts usually devo target cells because spleen is primary organ that prunes excessive red cell membranes
What cells form fibrous cap on atheroma
VSMCs
- atherosclerosis initiated by endothelial injury—> increased expression of VCAMs—> migration and adherence of monocytes and T lymphs into intima—> infiltrating WBCs release cytokines and growth factors (PDGF, FGF, IL1)—> PROMOTES MIGRATION AND PROLIFERATION OF VASCULAR SMOOTH MUSCLE CELLS (VSMCs) in intima
VSMCs stimulated to synthesize extracellular matrix (collagen, elastin, proteoglycan) that form fibrous cap of atheroma
Food poisoning (exotoxins mediated)
S aureus, B cereus
Anticholinergic toxicity
Competitively inhibit ACh at muscarinic receptor. Need to increase ACh in synaptic cleft
Hot as a hare- high body temp, decreased sweat, decreased heat dissipation
Dry as a bone- decreased secretions
Red as a beet- flushed skin
Blind as a bat- paralysis of ciliary muscles and iris sphincter
Mad as a hatter- AMS, permeates BBB and affects CNS pathways
Full as a flask- decreased smooth muscle contractions
Fast as a fiddle- tachycardia, decreased vagal tone to SA node
Treat with PHYSOSTIGMINE (cholinesterase inhibitor, increase ACh levels by preventing degradation by cholinesterase)
Hand foot mouth disease
Oral ulcerations and vesicular extremity rash and herpangina (oral ulcers, high fever)
Caused by ENTEROVIRUS- coxsackie A
Complications include myocarditis, CNS disease
Infants, children
Summer season
Fecal oral
Caspofungin MOA
Blocks GLUCAN synthesis
Suppresses fungal wall synthesis
Candida, Aspergillus
Ceftaroline
5th gen cephalosporin
Binds PBP2a—> MRSA SPECIFIC
Covers MRSA and VRSA, NOT PSEUDOMONAS
b1 receptors where
Heart, kidneys
Increase HR, stimulate renin release
b1 block- low CO, low ECV—> low BP
Sideroblastic anemia
Genetic (X linked defect in ALA synthase gene), acquired (myelodysplastic syndrome), and reversible (alcohol, lead poisoning, B6 deficiency, copper deficiency, INH, linezolid)
Iron laden macrophages, RINGED SIDEROBLASTS in marrow—> Prussian blue stained mitochondria
Tx B6
Prevention of HSV2 recurrence
Continuous daily valacyclovir, acyclovir, famciclovir
Cimetidine
Histamine blocker
POTENT 450 INHIBITOR
ANTI ANDROGEN - gynecomastia, impotence, prolactin release
Crosses BBB and placenta
REDUCES CREATININE EXCRETION
Loeffler media/Tellurite plate
Loefflers- selective for C. diptheria
Terllurite- C diptheria produces gray black colored colonies
Competitive inhibitor
Increases Km
Vmax UNCHANGED
Leptin
Produced by adipocytes on response to short term food intake and long term adequacy of fat stores
Acts on hypothalamus to decrease appetite (obesity blunts this action)
During fasting states, leptin levels fall
Left horn of sinus venosus
Coronary sinus
Pulmonary HTN
Idiopathic Heritable Left heart disease (HF) Lung disease (COPD) Hypoxemic vasoconstriction (ie OSA) Thromboembolic (ie PE)
Renal adaptations during pregnancy
Volume expansion
Widespread vasodilation
Greater basement membrane permeability and decreased tubular reabsorption of filtered protein (trace protein normal in urine)
Increased cardiac output Increased RPF
Increased GFR
—> leads to increased creatinine clearance
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
Conditions pulsus paradoxus (drop in SBP of >10 mmHg) can occur
Severe asthma
COPD
Constrictive pericarditis
Tamponade
Ehrlichiosis
Ehrlichia chaffeensis is harbored by white tailed deer in SW, SE, mid Atlantic US
Transmitted by tick bite and spreads to tissues rich in MONONUCLEAR CELLS (bone marrow, LN, liver, spleen)
Leads to nonspecific symptoms (fever, chills, myalgia, HA), maculapapular rash and lymphopenia, thrombocytopenia, elevated aminotransferases
REPLICATES in membrane bound vacuoles in cytoplasm and appears as MULBERRY SHAPED INTRALEUKOCYTIC INCLUSIONS (morulae)
Treat with doxycycline
(MEGA= mulberry shaped in monocytes in Ehrlichia, granulocytes in anaplasma)
Anterolateral papillary muscle blood supply (2)
LAD and LCX
NADPH
Product of PPP
Needed for cholesterol and fatty acid synthesis and glutathione antioxidant mechanism
Tabes dorsalis
Caused by tertiary syphilis
Results from degen/demyelination of DCML and loss of dorsal roots
Patient with other STDs, difficulty walking, 5/5 strength in legs and arms, POSITIVE ROMBERG (loss of proprioception), wide based gait, fleeting, recurrent shooting pains, loss of ankle/knee reflexes, ARGYLL ROBINSON PUPILS
CYP450 Inhibitors
TMP SMX, Metronidazole, macrolides Azole antifungals Amiodarone Cimetidine Grapefruit juice
INCREASE WARFARIN EFFECT, INCREASE BLEEDING RISK
Cranial nerve III (oculomotor nerve palsy)
Double vision, eye lid droop, LATERAL AND INFERIOR eye deviation at rest, dilated pupil that does not react to light
Caused by posterior communicating artery aneurysm (compresses CNIII)—> causes injury to outer parasympathetic layer of CNIII (pupillary response) and injury to deeper somatic fibers (extraocular muscles)—> pupil not reactive to light, dilated AND ptosis and down and out gaze
Acetazolamide MOA
Carbonic anhydrase inhibitor that inhibits HCO3- reabsorption and H+ secretion in PCT
Secreted H+ is normally buffeted by NH3 and excreted as NH4+, so by reducing H+ secretion, acetazolamide also reduces NH4+ excretion
Can cause metabolic acidosis with decreased plasma bicarb and low pH
Used for acute angle closure glaucoma
Oxygen transfer across alveolar membrane depends on 1. Gas diffusion rate and 2. Capillary blood perfusion rate
In healthy lungs- diffusion of oxygen occurs rapidly- RBCs become fully saturated with o2 at 1/3 of total capillary length.
For this reason, o2 saturation does not fall even with large CO (exercise). Normal o2 transfer is perfusion limited (diffusion so fast that O2 transfer depends on perfusion rate (CO) only.
Flip for interstitial lung disease
Diffusion limitation is a mechanism of hypoxia that occurs in diseases that disrupt the alveolar- capillary membrane (emphysema, pulmonary fibrosis). Fibrotic thickening of interstitial space (between air and blood) increases distance O2 must cross, limiting o2 diffusion
During exercise- increase in pulmonary blood flow accelerates transit time thru pulmonary capillaries, reducing the time for oxygen extraction.
In patients with diffusion limitation, increased blood flow during exercise can result in exertional hypoxemia, even if oxygenation normal at rest
Locus ceruleus
Paired PIGMENTED brainstem nucleus in POSTERIOR ROSTRAL PONS NEAR FLOOR OF 4th VENTRICLE
Principle site of NOREPINEPHRINE synthesis
Pts with b/l pontine hemorrhage typically present with coma dt disruption of RETICULAR ACTIVATING SYSTEM
- total paralysis with extensor posturing dt corticospinal and corticobulbar tract injury and pinpoint pupils dt descending sympathetic tract damage
2,3 BPG
Binds Hb and lowers it’s O2 affinity, thereby enhancing the release of bound O2
2,3 BPG is generated via glycolytic substrate 1,3 BPG—> accumulates in pyruvate kinase deficiency
Hepatitis A
RNA picornavirus
Fecal oral route dt CONTAMINATED WATER OR FOOD WITH RAW OR STEAMED SHELLFISH
Self limited disease
5 orgs causing infections in CGD
S aureus Pseudomonas Serratia Nocardia Aspergillus
Maculopapular rash after amino penicillin associated with
EBV PHARYNGITIS
Ornithine transcarbamylase deficiency
High ammonia, hyperammonemia
Increased blood glutamate
BUN decreased
OROTIC ACID IN URINE
NO CITRULLINE
X LINKED RECESSIVE
Cerebral edema, coma, lethargy, convulsions, death
Congenital CMV infection
Triad of:
- Cutaneous hemorrhages (blueberry muffin)
- Sensorineural deafness
- Periventricular calcifications
In adults- CMV infection causes influenza like syndrome with mild fever and LAD (referred to as heterophile negative mononucleosis)
Cauda equina syndrome
Progressive low back pain
B/l LE weakness
Bowel/bladder dysfunction
Impaired perineal sensation
Dt disruption of nerve roots to the sciatic nerve (LE weakness, radical at low back pain), pudendal nerve (saddle anesthesia), and pelvic splanchnics
Pelvic splanchnics S2-S4 provide parasympathetic innervation to hindgut, bladder, urinary sphincters that promote peristalsis, bladder emptying, pelvic floor relaxation to defecate—> CONSTIPATION, DIFF URINATING prominent symptoms of cauda equina dt loss of PNS input to bladder and bowel
M2 second messenger
cAMP
M2 stimulation—> DECREASE cAMP
- DECREASED cardiac contractility and HR
Typhoidal Salmonella (S typhi, S paratyphi)
Humans only
Water/food contamination
Developing countries
Invades enterocytes—> blunted neutrophil response dt CAPSULAR ANTIGEN Vi—> extensive intracellular replication in macrophages—> spreads thru lymphatics and RES
Causes TYPHOID FEVER- progressive fever (pulse temperature dissociation)
- ROSE SPOTS, abd pain
- hepatosplenomegaly, GIB, perforation
Crushing syndrome
Iatrogenic (exogenous corticosteroids)
Adrenocortical adenoma (secretes excess cortisol)
ACTH secreting pituitary adenoma (Cushing disease)
Paraneoplastic syndrome (ACTH secretion by tumors)
Dextrans
Viridans streptococci produce dextrans that aid in colonizing history surfaces (dental cavities, heart valves)
Viridans strept cause subacute endocarditis in pts with preexisting cardiac valvular effects after dental manipulation
Pompe disease
Lysosomal a1,4 glycosidase deficiency
Inability to degrade lysosomal glycogen
Cardiomegaly, muscle weakness, death by 2
Glycogen like material in inclusion bodies
Amino acid precursor of serotonin
Tryptophan
MC cause subarachnoid hemorrhage?
