UWorld

Common malignancies with bony metastasis

"lead kettle" Prostate Breast Kidney Thyroid Lung

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Post-streptococcal glomerulonephritis

1-3 weeks after impetigo or pharyngeal infection w. group A strep oliguria, hematuria, preoteinuria, edema, HTN no anemia

Spleen red pulp

1. destroys aged and abnormal erythrocytes + serves as emergency store of blood cells and platelets 2. clears circulating bacteria that becomes lodged - has opsonizing antibody especially important in the clearance of encapsulated species

Sickle Cell Anemia manifestations

1. intra and extravascular hemolysis - inc. indirect bilirubin - inc. LDH - dec. haptoglobin 2. vaso-occlusive symptoms 3. infections with encapsulated organisms due to functional asplenia

Ionizing radiation (nuclear accidents, radiotherapy)

AML, CML, papillary carcinoma of thyroid

X-linked recessive interitance

Affected males will always produce unaffected sons and carrier daughters carrier females have a 50% chance of producing an affected son or carrier daughter i.e. pattern of inheritance in G6PD deficiency

Amino Acid Functions and Metabolism

Alanine: metabolized in liver to produce pyruvate Aspartate: interconverted with oxaloacetate Arginine: urea cycle intermediate that helps remove nitrogenous waste from blood - hepatic metabolism results in urea and ornithine HistidineL converted to histamine for acute inflammatory response, gastric acid secretion, and function as neurotransmitter

Screening for early-stage diabetic nephropathy

Albuminuria; administer ACE inhibitors to slow progression (Lisinopril)

Blood pressure medication

Beta-blockers: inhibit renin release by blocking beta-1 receptor mediated regulation or RAAS (dec. renin, ATI, ATII, aldosterone) Direct renin inhibitors: block conversion of angiotensinogen to angiotensin IL reduced angiotensin I and II but inc. renin ACEI: prevent conversion of angiotensin I to angiotensin II (dec angiotensin II and aldosterone, inc. renin and angiotensin I) + inc. bradykinin (responsiblefor coughing side effect) Angiotensin II receptor blockers (ARBS) block action of angiotensin II and AT1 receptors (inc. renin AT1 and AT2) aldosterone antagonists: compete with aldosterone in distal tubule (inc. renin, angiotensin I and II, and aldosterone)

HIV fusion and entry into cell

CD4 and CCR5 (chemokine receptor) are bound by HIV viral outer protein gp120 after bindings, HIV enters cell by fusion with cell membrane if cells do not express CCR5 protein on membrane, HIV is unable to enter cell

Study Bias

Confounding: part of the exposure-disease relationship can be explained by another variable Lead-time bias: apparent prolongation of survival in patients who were diagnosed earlier Recall bias: inaccurate patient recall of past exposure Observer bias: investigator's decision affected by prior knowledge of exposure status

Renal changes and associations

Diabetic nephrosclerosis --> glomerular sclerosis and hyalinosis Malignancy --> epithelial dysplasia long-standing HTN --> hyperplastic arteriolar changes Hemorrhage, low-flow states (MI), systemic vasodilation (sepsis) --> ischemic tubular necrosis (assoc. w. azotemia, fluid overload, electrolyte disturbances) outlet obstruction and hydronephrosis --> parenchymal pressure atrophy

Hemolytic Uremic Syndrome

Etiology: E. Coli O157LH7, Shigella (shiga-like toxin) typically has antecedent (bloody diarrheal illness), hemolytic anemia w. schistocytes, thrombocytopenia, AKI

G6PD deficiency

G6PD = rate limiting enzyme of pentose phosphate pathway that generates NADPH and ribose-5-phosphate - RBCs need NADPH to maintain glutathione - without --> RBCs more susceptible to oxidative stress

RAS gene family

GTP binding protein (signal transducer) point mutation --> carcinomas, melanoma, lymphoma

Interleukin-2

Helper T cell proliferation and differentiation Monocyte and NK cell activation T cell growth and INF gamma secretion B cell stimulation of division *inc. activity of T cells and NK cells responsible for IL-2's anti-cancer effect on metastatic melanoma and renal cell carcinoma

