Things to just fucking memorize Flashcards by Kelly Finnegan

Q

Functions of a1-receptors

A

Increase in vascular smooth muscle contraction
Increase in pupillary dilator muscle contraction
Increase intestinal and bladder sphincter muscle contraction

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Q

G-protein class of a1 receptors

A

q

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Q

Functions of a2 receptors

A

Decrease in sympathetic outflow
Decrease insulin release
Decrease in lipolysis 
Increase platelet aggregation
Decrease aqueous humor

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Q

G-protein class of a2 receptor

A

i

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Q

Functions of B1 receptors

A

Increase heart rate
Increase contractility
Increase RENIN release
Increase lipolysis

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Q

G-protein class of B1

A

s

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Q

Functions of B2 receptors

A

Vasodilation
Bronchodilation
Increase in lipolysis 
Increase insulin release 
Decrease in uterine tone
Increase aqueous humor production

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Q

G-protein class of B2

A

s

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Q

Functions of M1 receptors

A

CNS, enteric nervous system

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Q

G-protein class of M1

A

q

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Q

Functions of M2 receptors

A

Decrease heart rate and contractility of atria

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Q

G-protein class of M2

A

i

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Q

Function of M3 receptor

A

Increase exocrine glad secretions
Increase gut peristlsis
Increase bladder contraction
Ciliary muscle contraction

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Q

G-protein class of M3 receptor

A

q

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Q

Functions of D1 receptors

A

Relaxes renal vascular smooth muscle

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Q

G-protein class of D1

A

s

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Q

Functions of D2 receptors

A

Modulates transmitter release, especially the brain

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Q

G-protein class of D2

A

i

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Q

Functions of H1 receptors

A

Increase nasal and bronchial mucus production
Increase vascular permeability
Contraction of bronchioles
Pruritus 
Pain

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Q

G-protein class of H1

A

q

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Q

Functions of H2 receptors

A

Increase gastric acid secretion

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Q

G-protein class of H2

A

s

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Q

Function of V1 receptors

A

Increase vascular smooth muscle contraction

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Q

G-protein class of V1

A

q

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Function of V2 receptors

Increase water permeability and reabsorption in collecting tubules of kidney

G-protein class of V2

s

G-protein class associated with cAMP

Gs | Gi (inhibitory of Adenylyl cyclase)

G-protein class associated with increased [Ca2+] in heart

Gs | Gi (inhibitory of Adenylyl cyclase)

G-protein class associated with Increased [Ca2+] in smooth muscle contraction

Gq

Effect and applications of Albuterol, salmeterol

B2>B1 Albuterol for acute asthma; salmeterol for long-term asthma or COPD control

Effect and applications of Dobtamine

B1>B2, a Heart failure,(inotropic > chronotropic) Cardiac stress testing

Effect and applications of Dopamine

D1 = D2 > B > a Unstable bradycardia, HF, shock, Inotropic and chronotropic a effects predominate at high doses

Effect and applications of Epinephrine

B > a Analphylaxis, asthma, open-angle glaucoma a-effects predominate at high doses Significantly stronger effect at B2-receptor than norepinephrine

Effect and applications of Isoproterenol

B1 = B2 Electrophysiologic evaluation of tachyarrythmias. Can worsen ischemia.

Effect and applications of Norepinephrine

a1 > a2 > B1 Hypotension (but decrease renal perfusion) Significantly weaker effect at B2-receptor than epinephrine

Effect and applications of Phenylephrine

a1 > a2 Hypotension (vasoconstrictor) Ocular procedures Rhinitis

Effect and applications of Amphetamine

Indirect general agonist, reuptake, inhibitor, also releases stored catecholamines Used in narcolepsy, obesity, ADHD

Effect and applications of Cocaine

Indirect general agonist, reuptake inhibitor Causes vasoconstriction and local anesthesia. Never give Beta-blockers if cocaine intoxication is suspected (can lead to unopposed a1 activation and extreme hypertension)

Effect and applications of Ephedrine

Indirect general agonist, releases stored catecholamines Used in: Nasal decongestion, urinary incontinence, hypotension

IL-1

Secreted by Macrophages Also called osteoclast-activated factor. Causes fever, acute inflammation. Activates endothelium to express adhesion molecules. Induces chemokine secretion to recruit WBCs.

IL-2

Stimulated by All T-Cells Stimulates growth of helper, cytotoxic and regulatory T cells, and NK cells

IL-3

Secreted by All T-Cells Supports growth and differentiation of bone marrow stem cells. Functions like GM-CSF

IL-4

Secreted from Th2 Cells Induces differentiation into Th2 cells. Promotes growth of B cells. Enhances class switching to IgE and IgG

IL-5

Secreted from Th2 Cells Promotes differentiation of B cells. Enhances class switching to IgA. Stimulates growth and differentiation of eosinophils

IL-6

Secreted by Macrophages Causes fever and stimulates production of acute-phase proteins

IL-8

Secreted by Macrophages Major chemotactic factor for neutrophils

IL-10

Secreted from Th2 cells Modulates inflammatory response. Decreases expression of MHC class II and Th1 cytokines. Inhibits activated macrophages and dendritic cells. Also secreted by regulatory T cells

IL-12

Secreted by Macrophages Induces differentiation of T cells into Th1 cells. Activates NK cells

Interferon-gamma

Secreted from Th1 cells Secreted by NK cells in response to IL-12 from macrophages; stimulates macrophages to kill phagocytosed pathogens. Also activates NK cells to kill virus-infected cells. Increases MHC expression and presentation by all cells.