Rupture of saccular (berry) aneurysm
Berry aneurysms occur in autosomal dominant poly cystic disease
Skin puckering/retraction seen in invasive breast carcinoma caused by malignant infiltration of
Suspensory ligaments of the breast
- malignant infiltration of these ligaments causes fibrosis and shortening—> traction on skin with distortion of breast contour
Histolopathology of Alzheimer’s
Neurofibrillary tangles of hyperphosphorylated tau protein
Extracellular senile plaques consisting of ABeta amyloid
Granulovacuolar degeneration and Hirano bodies
Androgenetic alopecia
MC type of hair loss in men and women
Hair loss driven by genetics and hormones (circulating androgens)
Occurs at temporal areas and vertex, progresses throughout life
Polygenic inheritance with variable expressivity —> severity of hair loss depends on hormonal and genetic factors and vary between males and females
Chemoreceptor trigger zone location
Floor of fourth ventricle houses area postrema—> contains CTZ
Vomiting reflex can be triggered by vagal stimulation caused by intense visceral pain
Metoclopromide is dopamine antagonist that acts at area postrema to prevent n/v
EBV associated diseases (5)
- Mono—> positive heterophile antibodies
- Lymphomas (endemic Burkitt)
- Nasopharyngeal carcinoma (Asians)
- Lymphoproliferative dx in transplant pts
- Aplastic anemia—> rare, HYPOCELLULAR MARROW WITH DIFFUSE FATTY INFILTRATE
EBV INFECTS B CELLS VIA CD21
What is required for B cell class switching
Signal 1. Th cell activation via PEPTIDE or we ration by APC
- need CD3 on T cell
Signal 2. Co stimulation on T cell via B7 on APC and CD28 naive T cell
NEED CD40 receptor on B cell and CD40L on Th cell for class switching
Th cells secrete cytokines that determine Ig switching of B cells
In vaccines that DO NOT have peptide antigen, WEAKER immune response, NO ab class switching—> will only make IgM abs
Competitive inhibitor
Increases Km
Vmax UNCHANGED
Azole MOA
Inhibit ergosterol (cell membrane) synthesis
Bordet Gengou agar
Bordatella pertussis
Prepared from
Potatoes
Granulomatous infections (8)
Tb Leprosy Fungal PNA (histo, blasto, coccidio) Bartonella (cat scratch dx) Brucellosis Listeria in infants (granulomatosis infanseptica) Schistosomiasis (worm) Syphilis (gummas)
Cocaine intoxication
Psychotic symptoms (paranoid delusions)
Euphoria
Agitation
S/s: sympathetic stimulation (tachycardia, diaphoresis, mydriasis)
LH in females
Ovulation
High estrogen from ovaries (stimulated by FSH) have positive feedback on LH and cause LH surge—> rupture of dominant follicle and ovulation
Menotropin (human menopausal gonadotropin) mimics FSH and triggers development of dominant ovarian follicle —> exogenous bhCG administered (similar structure to LH, therefore mimics LH surge and induces ovulation. Exogenous bHCG mimics LH surge
Cyclosporine and tacrolimus induced HTN treatment
DILTIAZEM- impairs metabolism of cyclosporine/ tacro and treats HTN so can use lower dose of cyclosporine
Myasthenia gravis
Autoimmune dx caused by auto antibodies directed against NICOTINIC ACETYLCHOLINE RECEPTORS on POST SYNAPTIC MEMBRANE of NMJ
Antibody binding leads to receptor degradation and complement mediated damage of postsynaptic membrane, prevent action potentials to be triggered
Pts commonly have FLUCTUATING WEAKNESS that worsens throughout the day and most often includes EXTRAOCULAR (ptosis, diplopia) and bulbar (dysphagia, fatiguable chewing) muscles
Most patients have thymus abnormalities (thymoma, thymus hyperplasia) that appear as ANTERIOR MEDIASTINAL MASS
Aortic aneurysm, ascending or arch
Tertiary syphilis (syphilitic aortitis) Vasa vasorum destruction
Antibody function (3)
- Opsonization
- Neutralization
- Complement fixation
Main respiratory drive in COPD
Hypoxemia
- COPD pts have blunted response to PaCO2 dt chronic CO2 retaining.
Peripheral chemoreceptors primarily sense arterial pressure of oxygen and can be suppressed (decreased respirations) with supplemental oxygen
Epidural hematoma
Rupture middle meningeal artery
Lentiform shaped
Heat related illness in elderly dt
Tonic contraction of peripheral vasculature - limits heat transfer to skin
Reduced sweat gland density- limits ability to dissipate heat via evaporation
Reduced effective epidermal area available for heat transfer- loss of rete pegs and dermal capillaries
Fourth pharyngeal pouch gives rise to
Superior parathyroid
Ghrelin
Produced primarily in stomach in gastric pits in response to fasting
- levels surge leading up to meals and fall after eating
- stimulates appetite and promotes weight gain
- caloric restrictions and falling fat stores lead to increased ghrelin (along with decreased leptin and insulin levels) which limits weight loss from dietary restriction alone
Bariatric surgeries can lose significant number of ghrelin secreting cells—> lower ghrelin, less appetite stimulation in response to fasting, promoting weight loss
Malignant PKU
Tetrahydrobiopterin (BH4) deficiency caused by dihydropterin reductase
BH4 is cofactor for conversion of Phe to Tyr and Tyr to DOPA
DOPA is precursor of melanin and catecholamines—> deficiency of BH4–> low dopamine—> hyperprolactinemia
MUST SUPPLEMENT BH4 and Tyr in malignant PKU
Presentation is classic PKU patient that does not improve with Phe restricted diet
Paratracheal, mediastinal, hilar LN drainage
Lung cancer Esophageal cancer Hodgkin lymphoma Mets Granulomatous pulmonary diseases
Tetracycline risk in pregnancy
Teeth discoloration
Mesonephros is MALES
Wolffian duct and forms ductus deferents and epididymis
Aortic arch baroreceptors innervated by
Vagus
Methionine is precursor/intermediate of (4)
- Cysteine
- Carnitine
- Taurine
- Lecithin
Muromonab
Monoclonal ab used to prevent organ transplant rejection
Binds CD3 receptors on T cells—> triggers apoptosis, reduced T cells and IL2 activity
Hormone sensitive lipase
Enzyme in adipose tissue that catalyze the mobilization of stored triglycerides into FREE FATTY ACIDS and GLYCEROL
HSL activated in response to stress hormones:
Catecholamines, glucagon, ACTH and is inhibited by insulin
- stress hormones activate Gs on adipocytes
—> leads to increased cAMP production a d activation of protein kinase A. PKA phosphorylates and activates HSL, stimulating lipolysis
FFA and glycerol taken up by liver for gluconeogenesis
Liver oxidizes FFAs to acetyl coA—> metabolized to ketones (acetoacetate, beta hydroxybuterate) or shunted into TCA cycle
In BRAIN- FFAs do not cross BBB, so only ketone bodies/glucose can be used and RBCs can only use glucose (no mitochondria)
Additive
Effect of substance A and B together is equal to the sun of their individual effects
Aspirin and acetaminophen
Sodium dependent glucose transporters are found where
GIT and kidneys
In both locations- glucose transported against its concentration
Coupled with abs going down it’s concentration gradient
IL12 receptor deficiency
IL12 triggers differentiation of T cells to Th1
Activates Th1 produce IFN gamma
Important for response to intracellular infections
Children born with deficient receptors have weak Th1 response and low levels of IFN gamma
Increased susceptibility to
- Disseminated salmonella
- Disseminated nontuberculous mycobacterial
- Disseminated BCG after vaccine
Treatment- IFN gamma
Bacillary dysentery
Shigellosis
Acute infection of bowel caused by Shigella species
Bloody diarrhea, fever, vomiting, abd pain
Spread FECAL ORAL
DAY CARE SETTING
LOW INFECTIOUS DOSE
Familial hypercholesterolemia
AD
Defects in gene encoding LDL RECEPTOR
FH inherited with gene domain effect in which homozygotes are more adversely affected that heterozygotes
Offspring of a homozygote and genetically normal individual will be affected heterozygotes-> elevated plasma LDL cholesterol levels
Pemphigus vulgaris
Hallmark: ACANTHOLYSIS- loss of connections between keratinocytes
Autoantibodies (IgG) against DESMOGLEIN 1 and 3
- component of desmosomes
- TYPE II HSR
- reticular pattern on IF
Disrupts connections in stratum spinosum
+ Nikolsky sign
Occurs adults 30-60
LARGE FLACCID BULLAE (loose and floppy)
Often presents with ORAL BULLAE AND ULCERATIONS
Theophylline
2 or 3 line for asthma treatment
Inhibits phosphodiesterase—> increases cAMP in airway smooth muscle and leads to bronchodilation
Also antagonizes adenosine receptors to prevent bronchoconstriction
Narrow therapeutic window—> toxicity results in TACHYCARDIA, PALPITATIONS, SEIZURES, TREMORS, AGITATION
Aztreonam
Monobactam (beta lactamases ring sits alone)
Binds PENICILLIN BINDING PROTEIN3 (PBP3)- only in GN
ONLY ACTIVE AGAINST GN, active against pseudomonas
NO CROSS REACTIVITY WITH PCN- can give to PCN allergic pts
SYNERGISITC WITH AMINOGLYCOSIDES
Myopia (near sightedness)
Refractive error caused by INCREASED ANTERIOR POSTERIOR DIAMETER of eye
Image falls anterior to the retina—> pts have problems seeing objects at a distance
Dermatitis herpetiformis
Associated with CELIAC DISEASE
Extensor surfaces, itchy
IgA deposition in dermal papillae
- abs triggered by gluten cross react with skin
Bx- microabscesses with neutrophils, on IF: IgA deposition at tips of dermal papillae
Transferrin
Transports iron in blood
INCREASES when iron stores are low
Lab value- Total Iron Binding Capacity
Transposition of great vessels
Right to left shunt cyanotic congenital heart disease
Central cyanosis- normal CO, not enough O2
- blue lips, nails, warm extremities
FAILURE OF AORTICOPULMONARY SEPTUM TO SPIRAL
- ANTERIORLY positioned aorta connected to RV and posteriorly positioned pulmonary artery connected to LV
- pulmonary and systemic circulations separate absexist
Aminoglycosides (gentamicin) risk in pregnancy
Sensorineural hearing loss
Damages CNVIII
Spore components
Keratin like coat- impermeable
Cortex/core wall- peptidoglycan, innermost layer, mainly structural
Dipicolonic acid- heat resistance
Bacillus and clostridium species
Circulation changes at birth
Pulmonary vasodilation and REDUCED pulmonary vascular resistance
Increases SVR dt umbilical cord clamping
—> decreased pulmonary pressure and increased SVR reverse right to left blood flow across PDA to LEFT TO RIGHT SHUNTING
PDA closes 24-48 hours after birth
Squamous cell carcinoma
2nd MC skin cancer
Arises from squamous cells in epidermis
Occurs in sun exposed areas, actinic keratosis is a precursor to SCC
- face, lips, ears, hands
- DNA damage by UV light
Occurs in older pts (>75yo), rarely metastasize
RED SCALING PLAQUES WITH SHARP BORDERS, ULCERATE, CRUST/ BLEED
Bx: KERATIN PEARLS
Risk factors:
- sun exposure
- IMMUNOSUPPRESSION (organ tx, HIV, steroids)
- chronic skin inflammation (chronic ulcers, burns)
- ARSENIC EXPOSURE (contaminated drinking water)
Immune privilege
Eyes, testes
Certain anatomic sites have inherent immune privilege, in which inflammation is inhibited by multiple mechanisms (physical barriers, lack of lymphatic, low expression of MHC I); this helps limit potential organ damage from a robust inflammatory response
Self antigens located in immune privileged sites can be recognized by T cells that escape negative selection in thymus.