HHV-8

Karposi sarcoma

Aspirin

NSAID that irreversibly inhibits COX-1 and COX-2 via acetylation

Alcohol

SCC of oropharynx and upper esophagus, hepatocellular carcinoma

Arsenic

SCC of skin, lung cancer, angiosarcoma of liver

High risk HPV

SCC of vulva, vagina, anus, cervix; adenocarcinoma of cervix

Immunosuppression

Sirolimus: targets mTOR; leads to interruption of interleukin-2 signal transduction Bortezomib: inhibits 26S proteasome (used in multiple myeloma; prevents degradation of pro-apoptotic factors) Prednisone: bind with cytoplasmic receptors to dec. production of inflammatory cytokines and adhesion proteins Rituximab: chimeric antibody directed against CD20 depletes B cells Mycophenolate: inhibits de novo purine synthesis; reduces B cell and T cell proliferation

Antidiuretic Hormone (ADH/Vasopressin)

acts on medullary segment of collecting duct to increase urea and water reabsorption; allows for production of maximally concentrated urine

Hepcidin

acute phase reactant synthesized by *liver* that is the central regulator of *iron* hemostasis - interacts with transmembrane protein *ferroportin*

HTLV-1

adult T-cell leukemia/lymphoma

Vinyl chloride

angiosarcoma of liver

Parvovirus

attaches to human erythroid cells vial erythrocyte P antigen nonenveloped single-stranded DNA virus can cause aplastic crisis in sickle cell patients

Dermatomyositis

autoimmune disease with proximal muscle weakness and skin findings - heliotrope rash - Grotton's papules (raised erythematous plaques over joints and bony prominences of hands) muscle biopsy shows mononuclear perimysial infiltrates, perifasicular atrophy, pathy necrosis can occur alone or as a paraneoplastic syndrome - ovarian - lung - colorectal - NHL

Non-ionizing (UVA/UVB rays)

basal cell carcinoma, squamous cell carcinoma, melanoma of the skin *results in formation of pyrimidine dimers

Benign vs. Malignant LAD

benign = polyclonal proliferation of lymphocytes malignancy = monoclonal lymphocytic proliferation

Tumor lysis syndrome

can develop during chemo for cancers with rapid cell turnover, substantial tumor burden hyperuricemia hyperkalemia hyperphosphatemia hypocalcemia can be treated with rasburicase (converts uric acid to more soluble allantoin) or allopurinol (prevents formation of uric acid during cell lysis)

Diuretic site of action

carbonic anhydrase inhibitors (acetazolamide): proximal tubule osmotic diuretics (mannitol): descending loop of Henl loop diuretics (furosemide): thick ascending loop of Henle - target Na/K/Cl cotransporter thiazide diuretics (HCT): distal convoluted tubule potassium sparing diuretics: collecting duct - sodium channel blockers (amiloride) - aldosterone receptor antagonists (spironolactone) *reduce secretion of K and H by collecting tubule

Cigarette smoke

carcinoma of oropharynx, esophagus, lung, kidney, bladder, pancreas

Primary hemachromatosis

caused by mutation affecting HFE protein (normally interacts with transferrin to complex and act as a sensor of iron stores) mutation causes hepatocytes to detect falsely detect low iron levels and increases iron accumulation by: 1. enterocytes increase expression of DMT1 and increase iron absorption 2. hepatocytes decrease hepcidin synthesis and increase ferroportin expression on enterocytes classic triad: micronodular cirrhosis, diabetes, skin pigmentation inc. risk of HCC, CHF, and testicular atrophy

CD14

cell surface marker of monocyte-macrophage cell lineage marker in caseating granulomas

Cyanide poisoning

cyanide binds ferric iron with high affinity and inhibits cytochrome c oxidase in mitochondria --> inhibits ETC and results in severe lactic acidosis presentation: *reddish skin discoloration*, headache, tachycardia labs: lactic acidosis, narrowing of venous-arterial PO2 gradient treatment: inhaled amyl nitrate --> high affinity for cyanide and sequesters in blood

CCND1 (cyclin D1)

cyclin t(11;14) involving IgH --> mantle cell lymphoma

CDK4

cyclin-dependent kinase amplification --> melanoma

Acute Intermittent Porphyria

disorder caused by *porphobilinogen deaminase deficiency* presents acutely with GI and neurological symptoms and reddish urine that darkens on exposure to light treatment: IV heme administration and carbohydrate loading

PD-1 on T cells

down-regulates immune response against T cells by inhibiting cytotoxic T cells monoclonal antibodies blocking PD-1 prevent T cell inhibition and promote apoptosis of tumor cells

Superficial Inguinal Lymph Nodes

drain most cutaneous lymph from umbilicus down including external external genitalia and anus below dentate line *exceptions* - glans penis and skin of posterior calf (going to popliteal nodes) drain into deep inguinal nodes