If self antigens released into lymphatic as a result of trauma, T cells may recognize self antigens as foreign and mount a response in both injured organ and non injured organ. Bacterial introduction and exposure during trauma may upregulate inflammation, increasing chances that auto reactive T cells will develop
** trauma to the eye, an organ that has inherent immune privilege, can lead to release of previously sequestered antigens that T cells recognize as foreign—> can lead to subsequent inflammation and blindness in both injured and uninjured eye
Thalidomide risk in pregnancy
Limb malformation
Delusional disorder
More than 1 delusion for more than 1 month in absence of other psychiatric symptoms
Behavior is not obviously bizarre and functioning is not significantly impaired
Necrotizing fasciitis
Infection of deep tissues dt GAS PYROGENIC EXOTOXIN RELEASE
Requires emergent surgical debridement
Type 2: GAS, sometimes by staph, occurs in HEALTHY PEOPLE AFTER MONOR SKIN TRAUMA
Classic case: minor trauma, redness/warmth, PAIN OUT OF PROPORTION TO EXAM, fever, hypotension
Giemsa stain (6)
Stains nucleic acids
Rickettsia Chlamydia Trypanosomes- causes Chagas dx Plasmodium Borrelia H pylori
Neurophysins
Carrier proteins for OXYTOCIN and ADH
Oxytocin and ADH are carried by neurophysins from their site of production in cell bodies of paraventricular and supraoptic nuclei to their site of release in the axon terminals of posterior pituitary
POINT MUTATIONS in neurophysin II cause HEREDITARY HYPOTHALAMIC DIABETES INSIPIDUS—> disorder resulting from insufficient ADH release into circulation
Listeria monocytogenes
Facultative intracellular GP rod that causes febrile gastroenteritis
Evades host immunity by:
- LISTERIOLYSIN O (generates pores in phagosome membranes, allows phagocytosed Listeria to escape into cytoplasm of monocytes and avoid lysosomal destruction
- actin based trans cellular spread (hijacks actin based motility mechanism of host cells, which allows it to spread cell to cell without re entering extracellular space. Reduces exposure to abs and phagocytic cells
Infections controlled primarily by cytotoxic t cells
Pregnant women in 3 trimester are at greatest risk
Lipooligosaccharide
- endotoxin
- similar to LPS
- found on non enteric GNs
- N meningidits more important example
von Willebrand disease
AD bleeding disorder caused by either a deficiency or qualitative defect in vWF (multimeric protein that is required for platelet adhesion by binding platelet Gp1b)
vEF normally produced by endothelial cells and megakaryocytes
Abnormal vWF causes defect in INITIAL adhesion of normal platelets to damaged vessel
vWF also carries factor VIII, so those levels will also be low—> prolonged PTT
Spontaneous bleeding, prolonged bleeding time, menorrhagia
Normal platelet count
Prolonged bleeding time (indicates platelet pathology)
Prolonged PTT (intrinsic pathway defect)
ABNORMAL PLATELET AGGREGATION ON RISTOCETIN dt abnl vWF
Tx- desmopressin, which releases vWF from Weibel Palade bodies of endothelial cells
Incomplete obliteration of processus vaginalis causes: (2)
- Communicating hydrocele
- INDIRECT inguinal hernia - common in children, pass thru deep inguinal ring and covered by internal spermatic fascia, lateral to inferior epigastric vessels
- persistent communication between scrotum and abdominal cavity
- both present as asymptotic scrotal mass that increases in size with Valsalva
Entamoeba histolytica
Amoeba that causes colitis (bloody, mucusy diarrhea) and liver abscesses characterized by ulcers with undermining edges (flask shaped) that contain cysts and trophozoites
Anchovy paste exudate in liver abscess
Trophozoites can invade colonic wall abs disseminate through blood
Transmitted fecal- oral, ingesting contaminated water, developing nations (travel/residence)
Lateral horn
In thoracic section of spinal cord
Autonomic nerves
SA/AV node blood supply
RCA
- infarct may cause nodal dysfunction (bradycardia, heart block)
Multiple myeloma
Plasma cell malignancy—> excess production of immunoglobulins
DEPENDENT ON IL6
Disorder of older patients
SPEP: M spike
CRAB:
hyperCalcemia- osteoclast mediated bone resorption, caused by cytokines from myeloma cells, “PUNCHED OUT lesions” on XR, esp vertebral column, elevated CALCIUM
Renal failure- light chains and hypercalcemia, excess light chains cannot be reabsorbed and reach distal tubule—> form obstructing casts—> light chains in urine= BENCE JONES PROTEINS
Anemia
Back pain and bacterial infections- decreased production of normal igs, depressed humoral immunity—> s PNA, S aureus, E. coli
ROULEAUX FORMATION
Paget disease of bone
HIGH serum alkaline phosphatase, normal calcium and phosphate
Caused by abnormal osteoclasts that accelerate bone remodeling, resulting in bone pain, bitemporal skull enlargement, hearing loss, abnormal bone architecture with increased bone density, cortical thickening, and bowing
Feared outcome: osteosarcoma
CHOLANGIOCARCINOMA
Cancer of bile duct epithelial cells
Symptoms from bile obstruction
Key risk factors:
- CHRONIC BILIARY INFLAMMATION
- primary sclerosing cholangitis (UC)
- CLONORCHIS SINESIS
Rifampin MOA
Inhibits bacterial RNA polymerase
Leukocidin
Protease that kills leukocytes and causes necrosis
Expressed by certain staph aureus strains
Causes necrotizing PNA, skin/soft tissue abscesses
Acute pancreatitis
Gallstones, ETOH
Work of the heart—> myocardial O2 demand
Preload (LVEDV/P)
After load (MAP)
Contractility (ejection fraction)
HR
Hearts starved for O2–> reduce O2 demand
Low output—> need to increase work
Alkaptonuria
AR disorder of tyrosine metabolism
Deficiency of homogentisic acid dioxygenase blocks homogentisic acid metabolism, preventing conversion of tyrosine to fumarate
Homogentisic acid accumulates in body and is excreted in urine—> turns black
Deposits in cartilage, connective tissue—> ochronotic arthropathy and ochronosis
Primary hyperaldosteronism (Conn syndrome)
High aldosterone, low renin
Treatment resistant HTN
HTN
Hypokalemia
Metabolic alkalosis
Does not directly cause edema dt aldosterone escape mechanism
Methemoglobinemia
Caused by oxidation of ferrous ions (Fe2+) in heme to ferric (Fe3+) which is unable to bind oxygen
Nitrites can induce it—> results in tissue hypoxia
Treat with METHYLENE BLUE
- converts Fe3+ to Fe2+—> restores blood O2 carrying capacity and tissue O2 availability
Decreased cAMP receptors
Alpha 2 (CNS sympatholytic, decreased insulin release)
Muscarinic 2 (lower cardiac contractility and HR)
Primary osteoporosis
Decreased bone strength resulting from low bone mass abs microarchitectural deterioration of bone tissue
- increased susceptibility to fragility fractures (minimal or no trauma fx)
NORMAL CALCIUM
NORMAL PTH
NORMAL PHOSPHORUS
Risk factors: Caucasian Female Postmenopausal Old age Sedentary Low body weight Poor Ca and D intake Alcohol and tobacco use Premature menopause Steroid use
Surface ectoderm
Anterior pituitary (Rathke pouch) Lens and cornea Inner ear, olfactory epithelium Nasal and oral linings, salivary glands Epidermis, sweat, mammary glands
Thoracic aortic aneurysm
Marfan syndrome (idiopathic cystic medial degeneration)
Direct factor Xa inhibitor MOA
Ie apixaban
Directly block Xa active site—> reduced conversion of PROTHROMBIN TO THROMBIN
Oral, no drug level monitoring needed
Alternative complement pathway
Auto activated C3b continually forms in intravascular space and is rapidly inactivated by healthy cells
In presence of microbes or damaged cells—> C3b production amplified, engages with factor B and factor D to generate C3 convertase
Staphylococcal toxic shock syndrome (TSS)
Superantigen that binds to MHCII complex of APCs without processing and no specifically activate T cells—> dramatic release of inflammatory cytokines—> hypotension, high fever, organ failure, rash
Classic galactosemia
GALT deficiency
AUTOSOMAL RECESSIVE
Accumulation of galactose 1 phosphate—> TOXIC METABOLITE that causes renal and liver dysfunction
Vomiting, lethargy, failure to thrive
Can predispose neonates to E. coli sepsis
Bethanechol
Cholinergic agonist
Stimulates peristalsis in post op ileus and non obstructive urinary retention (atonic bladder)
TCA cycle alpha ketoglutarate to succinyl coA releases
NADH and CO2
Autoimmune hepatitis histology
Lymphocyte and plasma cell infiltration of portal and peripheral regions of liver
MC in women
+ anti smooth muscle antibody
Hypergammaglobulinemia
Maternal rubella infection
Maculopapular rash with head to toe progression
JOINT PAIN
Postauricular LAD
Transplacental transmission to fetus causes CONGENITAL RUBELLA SYNDROME
- sensorineural deafness
- cataracts
- PDA
- microcephaly
- growth restriction
Vitamin B7 (biotin)
Cofactor in CARBOXYLATION RXNS (add 1 C)
1 pyruvate carboxylase- gluconeogenesis
2 acetyl co A carboxylase- FA synthesis
3 propionyl co A carboxylase- odd chain FA
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
Kidney blood flow auto regulation (2 mechanisms)
- Myogenic response- AFFERENT glomerular arterioles reflexively constrict when they sense greater stretch forces (HIGH BP)
- Tubuloglomerular feedback- high arterial pressure causes hyperfiltration (high GFR), increasing Na and Cl delivery to macular densa, which secreted vasoactive mediators (adenosine) to constrict AFFERENT ARTERIOLES
- protects organs from persistent high BP
- in patients with long standing HTN, there is baseline afferent arteriolar constriction, causing renal auto regulation to right shift: HTNsive patients kidneys receive less blood flow at any given BP therefore quickly lowering the BP to normal—> causes steep drop in blood flow, leading to relative ischemia (bump in act, granular casts in urine, AKI)
C botulinum toxin MOA
Heat resistant spores
Prevents ACh release at NMJ (no muscle contraction)—> floppy paralysis
Dx caused by spore INGESTION
Many variants of toxin produced—> carried by BACTERIOPHAGES NOT IN DNA OF BACTERIA
Diffuse large B cell lymphoma
MOST COMMON NH LYMPHOMA
B cell malignancy- CD19 and CD20+
Most cells express Ig
Occurs in older adults
OCCURS IN HIV PTS with low CD4 count
- AIDS defining illness
TREAT WITH RITUXIMAB- mab CD20 ab. Used in CD20+ B cell lymphomas (diffuse large B cell, follicular)
Sotalol risk
Anti arrhythmia III
- blocks K channels in phase 3
Risk of TORSADES DE POINTES, EXCESSIVE BETA BLOCKADE
Expansive population pyramid
High birth rates
High mortality rates
Short life expectancy
Growing population
Developing countries
Anterior horn
Motor nerves
Cataracts
Opacification of LENS
Poliomyelitis
Unvaccinated child, febrile illness, neuro symptoms 4-5 days later
Weakness (legs>arms)
Flaccid muscle tone
Polio causes destruction of cells in anterior horn
Congenital CMV
Blueberry muffin baby
Seizures
Hepatosplenomegaly
Newborn deafness
Acute radiation induced lung injury
Radiation damage primarily affects alveolar capillary barrier
—> inflammatory response with cytokine cascade (IL1, TNF a) and growth factors (PDGF, TGFb)
Acutely- hyaline membrane formation, exudative alveolitis
Cough and dyspnea
Sepsis organ dysfunction driven by:
POOR TISSUE OXYGEN USE
3 major mechanisms:
1. Bacterial components and acute phase cytokines trigger production of free radical that damage mitochondria and interfere with ETC—> mitochondrial dysfunction causes decreased oxidative phosphorylation with loss of ATP and shift toward glycolysis which causes lactic acidosis
- Microcirculatory failure with vasodilation —> blood shunts rapidly thru organs, decreasing opportunity for O2 extraction
- Increased capillary permeability causes tissue edema—> increases diffusion distance for oxygen to reach mitochondria of target cells
Ketamine MOA and AE
NMDA ANTAGONIST
Rapid induction anesthesia, short acting
PRESERVES RESPIRATORY DRIVE and PROVIDES ANALGESIC EFFECT
Ketamine stimulates release of catecholamines (ie sympathomimetic) which causes BRONCHODILATION, but will increase HR, myocardial contractility, and cerebral blood flow—> puts pts at risk for CV events or INCREASED INTRACRANIAL PRESSURE
Bulimia nervosa
Recurrent binge eating episodes and INAPPROPRIATE COMPENSATORY MECHANISMS (fasting, excessive work out)
Pts are NORMAL or overweight
Neural crest derivatives (CALMEST POSE)
Cranial bones Adrenal medulla Leptomeninges— Pia and arachnoid Melanocytes Enterochromaffin cells Tracheal cartilage
PNS ganglia (Schwann cells) Odontoblasts Spiral membrane— aorticopulmonary septum Endocardial cushions
Cranial nerves 3-12
Neuroblastoma
Common malignancy in chemistry under 5
Arises from NCC that populate adrenal medulla and sympathetic chain
Mutation in tumor suppressor, MYCN
- poor prognosis
ASYMPTOMATIC ABDOMINAL MASS CROSSING MIDLINE
Histo- small blue cells forming Homer Wright peudorosettes (rings of tumor cells that surround tumor nerve fibers)
Porphyria cutanea tarda
MC porphyria, defective heme synthesis that leads to accumulation of heme precursors
Usually ACQUIRED DEFICIENCY OF UROPORPHYRINOGEN DECARBOXYLASE
- familial
- HCV
Accumulation of UROPORPHYRIN —> tea colored urine
PHOTOSENSITIVITY- blisters, shearing of skin in sun exposed areas, and hyperpigmentation
EXACERBATED BY ALCOHOL, HIV, HCV
Treat- PHLEBOTOMY, AVOID SUN, ANTI MALARIALS (hydroxychloroquine)
Cluster C (anxious/fearful) 3
- Avoidant- avoidance due to fears of criticism and rejection
- Dependent- submissive, clingy, needs to be taken care of
- Obsessive- compulsive- rigid, controlling, perfectionist
Pharyngeal arches 3 and 4
Contains mesoderm
Arch 3- aortic arch, common carotids, and internal carotids
Arch 4- aortic arch and subclavian artery
Hyper IgM syndrome
Defect in CD40L on CD4 T cells. —> prevents B cells from class switching
Clinically- recurrent sinopulmonary, GI (Giardia), minimal lymphoid tissue, and opportunistic infections
High IgM, low/absent IgG/IgA/IgE
PCN type II HSR
Hemolysis
- PCNs bind to surface of RBCs—> abs against PCN bound to RBCs
- direct Coombs test +
IgG mediated
Tyrosine is a precursor of (5)
- Thyroxine
- Dopamine
- Epinephrine
- NE
- Melanin
Non African plasmodium
P. Vivax and ovale
Dormant hepatic stage and can cause recurrent parasetemia
Tx with chloroquine (erythrocyte phase) and primaquine (dormant hepatic stage)
Chromosome 22q11.2 micro deletion
DiGeorge syndrome:
- cardiac abnormalities
- hypoplastic/absent thymus
- hypocalcemia
Velocardiofacial syndrome
- cleft palate
- cardiac anomalies
- dystrophin facies
Thyroglossal duct cyst
Midline mass that moves superiorly with protrusion of tongue and swallowing
Lissencephaly
Sulci of brain and gyri of cerebral cortex absent/decreased
Caused by FAILURE OF NEURONAL CELL MIGRATION from germinal matrix of cerebral ventricles
Congenital Zika can cause microcephaly, lissencephaly, seizures, facial/ocular abnormalities, hearing loss
S/s feeding issues, psychomotor retardation, devo delay, seizures, failure to thrive
Omalizumab
Anti IgE antibody
- inhibits IgE binding to mast cells, preventing mast cell degranulation
Used in patiens with severe, persistent asthma to lower IgE levels and reduce allergen induced bronchial constriction
PNH
Caused by outa toon in hematologist stern cells that eliminates production of anchoring protein that attaches surface molecules to cell membrane
Loss of membrane anchor prevents RBCs from expressing COMPLEMENT INACTIVATING SURFACE PROTEINS CD55/59
- without these proteins, auto activated compounds of ALTERNATIVE COMPLEMENT PATHWAY cannot be disabled
- this leads to complement amplification and generation of MEMBRANE ATTACK COMPLEXES on RBC membrane and subsequent complement mediated hemolysis
Treatment with ECULIZUMAB targets C5 (first complement protein to contribute to MAC) can drastically reduce hemolysis and improve symptoms
HOWEVER- MAC is crucial for defense against encapsulated bacteria (NEISSERIA)
Pts on anti C5 therapy require vaccination against encapsulated bacteria and abx prophylaxis (PCN) to prevent fulminant infection
Binge eating disorder
Recurrent episodes of binge eating
No inappropriate compensatory behaviors
Lack of control during eating
Li Fraumeni syndrome
Syndrome of multiple malignancies at early age
(Sarcoma, breast, leukemia, adrenal gland- SBLA cancer syndrome)
Mutation in tumor suppressor gene TP53- codes for p53
Mutation: cell cycle not arrested to allow for DNA repair and CELLS FAIL TO UNDERGO APOPTOSIS
Accumulation of damage—> malignancy
C tetani toxin MOA
Tetanospasmin blocks release of GABA and glycine from Renshaw cells in spinal cord
Spastic paralysis
Tx w metronidazole, tetanus Ig, benzodiazepines, tetanus toxoid vaccine
Aldosterone escape
Evasion of the Na retaining effects of inappropriately elevated aldosterone levels in conditions such as primary hyperaldosteronism or congestive heart failure
Mechanism: sodium and water retention → volume expansion → secretion of atrial natriuretic peptide (ANP) and pressure natriuresis → compensatory diuresis → “escape” from edema formation and hypernatremia
IgA protease
Enzymes thy cleave and INACTIVATES IgA
Protease allows for colonization of mucosal surfaces
Streptococcus pneumonia
Haemophilus influenzae type b
Neisseria sp
BRAF proto oncogene
Ras signal transduction
Hairy cell leukemia
Melanoma
Respiratory changes with normal aging (4)
- Increased physiological dead space (lung elastin degrades, resembles emphysema)
- Microatelectasis dt remodeling of muscles of inspiration (lower peak force for coughing, deep inspiration)—> intrapulmonary shunting
- Greater V/Q mismatch—> increased alveolar- arterial (Aa gradient)
- PaO2 falls dt high Aa gradient
PaCO2 not significantly changed
Why is TMP SMX not used in pregnancy
TMP SMX crosses BBB and displaces bilirubin from its albumin binding site—> accumulation of unconjugated bilirubin—> jaundice, kernicterus
Classic galactosemia
GALT deficiency
AUTOSOMAL RECESSIVE
Accumulation of galactose 1 phosphate—> TOXIC METABOLITE that causes renal and liver dysfunction
Vomiting, lethargy, failure to thrive
Can predispose neonates to E. coli sepsis
Digoxin and loop diuretic interaction
Hypokalemia contributes to digoxin toxicity by allowing digoxin to inhibit Na K ATPase more effectively
Loop diuretics cause hypokalemia and hypomagnesemia
Phenytoin induces P450s abs leads to DECREASED digoxin levels
Metformin MOA
- Reduces hepatic gluconeogenesis and release of glucose into serum and reduces glucose uptake from intestines
- Increased insulin dependent peripheral glucose uptake and utilization
- Reduces circulating lipid levels
Circulating insulin is unchanged
Above pectinate line
Blood supply- SUPERIOR RECTAL ARTERY (IMA branch)
Venous- superior rectal vein—> inferior mesentery vein—> PORTAL SYSTEM
Lymph drainage- INTERNAL ILIAC NODES
Visceral innervation (no pain)
- internal hemorrhoids
- ADENOCARCINOMA
Primitive ventricle
Trabeculated part of LV and RV
Bacteria with polypeptide capsule (1)
Bacillus anthracis
Capsule is D GLUTAMATE
Limits/ prevents phagocytosis
Fibrates AE
Cholelithiasis: fibrates inhibit cholesterol 7α hydroxylase → decreased bile acid synthesis → supersaturation of bile with cholesterol (↑ cholesterol:bile acid ratio)
AE of acetylcholinesterase inhibitors (donepezil, rivastigmine)
Enhanced parasympathetic tone —> bradycardia and AV block, reduced CO and syncope
Pyruvate kinase deficiency
AR- males and females equally affected, consanguinity increases incidence of autosomal recessive condition
Deficient pyruvate kinase—> RBCs unable to produce sufficient ATP to maintain normal plasma membrane NaK ATPase activity—> RBCs swell and lyse
Echinocytes on smear
Fatigue, pallor, scleral icterus, jaundice, splenomegaly (extravascular hemolysis)
Histadine precursor of
Histamine
Serum sickness
Tissue deposition of circulating immune complexes (TYPE III HSR)
Fever, rash, arthralgia 7-14 days after antigen exposure
Bx shows:
1. Fibrinoid necrosis of small vessels with neutrophil infiltration
- Hypocomplementemia (decreased C3/C4)—> deposition of IgG/IgM complement fixing abs causing complement consumption
Can occur after administration of chimeric monoclonal antibody (infliximab), non human immunoglobulins (venom anti toxins), certain non protein drugs—> PCN, cefaclor, TMPSMX
Uric acid precipitates where
Uric acid is soluble at physiologic pH, but precipitates in ACIDIC environment
The lowest pH in nephron is in DCT and CD—> these segments can become obstructed by uric acid crystals
Obstructive utopia they and acute renal failure follow
Fab
Antigen binding fragments
Contain variable domain and first constant region of heavy and light chain
DO NOT CONTAIN Fc region, therefore DO NOT ACTIVATE complement of trigger phagocytosis via Fc receptor on macrophages
Fab fragments used in immunotherapy have greater tissue penetration and pharmacokinetics because they are smaller fragments
Ventral mesentery
Derived from septum transversum
Only exists between esophagus, STOMACH, upper duodenum
In adult:
- connection between liver and anterior abdominal wall—> Falciform ligament
- connection between liver and stomach—> lesser omentum
10 granulomatous diseases
Tb Sarcoidosis Crohns Leprosy Cat scratch disease (Bartonella henslae) Schistosomiasis Syphilis Temperal arteritis CGD Listeria monocytogenes
Anaplastic thyroid cancer
Associated with p53 mutations
Cells produce inactive p53–> uncontrolled cell growth
Carbon tetrachloride mechanism of liver damage
Causes free radical injury
CCl4 oxidized by P450 system—> free radicals that reacts with structural components of lipid membrane —> lipid degradation and hydrogen peroxide formation (LIPID PEROXIDATION)
CCl4 cell injury is rapid and leads to swelling of endoplasmic reticulum, mitochondria destruction, increased cell membrane permeability
—> culminates in hepatic necrosis
P450 inhibitors
Amiodarone Cimetidine Flurorquinolones Clarithromycin Azole antifungals Grapefruit juice INH Ritonavir (protease inhibitors)
Carotid sinus massage MOA
Leads to increase in parasympathetic tone causing temporary inhibition of SA node activity, slowing conduction through AV node and prolongation of AV node refractory period
Useful to terminate paroxysmal supraventricular tachycardia
NMDA receptor
An ionotopic receptor that depolarizes the neuron when activated by glutamate (and glycine less frequently). Critical for controlling synaptic plasticity and memory function. Overactivation can cause excitotoxicity and cell death.