Angiogenesis

driven by 1. VEGF: increases endothelial cell motility and proliferation 2. FGF-1: play important role in embryogenesis (stimulating angioblast production), also hematopoiesis and wound repair (recruiting macrophages, fibroblasts, and endothelial cells to damaged tissues laminin in basememt membranes may post a physical barrier to sprouting of new blood vessels

ERBB2 [HER2/neu]

epidermal growth factor receptor amplification --> breast carcinoma

Factor VII deficiency

failure of PT to correct with vitamin K supplementation often due to underlying liver disease Factor VII has the shortest half-life of all the coagulation factors

Resolution of hematoma

heme oxygenase degrades heme into biliverdin (green color), carbon monoxide, and ferrous iron

HBV & HCV

hepatocellular carcinoma

Aflatoxins

hepatocellular carcinoma *from aspergillus

EBV

herpesvirus with envelope glycoprotein gp350 that binds to CD21 on B cells associated with Burkitt lymphoma and nasopharyngeal carcinoma

blood:gas partition

high blood:gas partition coefficient = higher solubility

Proteasome inhibitors

i.e. Bortezomib (boronic acid-containing dipeptide) induce apoptosis of malignant plasma cells in treatment of multiple myeloma

Isotope switching for B cells

in bone marrow: primary immune response that only produces IgM Isotope switching occurs in germinal centers of lymph nodes - requires interaction of CD40 on B cells with CD154 expressed by activated T cells

Multiple Myeloma

inc. osteoclastic activity leads to inc. serum calcium, dec. PTH production - dec. renal calcium reabsorption = hypercalcuria - hypercalcemia + light chain cast nephropathy --> progressive renal failure --> dec. 1,25 dihydroxyvitamin D synthesis

Fibrinolytics (tPa)

increase clot lysis by increasing the formation of plasmin from plasminogen can cause reperfeusion arrythmias on arterial re-opening

Nitrate Poisoning

induces conversion of heme iron to oxidized ferric state ---> *methemoglobin* - unable to bind oxygen and left shift of oxygen-dissociation curve partial pressure of oxygen in blood is unchanged causes dusky discoloration of skin; induces functional anemia

Raltegravir

integrase inhibitor that disrupts ability of double-stranded HIV DNA to integrate into host-cell chromosomes

Alkylating agents

leukemia/lymphoma *side effect of chemo

Nickel, chromium, beryllium, silica

lung carcinoma

Asbestos

lung carcinoma and mesothelioma

Cytokeratin

make up the cytoskeleton of almost all epithelial cells immunohistochemical marker for epithelial-derived tumors

Disseminated Intravascular Coagulation (DIC)

massive, widespread activation of coagulation disease caused by sepsis, malignancy, or trauma will have bleeding, petechiae, bruising

MAC

minimal alveolar concentration: dose causing 50% of patients to become unresponsive to painful stimuli (ED50) [inversely proportional to potency]

Cytochrome C

mitochondrial enzyme that activates caspases indirectly brings about cell death through intrinsic pathway apoptosis

Tratuzumab

monoclonal antibody used in patients with HER2+ breast cancer binds to extracellular domain of HER2 and prevents activation of transmembrane *tyrosine kinase*

EBV

nasopharyngeal carcinoma, Burkitt lymphoma, CNS lymphoma in AIDS

RET

neural growth factor receptor point mutation --> MEN2A, MEN2B, sporadic medullary carcinoma of the thyroid

P50

partial pressure of oxygen at which hemoglobin is 50% saturated high-oxygen-affinity hemoglobins have reduced ability to release oxygen within peripheral tissues --> renal hypoxia --> inc. EPO --> compensatory erythrocytosis

PDGF

platelet derived growth factor overexpression/autocrine loop --> Astrocytoma

Primary hyperaldosteronism (Conn's syndrome)

presenting signs: HTN, hypokalemia, metabolic alkalosis, dec. plasma renin treated with aldosterone antagonist: spironolactone, eplerenone - most common side effect: gynecomastia

Carbon Monoxide Poisoning

presents with nonspecific findings (headache, dizziness, etc.) CO binds to heme with much higher affinity than oxygen ---> carboxyhempglobin - impedes oxygen delivery to tissues tx: administration of high-flow or hyperbaric oxygen therapy (hastens dissociation)