GLUT1
Insulin INDEPENDENT glucose transporter - uptake when glucose high
BRAIN
RBC
Spina bifida quad screen
INCREASED AFP
Normal bHCG, inhibin A,unconjugated estriol
Connection between spinal canal and amniotic cavity dt failure of anterior and posterior neuro pores
NTD also associated with HIGH ACETYLCHOLINESTERASE in amniotic fluid- results from fetal CSF leakage
Neuroleptic malignant syndrome
Hyperthermia
Muscular rigidity
AMS
autonomic dysfunction (tachy, diaphoresis, labile BP)
Caused by dysregulation of dopamine
- antipsychotics block dopamine (dopamine antagonists)
Actinic (solar) keratosis
Precursor to SCC
Testicular tumor
Seminoma (malignant, radiosensitive)
High placental ALP
Methotrexate
TMP
Pyramethamine MOA
Inhibit dihydrofolate reductase—> decreased thymidine in humans, bacteria, protozoa
P450 inhibitors (7)
More dangerous, risk of toxicity
Cyclosporine INH erythromycin cimetidine Azoles grapefruit juice Ritonavir
External iliac LN drainage
STIs
Mets
C5a and IL8 and IgG
Chemotactic for neutrophils
GBS special features
Produces CAMP factor- enhances beta hemolysis when streaked with S aureus
Hippurate test +
Screen 35-37 week pregnant women for GBS- if positive give PCN
Can cause sepsis, meningitis, PNA in newborns
Synergistic
Effect of substance A and B together is greater than sun of their individual effects
Clopidogrel with aspirin
Malate to OAA releases
NADH
Serotonin syndrome
AMS (disorientation) Autonomic hyperactivity (hyperthermia, tachycardia, diaphoresis) Neuromuscular excitation (hyperreflexia, clonus, tremor)
Caused by excessive serotonin activity, MC dt SSRI + another serotonergic agent
Basal cell carcinoma
Pearly, waxy nodule with nonhealing central ulceration, telangiectasias
Malignant cells derive from STRATUM BASALE (deepest layer of epidermis. Undergoes most cell division)
Malignant cells form dermal nests with peripheral nuclear palisading
Sun exposed areas of head, neck, upper trunk, rarely metastasizes
Monoamine oxidase
Enzyme in presynaptic nerve terminals that breaks down monoamine neurotransmitters (serotonin, NE, dopamine)
MAOIs: irreversibly bind and inhibit MAO—> increased presynaptic availability of monoamine neutransmitters and increase their release into synaptic cleft
- need washout period before starting SSRI to reduce risk of Serotonin Syndrome
PHENELZINE
TRANYLCYPROMINE
SELEGILINE
Hereditary/senile amyloidosis
AD inheritance/age related deposition
Transthyretin (prealbumin)—> mutation/aging —> amyloid transthyretin (mutated) ATTRm in hereditary OR amyloid transthyretin (wild type) ATTRwt in senile
Heart, peripheral nerves, ligaments (carpal tunnel)
Nucleotide excision repair
Removes pyramidine dimers caused by UV damage
Specific endonuclease complex detects abnormality —> nicks damaged strand on both sides of pyrimidine dimer and defective region is excised
Mutations in nucleotide excision cause XERODERMA PIGMENTOSUM (severe photo sensitivity and skin cancer at young age)
Medication to keep PDA open in neonate with Transposition of great vessels?
Alprostadil (PGE1 )
Ehrlichiosis
Ehrlichia, vector is tick
MONOCYTES WITH MORULAE (mulberry like inclusions in cytoplasm)
Non specific symptoms:
- fever, chills, myalgia, macularpapular rash, LYMPHOPENIA
- elevated liver enzymes
CD8 T cells
Cytotoxic T cells
Kill viral infected cells and tumor cells
Parathyroid chief cells
PTH production and secretion
PTH normally maintains calcium homeostasis via PTH mediated increases in bone resorption, renal calcium absorption, and phosphate excretion
Acute stress disorder
Exposure to actual or threatened trauma
Intrusive memories, nightmares, flashbacks with intense psychological/physiological reactions
Amnesia for event, detachment, avoidance of reminders
Negative mood, dissociative symptoms
Arousal with sleep disturbance, irritability, hypervigilance, exaggerated startle, impaired concentration
LASTS MORE THAN THREE DAYS AND LESS THAN 1 MONTH
MC shoulder dislocation
Displacement of humeral head anterior and inferior
Causes axillary nerve injury
- impaired shoulder abduction
- loss of sensation over lateral arm
Axillary nerve provides MOTOR innervation to deltoid and teres minor and SENSORY to skin overlying deltoid
Wide S2 splitting
Seen in conditions that delay RV emptying
- pulmonic stenosis
- RBBB
Causes delayed pulmonic sound (on inspiration)
Alpha 2 second messenger
cAMP
- alpha 2 stimulation—> DECREASED cAMP
- CNS sympatholytic
- decreased insulin release, decreased intestinal motility
Vencuronium
Non depolarizing skeletal muscle relaxant that competitively blocks NICOTINIC ACETYLCHOLINE RECEPTOR
Effect is reversed with AChE inhibitor such as neostigmine because increased ACh will compete with vencuronium at receptor
Cystic fibrosis mutation
Deletion of Phe508 on chromosome 7
Squamous cell carcinoma
Smoking associated
Tumor is located CENTRALLY ALONG BRONCHIAL TRACT
May cause cavitary lesion with central necrosis
If tumor arises in upper lung lobe, can extend peripherally to apex, erode adjacent structures, and cause signs of Pancoast tumors (assoc with Horner syndrome, pain in ULNAR NERVE distribution dt brachial plexus compression, superior vena cava syndrome, and erosion into vertebral structures)
Macrophages release
IL1, TNF a
IL6, IL 8, IL12
Myasthenia gravis
Caused by auto antibody-mediated T cell dependent attack on ACh RECEPTORS OF POST SYNAPTIC NEUROMUSCULAR JUNCTION
- ab mediated blockade of active site of AChRS prevents ACh from binding and triggers endocytosis of AChRs (receptor internalization) and complement mediated post synaptic membrane damage
—> REDUCED NUMBER OF AChRs and impaired neuromuscular blockade
Acquired autoimmune disorder characterized by fatigue, fluctuating weakness of skeletal muscle
MC affected muscle are OCULAR, BULBAR (dysarthria, fatigue when chewing), facial (loss of smile), proximal (neck/shoulder) weakness
RESPIRATORY FAILURE CAN OCCUR DT DIAPHRAGM WEAKNESS
Tx: PYRIDOSTIGMINE: Inhibit AchE → ↓ breakdown of ACh → ↑ ACh levels
Transformation vs. transduction
Transformation- bacterial cell takes up naked, exogenous out DNA and incorporates into genome
Transduction- bacteriophage (virus) transfers DNA from one bacterial cell to another. How bacteria acquire virulence and abx resistance
Mycophenolate
Immunosuppressant
Inhibits IMP dehydrogenase
- less guanine nucleotides for T and B cell replication
Phase II
Methylation
Glucuronidation
Acetylation- slow acetylators have high side effects Bc if low rate of metabolism (INH, sulfasalazine, procainamide, hydralazine)
Sulfation
Polar metabolites
Glioblastoma
MC primary cerebral neoplasm in adults
Derives from ASTROCYTES, GFAP +
Located in CEREBRAL HEMISPHERES, can cross corpus callosum- “butterfly glioma”
Soft, poorly defined margins with areas of NECROSIS and HEMORRHAGE
Highly malignant. Less than 1 year survival.
Ring enhancing on MRI
Pioglitazone
Thiazolidinedione
Activates transcription regulator PPARgamma, decreased insulin resistance
AE- fluid retention/heart failure, WEIGHT GAIN
Primary biliary cirrhosis
Biliary cirrhosis without extra hepatic obstruction
INTRAHEPATIC DUCTS
AUTOIMMUNE DX
- T CELL ATTACK ON intralobular bile ducts
- GRANULOMATOUS INFLAMMATION
ABSENCE OF BILIARY OBSTRUCTION
MC in FEMALES
- FATIGUE AND ITCHING (obstructed bile ducts—> impaired bile acid excretion—> bile acids deposit in skin and cause ITCHING
Pruritis often precedes development of jaundice
+ ANTI MITOCHONDRIAL ABS,
MARKEDLY ELEVATED ALK PHOS
Pneumocystis jirovecii
Fungus, PNA in immunocompromised
AIDS defining illness
Dx BAL with SILVER STAIN
Tx with TMPSMX, pentamidine, dapsone
PROPHYLACTIC TMP SMX when CD4 count <200
Valproic acid MOA
Blocks Na channels and INCREASES GABA levels
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
Arterioles
HIGHEST RESISTANCE TO FLOW
Pressure change will always be greatest across arterioles
Major determinant of TPR
- vasoconstriction - high TPR
- vasodilation - low TPR
Follicular lymphoma
t(14;18)
BCL2 overexpression—> apoptosis evasion
Non Hodgkin’s lymphoma derived from germinal center B cells
Painless, slow growing, waxing and waning LAD IN MIDDLE AGED/ELDERLY
Bullous pemphigoid
Primitive, tense bullae, NO MUCOSAL INVOLVEMENT
SUBEPIDERMAL CLEAVAGE
DEPOSITION OF IGG AND COMPLEMENT AT DERMAL EPIDERMAL JUNCTION
autoantibodies against hemidesmosomes
Negative Nikolsky
Ethambutol
Inhibits arabinosyl transferase
AE- optic neuropathy
ERBB2 (HER2) proto oncogene
Receptor tyrosine kinase
Breast and gastric carcinoma
Cryptococcus neoformans
Opportunistic FUNGAL infection
Meningitis in HIV/AIDS
In soil and pigeon droppings
Heavily encapsulated—> halo with India ink
Can be cx on Sabourad agar
Stains with mucicarmine (red inner capsule)
Latex agglutination test—> detects polysaccharide capsular antigen
CAUSES HIGH ICP AND RISK OF BRAIN HERNIATION WITH LUMBAR PUNCTURE
Sometimes need intrathecal tx
Mets to brain
Lung, breast, melanoma/colon/kidney
Buerger disease (strongly associated with tobacco)
Recurrent inflammation/thrombosis of small/medium vessels in extremities
Malignant ovarian tumor
Serous cystadenocarcinoma
Nissl stain
Aniline dye that stains RNA blue
High affinity for polyribosomes in cytoplasm and on RER
Ribosomal RNA are basophilic
GLUT5
Fructose transporter via Facilitated diffusion.
Zero order elimination
Constant rate of elimination per time
No dependence/variation with concentration of drug
No constant half life
PEA- phenytoin, ethanol, aspirin
CAPACITY LIMITED ELIMINATION
Celiac, SMA, IMA LN drainage
Colon cancer
IBD
NOD receptors
Intracellular receptors that can bind peptidoglycan and will cause cytokines release
Innate IS
6 impt macrophage receptors
- CD14- LPS
- Fc receptor- Fc on abs
- C3b receptor- C3b complement
- MHCII- binds CD4 on T cell
- B7- binds CD28 on T cell
- CD40- CD40 ligand on T cell
High altitude pulmonary edema
Dyspnea, hypoxemia, patchy alveolar infiltrates several days after arrival at high altitude
Pathophys- driven by reduced partial pressure of oxygen—> hypoxia pulmonary vasoconstriction and INCREASED subsequent pulmonary arterial pressure —> alveolar capillary membrane disruption causing patchy, bilateral pulmonary edema
Clearance calculation
0.7x (Vd/t1/2)
2 drugs that cause autoimmune hemolytic anemia
Methyldopa abd PCN
Mycoplasma PNA can also cause autoimmune hemolytic anemia
Cell membrane lysis toxins
C perfringens- alpha toxin- phospholipase (lecithinase) that degrades cell membranes and tissues —> myonecrosis (gas gangrene) and double zone of hemolysis
S pyogenes- streptolysin O- protein that degrades cell membrane- lyse RBCs, contributes to beta hemolysis, HOST ABS against toxin (ASO) used to dx rheumatic fever
Superantigens causing shock
Staph aureus- TSST1, scalded skin (exfoliative toxin), toxic shock, food poisoning (heat stable enterotoxin)
Streptococcus pyogenes- erythrogenic exotoxin A—> scarlet fever, rash, fever, shock
Both cross link beta region of TCR to MHCII on APCs outside of ag binding site—> OVERWHELMING RELEASE OF IL1 IL2 TNF a IFN —> cause SHOCK
Type II pneumocyte functions (2)
- Regeneration of alveolar lining following injury
2. Surfactant production
Ethambutol MOA
Anti Tb agent
Inhibits mycobacterial arabinosyl transferase- necessary for mycobacterial cell wall
AE: blindness, optic neuritis, vision changes
Lesser omentum contents
Contains hepatoduodenal ligament of its free edge
- contains:
1. Hepatic artery proper
2. CBD
3. Portal vein
Cori disease
Glycogen debranching enzyme deficiency —> alpha 1,6 glucosidase deficiency
Hepatosplenomegaly, hypoglycemia, failure to thrive, recurrrent infections in childhood
Short outer branches, single glucose residue at outer branch—> LIMIT DEXTRIN LIKE STRUCTURES ACCUMULATE IN CYTOSOL
CN XII
Innervates intrinsic and extrinsic tongue muscles
Lesion to CNXII causes hemipralysis of tongue—> protrusion causes the tongue to point to weak (lesion) side because of unopposed action of opposite genioglossus
Erythema multiforme
Acute immune mediated condition affecting skin and mucus membranes
TYPE IV HSR- cytotoxic CD8 cells attack basal epithelial cells —> vesicles and erosions in skin and mucosa (macules, vesicles, bullae, and papules)
Most characteristic- TARGERTOID LESIONS (central necrosis surrounded by erythema) on hands and soles
ASSOCIATED WITH PRECEDING MYCOPLASMA OR HERPES SIMPLEX VIRUS
- characteristic hemorrhagic crusting of vermilion borders of lips
Complete androgen insensitivity syndrome
Caused by androgen receptor defect
Patients have normal male genotype (46XY), normal F phenotype, abdominal testes, short vagina, absent ovaries/uterus
SPARSE PUBIC HAIR
Nontyphoidal Salmonella (S. enterica)
Poultry/eggs, exotic pets
Primarily FOODBORNE
Industrialized countries
Invades enterocytes—> NEUTROPHIL MEDIATED INFLAMMATORY RESPONSE IN LAMINATE PROPRIA/ PEYERS PATCHES—> controls infection
Gastroenteritis- self limited watery diarrhea, risk of OSTEOMYELITIS, MYCOTIC ANEURYSM, ENDOCARDITIS
Ureteric buds give rise to
Collecting system of kidney
- collecting tubules, ducts
- major and minor calyces
- renal pelvis
- ureters
DNA pol I
Removes primer via 5’ to 3’ exonuclease activity and replaces them with DNA via 5’ to 3F’ polymerase activity
DNA pol I is only polymerase to possess 5’ to 3F’ exonuclease activity
Meropenem
Least risk of seizures
Carbapenems have risk of seizures
Corticospinal tract
Descending
Motor
Orbitofrontal cortex injury
Personality changes, disinhibition, irritability secondary to impairment of behavioral and emotional modulators systems
Radial nerve motor function (3)
- Extension at elbow, wrist, fingers
- Forearm supination
- injury of radial nerve at supination causes finger and thumb extension weakness - Thumb abduction
Inhaled corticosteroids mechanism in improving asthma
- Reduce inflammation by inhibiting inflammatory genes
- Potentiate the bronchodilatory effects of b2 adrenergic agonists (albuterol)
- steroids upregulate b2 receptors on bronchial smooth muscle
Dinopristone
PGE2 analog given to promote cervical ripening
Increases proteoglycan content and changes collagen properties in cervix, can cause uterine contractility
b2 receptors where
Liver, muscle, bronchioles
Dilate vessels, bronchodilator
b2 block does not lower BP
Blastomycosis
Eastern central US, Great Lakes
BROAD BASED BUDDING
Disseminates to BONE (OSTEOMYELITIS), SKIN LESIONS, slow onset PNA
Amphotericin B for systemic, local fluconazole/itraconazole
Tuberculoid leprosy
Caused by Mycobacterium leprae. Likes cool temperatures—> infects skin and superficial nerves (stocking and glove loss of sensation). Cannot be grown in vitro
Tuberculoid leprosy- LIMITED to few hypoesthetic hairless skin plaques, HIGH CELL MEDIATED IMMUNITY with Th1 response and LOW BACTERIAL LOAD
Granulomas dt strong Th1 CMI response
Wilms tumor
Common renal malignancy in peds
Painless, palpable abdominal mass that DOES NOT cross midline
Causes HTN (dt renin secretion) and hematuria
Associated with WAGR syndrome: Wilms tumor Aniridia GU malformation Retardation
Deletion of WT1 gene - transcription factor for normal GU development
Tx: vincristine/vinblastine (AE neuropathy)
Estrogen and effects on FSH and LH
In follicular stage, estrogen suppresses FSH and LH through negative feedback inhibition of hypothalamus- pituitary- ovarian axis.
Once plasma levels of estrogen reach critical threshold, the negative feedback loop switches to positive feedback loop and LH and FSH surge occurs. This occurs at the end of the follicular phase.