KRAS

proto-oncogene that encodes GTP-binding protein involved in regulating cell division bia transduction of extracellular signals (like EGFR) mutations are found in colon cancer activating mutations cause constitutive downstream signaling --> increased cell proliferation and growth that is *resistant to anti-EGFR therapy (cetuximab, panitumumab)*

Blood supply to ureter

proximal ureter: renal artery middle ureter: variable and anastomotic from common iliac, internal iliac, superior vesical distal ureter: superior vesical artery

Pyruvate Kinase Deficiency

pyruvate kinase = conversion enzyme that creates pyruvate and generates ATP; can also stimulate glycolysis deficiency results in insufficient ATP production and disrupts concentration gradient in RBCs - water and potassium loss - echinocyte formation - hemolysis red pulp in spleen will undergo hyperplasia and result in splenomegaly

Pure red cell aplasia

rare form of marrow failure chcracterized by *severe hypoplasia of marrow erythroid elements in the setting of normal granulopoiesis and thrombopoiesis* pathogenesis: inhibition of erythropoietic precursors and progenitors by IgG autoantibodies or cytotoxic T lymphocytes associated with thymomas and lymphocytic leukemias can result from parvovirus B19 virus (detected by anti-B19 IgM antibodies)

Vomiting

reflex activated by humoral or neuronal stimuli area postrema: in 4th ventricle, with chemoreceptor trigger zone nucleus tractus solitarius in medulla receives information from area postrema, GI tract (via vagus nerve), vestibular system, and CNS 5 major receptors involved - M1 muscarinic - D2 dopaminergic - H1 histaminic - 5-HT3 serotonergic - neruokinin 1 (NK1)

Preventing catheter-induced UTI

remove catheter promptly when no longer indicated

Dysplasia

reversible process that does not involve full thickness of epithelium; does not penetrate basement membrane

Nucleolus

round, dense, *basophilic* body that is within nucleous primary site of *ribosomal RNA* transcription by RNA polymerase I

Celecoxib

selective COX2 inhibitor potent anti-inflammatory effects without side effects of bleedings and ulceration - do not impair platelet function

Gardos channel blockers

sickle cell anemia treatment hinders the efflux of potassium and water from the cell --> prevents dehydration of erythrocytes and reduced polymerization of HbS

Ringed sideroblast

sideroblastic anemia due to ALA synthase deficiency, requires B6 as a cofactor

KIT

stem cell growth factor receptor point mutation --> gastrointestinal stromal tumor

Renal Ammoniagenesis

stimulated by acidosis; metabolism of glutamine to glutamate, generating ammonium excreted in urine and bicarb absorbed in blood *process responsible for renal acid excretion in chronic acidotic states

Nitrosamines

stomach carcinoma *found in smoked foods

Henoch-Schönlein Purpura

systemic leukocytoclastic vasculitis caused by IgA immune complex deposition will have palpable purpura, abdominal pain, arthralgias, acute glomerulonephritis

N-MYC

transcription factor amplification --> neuroblastoma

L-MYC

transcription factor amplification --> small cell lung carcinoma

c-MYC

transcription factor t(8;14) involving IgH --> Burkitt lymphoma

ABL

tyrosine kinase (signal transducer) t(9;22) with BCR --> CML and some types of ALL *philadelphia chromosome

Renal Artery Stenosis

unilateral will present with atrophy of affected side and hypertrophy of contralateral side consider in older men (with risk factors for atherosclerosis) and rarely in young women (due to fibromuscular dystrophy)

Naphthylamine

urothelial carcinoma of bladder

Western blotting

used to detect protein from a sample 1. target proteins separated by electrophoresis 2. separated proteins probed with antibody 3. membrane washed and treated with marked antibody similar to ELISA but in ELISA, patient serum tested directly

Rasburicase

used to prevent tumor lysis syndrome recombinant urate oxidase, converts uric acid to allatoin which is soluble and can be excreted in urine

Kawasaki Disease

vasculitis in medium arteries that classically affects young children high fever, conjunctivitis, cervical LAD, periungual desquamation, strawberry tonge

Renal Blood Flow

volume of blood flowing through kidney per unit time; dependent on pressure difference between renal artery and renal vein + resistance in renal vasculature RPF = PAH clearance = (urine[PAH] x urine flow rate])/plasma [PAH] RBF = PAH clearance/(1-hematocrit)

positive germ tube test

yeasts and pseudohyphae on light microscopy; diagnostic of Candida albicans infection

Metalloproteinases

zinc-containing enzymes that degrade components of extracellular matrix and basement membrane (laminin and collagen IV and VII) facilitate basement membrane penetration