LH surge causes ovulation
Pathologic findings associated with sarcoidosis
Noncaseating granulomas with EPITHELOID HISTIOCYTES
Multinucleated giant cells of Langerhans
Asteroid bodies
Schaumann bodies
Teres minor
Adduction and external rotation
Axillary nerve
Subscapularis
Adduction and internal rotation
Upper and lower subscapular nerve
Imatinib, dasatinib, nilotinib
TKI of bcr- abl t(9;22) in CML
And c-kit in gi stromal tumors
AE- fluid retention
Marginal cell lymphoma
B cell malignancy
marginal zone of LN forms and expands in chronic inflammation
Often extranodal
LYMPHOMA IN CHRONIC INFLAMMATORY DX
- SJOGRENS
- HASHIMOTOS
- MALToma
Waldonstrom macroglobulinemia
Aka lymphoplasmacytic lymphoma
B CELL LYMPHOMA- tumor cells differentiate into plasma cells—> PRODUCE IGM ABS—> hyperviscosity symptoms
No osteolytic lesions
SPEP- M spoke is IgM
S/s: HYPERVISCOSITY SYNDROME
- sluggish blood flow, sludging
- CNS impairment- HA, dizziness, coma
- VISUAL IMPAIRMENT, RETINAL HEMORRHAGE
- Raynauds
Medical emergency- emergent plasmapheresis
Complications- THROMBOSIS
Granulomas
A pattern of chronic inflammation
Can be induced by persistent T cell response to infections (Tb)
Immune mediated diseases
FOREIGN BODIES
Wall off resistant stimulus without completely eradicating or degrading it—> persistent inflammation
Center of EPITHELOID CELLS (activated macrophages with abundant pink cytoplasm) surrounded by lymphocytes and multinucleated giant cells (formed via fusion of several activated macrophages)
T cell mediated HSR—> type IV, CMI processs
APCs present to CD4 Th cells and secrete IL12–> CD4 differentiates into Th1 cells
Th1 cells secret IFN gamma—> macrophage activation
Macrophages secrete TNFa—> donation of epithelioid macrophages and giant cells
Congenital rubella
Blueberry muffin baby
Cataracts
Congenital heart disease - PDA
Mother acquires infection via respiratory droplets
- rash, fever, LAD
Haptoglobin
Plasma protein that binds free Hb
Haptoglobin- hb complex cleared by liver
Low serum haptoglobin with intravascular hemolysis
Below pectinate line
Blood supply- INFERIOR RECTAL ARTERY (branch off pudendal artery (off iliac))
Venous- inferior rectal—> internal pudendal—> internal iliac—> IVC
lymph- superficial iliac nodes
Somatic innervation
- painful
- external hemorrhoids
SQUAMOUS CELL CARCINOMAS (more common Anal ca)
Imperforate anus
Hindgut and ectoderm need to meet to firm anus—> if fails to happen—> absence of anal opening—> imperforate anus
Commonly associated with GU malformations
- renal agenesis
- bladder exstrophy
S/s
- failure to pass meconium
- meconium from urethra/ vagina (fistula)
Femoral nerve
Forms within psoas major muscle from posterior divisions of anterior rami L2-L4
Femoral nerve lies in the groove between psoas major and iliacus
Femoral nerve innervates all of the muscles of the anterior compartment of thigh—> hip flexors abs knee extenders
Proto oncogene activation
Stimulation of cellular proliferation
Gain of function mutation
Requires damage to one allele
t(8;14)
Burkitt lymphoma (c myc fusion, transcription factor oncogene)
Giemsa stain
Stains nucleic acids—> gets inside cells
Rickettsia Chlamydia TRYPANOSOMES Plasmodium Borrelia H pylori
Dobutamine
Sympathomimetic: b1> b2, a
INCREASE HR, INCREASE CO, no change/lower bp
Used in HF, cardiogenic shock (+inotrope), cardiac stress testing
Triptans MOA
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
DECREASE NEUROGENIC INFLAMMATION
DECREASE CGRP RELEASE
VASOCONSTRICTION
DVT treatment in pregnancy
Heparin
- LMWHs: dalteparin, enoxaparin
Heparins DO NOT cross placenta
Cord factor
M Tb virulence factor
Prevents phagolysosome fusion and acidification —> allows M Tb to replicate in uncheck fashion within phagosome of alveolar macrophage
E cadherin mutation
CDH1 gene, component of adherens junctions
Mutated in gastric adenocarcinoma and infiltrating lobular carcinoma of breast
Humerus fracture causes what nerve damage
Humerus fracture can lacerate RADIAL NERVE
Causes loss of function to the muscles that extend the wrist and digits and sensory loss on posterior forearm and hand
Patients have difficulty stabilizing wrist when attempting to make a fist
S3
High ventricular filling pressure (mitral regurgitation, HF)- sudden deceleration of blood from LA to LV
Common in dilated ventricles- LHF
HLAB27
Psoriatic arthritis
Ankylosing spondylitis
IBD associated arthritis
Reactive arthritis
Death in SLE
Lupus nephropathy
Tabes dorsalis (tertiary syphilis) Subacute combined degeneration (dorsal columns, lateral corticospinal tract, spinocerebellar tract affected)
Degeneration of dorsal columns
Keloids
Hyperproliferation of fibroblasts which results in DISORGANIZED overproduction of hyalinized collagen types I and III
Haemophilis influenzae b prophylaxis
Rifampin
MOA: inhibits bacterial DNA-dependent RNA-polymerase → prevention of transcription (mRNA synthesis) → inhibition of bacterial protein synthesis → cell death (bactericidal effect)
Poststreptococcal glomerulonephritis
Antibodies against streptococcal antigens that deposit in GBM
IF C3 granular staining
EM subepithelial humps
nephritic syndrome
Loading dose
[steady state]x(Vd/F)
Toll like receptors
INNATE IS
Key receptors on macrophages, dendritic cells, mast cells
Recognize PAMPs (LPS, flagellin, nucleic acids) and DAMPs. Leads to activation of NfKB
Schistosomiasis
Parasitic blood fluke infection
Common in sub Saharan Africa
Intial infection asymptomatic, patients later develop chronic hepatosplenic (portal HTN, hepatosplenomegaly, esophageal varies) or urinary (bladder cancer) complications years/decades later
Eosinophilia important diagnostic clue
Cystinuria
AR disorder caused by defective transportation of Cystine, Ornithine, Lysine, Arginine (COLA) across the intestinal and renal epithelium
Excess cystine in urine leads to recurrent precipitation of pathognomonic HEXAGONAL CYSTINE STONES
Tx- alkalinize urine (acetazolamide, potassium citrate) and cheating agents (penicillimine)
Urinary cyanide nitroprusside test diagnostic
Methionine free diet
Urinalysis shows pathognomonic hexagonal cystine crystal
Fecal leukocytes, RBCs usually indicate what type of infection?
Invasive
- bloody diarrhea
Campylobacter, salmonella, shigella, y. Enterolitica, EIEC, entamoeba histolytica, EHEC
Cephalosporins and bleeding risk
Cefotetan, cefazolin- hypoprothrombinemia (low clotting factor levels)
Inhibit epoxide reductase (similar to warfarin)
Decrease hepatic synthesis of clotting factors
- may prolong PT/INR
- reversible with vitamin K
TMP SMX side effects (2)
Hyperkalemia - TMP blocks epithelial sodium channel in DCT and CD—> impairs Na/K exchange —> reduced K excretion and hyperkalemia
Folate deficiency with prolonged use
CO determinants (4)
Preload
After load
Heart rate
Contractility
Brain mets not from primary CNS cancer
Multiple, well circumscribed masses
At junction of grey- white matter
MC mets from lung, breast, kidney, melanoma, colon
IL5
Class switching to IgA
Growth and differentiation of EOSINOPHILS
21 alpha hydroxylase deficiency
MC CAH
Hallmarks are SALT WASTING AND VIRILIZATION
Salt wasting dt inability to synthesize mineralcorticoids- hyponatremia, hyperkalemia, patient becomes dehydrated dt lack of Na
Bacillary angiomatosis vs. Kaposi sarcoma
Both seen in advanced AIDS pts.
Both present with night sweats, weight loss, fevers, violaceous vascular skin nodules
Bacillary angiomatosis- caused by Bartonellla henslae
- Bx: NEUTROPHILIC INFILTRATION AND GRANULOMATOUS CHANGES
Kaposi sarcoma- caused by HHV8, lesions present more on legs/face/genitals
- on bx: SPINDLE CELLS AND LYMPHOCYTIC INFILTRATE
Cholinergic agonists
Increase GI tract smooth muscle tone to produce nausea, vomiting, abd cramps, and diarrhea
Decrease HR, cardiac conduction and contractility, may result in bradycardia, heart block, hypotension
Cholinergic associated peripheral vasodilation decreases BP dt stimulation of endothelial nitric oxide synthesis
Increase secretion, leading to excessive sweating, salivation, lacrimation
Can cause dyspnea via bronchoconstriction (increased smooth muscle tone in trachebronchial tree) and increased bronchial secretion
Mechanism of hypoxemia and hypocapnia in pulmonary embolism
PE leads to increased dead space ventilation with a consequence ventilation/perfusion (V/Q) mismatch that causes HYPOXEMIA.
The acute hypoxemia along with pulmonary parenchymal inflammation triggers an increase in respiratory drive and HYPERVENTILATION
Rate of CO2 removal is closely tied to ventilation rate, alveolar hyperventilation leads to increased expiration of CO2 with resulting hypocapnia (low PaCO2) and respiratory alkalosis
In contrast, rate of O2 absorption becomes capped once hemoglobin is saturated, which occurs at relatively low PaO2 (ie Hb 85% saturated at PaO2 50mmHg). Therefore, blood in highly ventilated lung areas cannot absorb extra O2 to compensate for poorly ventilated regions and hyperventilation does not significantly increase PaO2
Pts with acute V/Q mismatch (PE, PNA) typically have hypocapnia with respiratory alkalosis and persistent hypoxemia
Barr bodies
Inactivated X chromosome
- small perinuclear dark staining dot in somatic cells with two or more X chromosomes
- found in normal females 46XX and 47XXY (Klinefelter syndrome)
Hodgkin lymphoma presentation
Cervical LAD with B symptoms
Spreads predictably —> limited dx highly curable
STAGE IS STRONGEST PREDICTOR OF PROGNOSIS
Bimodal age distribution (20 and 60)
Risk factors:
- Prior EBV infection
- IMMUNOSUPPRESSION (HIV, transplants)
- autoimmune dx- RA, lupus
What does calcium bind for muscle contraction
Calcium releases from sarcoplasmic reticulum binds troponin C—> conformational change in troponin complex, causing it to displace tropomyosin and expose myosin binding sites on actin filaments
Internuclear ophthalmoplegia
Disorder of impaired horizontal gaze caused by a lesion in MEDIAL LONGITUDINAL FASCICULUS (MLF)
Affected eye (same side as lesion) unable to adduct while other eye abducts
Convergence and pupil light reflex preserved
Bacteria associated with gastritis, PUD, gastric malignancies (ie adenocarcinoma, MALToma)
H pylori
Viral encephalitis affecting temporal lobe
HSV1
Reactive arthritis causes
Triad of
arthritis
urethritis (dysuria, urethral discharge, urgency)
conjunctivitis
Autoimmune reaction to previous infection with: Shigella salmonella yersinia campylobacter chlamydia
HLAB27 associated
Mitochondrial inheritance
Occurs in M and F
Inherited thru F only
Compound nevi
Benign proliferation’s of melanocytes that involve BOTH dermis and epidermis
Lesions are slightly raised papules with uniform pigmentations and symmetrical sharp borders
Uniform brown to tan pigmentation
Paget disease of bone (osteitis deformans)
Excessive and disordered bone formation caused by high osteoclastic activity followed by high osteoclastic activity activity that forms poor quality bone
NORMAL Ca, phosphorus, PTH
HIGH ALK PHOS
Mosaic pattern of woven and lamellar bone
- long bone chalk stick fx
- hearing loss dt auditory foramen narrowing
- high output heart failure (from high blood flow thru AV shunts)
- HIGH RISK OF OSTEOSARCOMA (periosteal new bone with lifting of periosteum)
Cardiac tissue conduction velocity (Park At Venture AVe)
Purkinje (fastest)
Atrial myocytes
Ventricular myocytes
AV node (slowest)
DNA laddering
Fragments of 180bp multiples
Sensitive indicator of apoptosis
Laddering arises from the actions of specific endonucleases during karyorrhexis—> cleave DNA IN 180 bp intervals
Apoptosis
Process of cell death that occurs when REGULATING SUBSTANCES (interleukins) withdrawn from proliferating cells
Malignant lymphoid cells evade apoptosis by over expressing BCL2 —> anti apoptotic protein
Paget disease of bone (osteitis deformans)
Excessive and disordered bone formation caused by high osteoclastic activity followed by high osteoclastic activity activity that forms poor quality bone
NORMAL Ca, phosphorus, PTH
HIGH ALK PHOS
Mosaic pattern of woven and lamellar bone
- long bone chalk stick fx
- hearing loss dt auditory foramen narrowing
- high output heart failure (from high blood flow thru AV shunts)
- HIGH RISK OF OSTEOSARCOMA (periosteal new bone with lifting of periosteum)
Cardiac tissue conduction velocity (Park At Venture AVe)
Purkinje (fastest)
Atrial myocytes
Ventricular myocytes
AV node (slowest)
DNA laddering
Fragments of 180bp multiples
Sensitive indicator of apoptosis
Laddering arises from the actions of specific endonucleases during karyorrhexis—> cleave DNA IN 180 bp intervals
Apoptosis
Process of cell death that occurs when REGULATING SUBSTANCES (interleukins) withdrawn from proliferating cells
Malignant lymphoid cells evade apoptosis by over expressing BCL2 —> anti apoptotic protein
Germline mosaicism
Involves only oocytes or spermatocytes
SHOULD BE CONSIDERED WHEN GENETIC MUTATION IDENTIFIED IN OFFSPRING AND NOT PARENTS
Low flow pancreatic exocrine secretion
Low bicarbonate
Higher chloride
High flow pancreatic exocrine secretion
High bicarbonate
Low chloride
Low flow salivary secretions
Higher K
Lower Na and Cl
High flow saliva
Isotonic to plasma
Glucagon receptor
GsPCR
AC/cAMP
Epinephrine receptor
GsPCR
AC/cAMP
Insulin receptor and growth factors
Receptor tyrosine kinase
IP3 pathway
Warm autoimmune hemolytic anemia
Normocytic anemia, unconjugated hyperbilirubinemia, reticulocytosis (large blue RBCs), spherocytosis (caused by phagocytosis of IgG ab and component of RBC membrane creates sphere shaped RBCs on smear)
Chronic anemia in which IgG causes RBC agglutination
CLL- malignant cells produce autoantibodies
SLE
METHYLDOPA
Chronic lymphocytic leukemia
B CELL NEOPLASM
CD20
CD23
CD5
Smudge cells on smear
AUTOIMMUNE HEMOLYTIC ANEMIA!!!!!
Richter transformation- CLL/SLL transformation into aggressive lymphoma —> diffuse large B cell
HAV
Self limiting infection that presents with nausea, vomiting, abdominal pain, icterus, hepatomegaly, RUQ tenderness that evolves OVER SEVERAL WEEKS AFTER INGESTION OF POORLY COOKED, IMPROPERLY HANDLED, RAW FOOD- INCLUDING SHELL FISH
HAV diagnosed by serologic detection of anti HAV IgM abs
Increased A a gradient occurs in
V/Q mismatch
Shunt
Diffusion limitation
Respiratory depression causes
Hypoventilation
- hypoxemia
- respiratory acidosis (dt CO2 retention)
- NORMAL Aa gradient of 10
Ulnar nerve injury
Ulnar nerve innervates INTRINSIC MUSCLES OF HAND
Roots are C8 to T1
Injury causes weakness of abduction and addiction of index, middle, ring, small fingers, loss of wrist flexion, ulnar claw on digit extension
- medial epicondyle fx
- fractured hook of hamate from FOOSH
- Can be injured with traction on brachial plexus
Radial nerve innervation
C5 to T1
Innvervates EXTENSORS of digits, wrist, ABDUCTION OF THUMB
Compression of axilla
Midshaft humerus fx
Repetitive pronation/supination (screw driver) - “finger drop”
Wrist drop- loss of elbow, wrist, finger extension
Decreased grip strength
Loss of sensation over posterior forearm and dorsal hand
Adenosine diphosphate (ADP)
Rapidly and irreversibly causes platelet aggregation thru it’s action on P2Y1 and P2Y2
Measles (rubeola) virus
Paramyxovirus
Prodrome of fever, cough, coryza, conjunctivitis, rash, Koplik spots on buccal mucosa
F fusion protein (virulence factor, aids in viral fusion to host cells)
Can have formation of giant cells
Severe sequelae:
- SUBACUTE SCLEROSING PANENCEPHALITIS (SSPE)
Personality changes, seizures, dementia, motor deterioration, death
- encephalitis
- GIANT CELL PNA (seen in immunosuppressed, inclusion bodies and multinucleated giant cells in respiratory epithelium)
Folate deficiency
Megaloblastic anemia
Hypersegmented neutrophils
Erythrocyte macrocytosis
INCREASED HOMCYSTEINE
normal methylmalonic acid
Lead poisoning
Exposure to lead- eating lead paint, inhalation from industrial work
Lead inhibits heme synthesis via 2 enzymes in RBCs
- ferrochelatase
- ALA dehydratase
Decreased heme synthesis—> microcytic, hypochromic anemia
- normal or low iron studies
- buildup of d ALA and protoporphyrin
Smear: basophilic stippling
- lead inhibits rRNA degradation—> rRNA aggregates in RBCs
Abdominal pain, LEAD LINES, nephropathy, WRIST/ FOOT DROP, neurological effects (Devo delay, behavioral issues
REMOVE SOURCE OF LEAD Can give chealtors: - DIMERCAPROL - EDTA - SUCCIMER
Sideroblastic anemia
Ringed sideroblasts- iron loaded mitochondria seen with Prussian blue stain, peri nuclear ring of blue granules
Usually microcytic, ringed sideroblasts in bone marrow
Caused by FAILURE TO MAKE PROTOPORPHYRIN (no protoporphyrin for iron to bind and make heme therefore get iron accumulation in mitochondria)
Usually secondary to toxin
- alcohol (mitochondrial poison)
- vitamin B6 deficiency (INH)
- lead poisoning
X LINKED - inherited deficiency of ALA synthase
- responds to B6
Microcytic, hypochromic anemia
IRON OVERLOAD (high serum iron, high ferritin)
Low erythrocyte protoporphyrin levels
Microcytic anemias
Some problem producing hemoglobin
LOW IRON
- iron deficiency
- anemia of chronic disease (high ferritin)
LOW GLOBIN
- alpha thalassemia
- beta thalassemia
LOW HEME
- lead poisoning
- sideroblastic
Inhaled anesthetics summary
Onset of action:
- Blood:gas partition coefficient (high= slower onset)
- Solubility in blood (higher = slower onset)
- want less blood solubility for faster onset
Potency
- Oil/gas partition coefficient (higher = more potent)
- higher this coefficient, less of the gas needed - MAC (lower= more potent)
Halothane
Hepatotoxic
- massive liver necrosis, increased AST/ALT
Malignant hyperthermia
- fever, muscle rigidity
- tachycardia, HTN
- muscle damage (high K and CK)
- cause: ryanodine receptos in sarcoplasmic reticulum
- tx with dantrolene (muscle relaxant)
Inhaled anesthetic side effects
Myocardial depression- lowers CO
Respiratory depression
N/V
Increased cerebral blood flow
- cerebral vasodilation
- blood flow goes up
- ICP goes up
Decreased GFR
Enflurane
Lowers seizure threshold
Methoxyflurane
Nephrotoxic
- renal toxic metabolite
Nitrous oxide
Diffusely rapidly into air spaces
CANNOT USE IN PNEUMOTHORAX, ABDOMINAL DISTENSION
Opioid mechanism
Morphine, fentanyl, hydromorphone
Mu receptors
G protein linked, second messenger not known
Increase K efflux from cells—> hyperpolarizes cells—> less pain transmission
Ketamine
PCP derivative (people on PCP can hallucinate, become very violent)
Antagonist of NMDA receptor (activated by glutamate in CNS)
Dissociative drug
- trance like state
- analgesia and amnesia
- FEW CV/ RESPIRATORY EFFECTS
CAN CAUSE HTN, tachycardia
If ketamine used alone as sedative—> EMERGENCE REACTIONS
- pts are disoriented, dreams, hallucinations, can be scary for pts
- administer with MIDAZOLAM to avoid
Etomidate
Modulates GABA receptors
- blocks neuroexcitation
Fast onset of anesthesia, no analgesia
Hemodynamically neutral (good for hypotensive pts)
BLOCKS CORTISOL SYNTHESIS
Used in rapid sequence intubation
Succinylcholine
Paralytic- fast onset and offset
DEPOLARIZING neuromuscular blocker
Strong nicotinic ACh agonist
Not metabolized but AChE
Sustained depolarization—> prevent muscle contraction
2 phases:
- Depolarizing phase—> fasciculations can occur
- Na open and close, become inactivated - Desensitizing phase—> depolarization has occurred, muscle no longer reacts to ACh
NO REVERSAL
AE- HIGH K (caution in BURN and DIALYSIS Pts), MALIGNANT HTN
Non depolarizing neuromuscular blockade (tubocurarine, atracurium, mivacurium, pancuronium, vencuronium, rocuronium)
Competitive antagonists
- compete with ACh for nicotinic receptors and produce paralysis
May cause marked HISTAMINE RELEASE
- hypotension and reflex tachycardia
Can be reversed by flooding synapse with ACh
- done by inhibiting AChE
AChE Inhibitors: Physostigmine Neostigmine Pyridostigmine Edrophonium
HIV 3 structural genes
HIV 2 molecules of RNA
3 structural genes coded for:
- ENV- formed from cleavage of gp160,
- gp120 binds CD4 and either CCR5 (macrophages, early infection) or CXCR4 (T cells, late infection)
- gp41 fusion and entry - GAG (p24 and p17)- capsid and matrix proteins
- POL - reverse transcriptase, INTEGRASE, PROTEASE
Juvenile myoclonic epilepsy
Absence, myoclonic, grand max
Common in kids
Absence seizures first, then myoclonic seizures later, grand mail after
HALLMARK: MYOCLONIC JERKS ON AWAKENING FROM SLEEP, shock like irregular movements in both arms
Glioblastoma
Pseudo palisading tumor cells border focal necrosis
Astrocyte origin, GFAP+
Older age, worse prognosis
Can cross corpus callosum
Meningioma
Common, benign
MC in Females, tumor expresses ESTROGEN RECEPTORS
Occurs near surface of brain - extra axial (external to brain parenchyma), may have dural attachment
Parasagittal meningioma- compresses leg area similar to ACA stroke, classic presentation
PSAMOMMA BODIES- laminated calcifications
Pituitary adenoma
Benign growth of pituitary
Most secrete prolactin—> galactorrhea, amenorrhea, impotence, low bone mass dt estrogen suppression
Headaches and BITEMPORAL HEMIANOPSIA (loss of peripheral vision dt pressure on optic chiasm)
Craniopharyngoma
Derived from Rathkes pouch
- invagination of ECTODERM
- protrudes from roof of mouth and forms anterior pituitary
Often calcified, cystic, CHOLESTEROL CRYSTALS FOUND IN MOTOR OIL LIKE FLUID IN TUMOR
Contains epithelial cells—> appearances similar to developing teeth
CAN CAUSE BITEMPORAL HEMIANOPSIA Bc compresses optic chiasm
Pineal tumors
Rare germ cell tumor
Compress pre tectal area of midbrain
Cause PARINAUD SYNDROME
- PARALYSIS OF UPWARD GAZE
- pseudo Argyll Robinson pupils
Can compress cerebral aqueduct—> hydrocephalus, papillaedema
AICA stroke
Literal pons
Facial droop
Hearing loss
PICA
Lateral medulla
Dysphagia
Hoarseness
ASA stroke
Medial medulla- contralateral motor, tongue deviation
Anterior spine- b/l motor, pain, temp, SPARES VIBRATION AND PROPIOCEPTION
Subclavian steal
Flow reversal in vertebral artery
Caused by stenosis of subclavian artery
BP discrepancy of >15mmHg
Exercise induced LEFT arm ischemia- pain, fatigue, numbness