TNF-a

Secreted by macrophages Mediates septic shock. Activates endothelium. Causes WBC recruitment, vascular leak. Causes cachexia in malignancy

What cytokines are secreted by Macrophages?

``` IL-1 IL-6 IL-8 IL-12 TNF-a ```

What cytokines are secreted by All T-Cells?

IL-2 | IL-3

What cytokines are secreted from Th1 cells?

Interferon-gamma

What cytokines are secreted from Th2 cells?

IL-4 IL-5 IL-10

Whats a helpful pneumonic for remembering the actions of IL-1 through IL-6?

Hot T-Bone stEAK ``` IL-1: Fever IL-2: stimulated T-cells IL-3: stimulates Bone marrow IL-4: stimulates IgE production IL-5: stimulates IgA production IL-6: stimulates aKute-phase protein production ```

What are the Helper T cells?

Th1 and Th2

What do Th1 cells do?

Activate macropahges and cytotoxic T cells

What activates Th1 cells?

INF-y and IL-12

What inhibits Th1 cells?

IL-4 and IL-10 (from Th2 cells)

What do Th2 cells do?

Recruits eosinophils for parasite defense and promotes IgE production by B cells

What activates Th2 cells?

Activated by IL-4

What inhibits Th2 cells

IFN-y (from Th1 cells)

HLA subtypes associated with disease: | A3

Hemochromatosis

HLA subtypes associated with disease: | B27

"PAIR" Psoriatic arthritis, Anklosing spondylitis, arthritis of of Inflammatory bowel disease, Reactive arthritis

HLA subtypes associated with disease: | DQ2/DQ8

Celiac disease

HLA subtypes associated with disease: | DR2

MS hay fever SLE Goodpasture

HLA subtypes associated with disease: | DR3

Diabetes mellitus type 1, SLE, Graves disese, Hashimoto thyroiditis

HLA subtypes associated with disease: | DR4

Rheumatoid arthritis, DM1

HLA subtypes associated with disease: | DR5

Pernicious anemia >> Vit B12 deficiency Hashimoto thyroiditis

Bacterial infections associated with decreased T-cells

Sepsis

Bacterial infection associated with decreased B cells

``` Encapsulated: Step. pneumo H. flu N. meningitidis E. coli Salmonella Klebsiella pneumoniae Group B strep ```

Bacterial infections associated with decreased granulocytes

``` Staph Burkholderia cepacia Pseudomonas Serratia Nocardia ```

Bacterial infections associated with decreased complement

Encapsulated species with early component deficiences Neisseria with late component (MAC) deficiences

Viral infections associated with decreased T cells

``` CMV EBV JCV VZV Chronic infection with respiratory/GI viruses ```

Viral infections associated with decreased B cells

Enteroviral encephalitis | Poliovirus

Fungal/parasitic infections assoicated with decreased T cells

Candida (local) | PCP

Fungal/parasitic infection associated with decreased B cells

GI giardiasis (no IgA)

Fungal/parasitic infection associated with decreased granulocytes

Candida (systemic) | Aspergillus

What structures transverse the Cribiform plate?

CN I olfactory bulbs

What structures transverse the Optic canal?

CN II, opthalmic artery, central retinal vein

What structures transverse the Superior orbital fissure?

CNII, IV, V(1), VI, opthalmic vein, sympathetic fibers

What structures transverse the Foramen Rotundum?

CN V(2) (Maxillary)

What structures transverse the Foramen Ovale?

CN V(3) (Mandibular)

What structures transverse the Foramen Spinosum

Middle meningeal artery and vein

What structures transverse the Internal Acoustic Meatus

CN VII, VIII

What structures traverse the Jugular foramen?

CN IX, X, XI, jugular vein

What structures traverse the Hypoglassal canal?

CN XII

What structures traverse the Foramen Magnum?

Spinal roots of CN XI, brain stem, vertebral arteries

Enzyme deficiency in Sideroblastic anemia

∂-aminolevulinic acid synthase Glycine + succinyl CoA >>> ∂-aminolevulinic acid NEEDS Vit B6!

Enzyme deficiency in Lead poisoning

∂- aminolevulinic acid dehydrogenase: ∂-aminolevuliic acid >>> Porphobilinogen Ferrochelatase: Protoporphyrin >>> Heme

Enzyme deficiency in Acute intermittent porphyria

Porphobilinogen deaminase | Porphobilinogen >>> Hydroxymethylbilane

Enzyme deficiency in Porphyria cutanea tarda

Uroporphyrinogen decarboxylase | Uroporphyrinogen III >>> Coproporphyrinogen III

Bernard Soulier syndrome

Defect in platelet plug formation | Decrease in GpIb (platelet-to-vWF adhesion)

Glanzmann thrombocytopenia

Defect in platelet plug formation | Decrease in GpIIb/IIIa (platelet aggregation)

Immune thrombocytopenia

Anti-GpIIb/IIIa antibodies >> splenic macrophage consumption of platelet-antibody complex

Thrombotic thrombocytopenic purpura

Inhibition or deficiency of ADAMTS13 >>> decrease degradation of vWF multimers Schistocytes seen

von Willebrand disease

Intrinsic pathway coagulation defect Increase PTT Tx with desmopressin, which releases vWF stored in endothelium

Vitamin K acts as cofactor for...

factors: II, VII, IX, X Protein C, S

Protein C >> Protein S >> cleaves...

Va, VIIIa

Plasminogin >> (tPA) >> Plasmin>>> does what?

Fibrinolysis: Cleavage of fibrin mesh Destruction of coagulation factors

Translocation with Burkitt lymphoma

8:14 | c-myc activation

Translocation with CML

9:22 (Philadelphia) | BCR-ABL, which overexpresses tyrosine kinase >> cell division

Translocation with Mantle Cell lymphoma

11:14 | Cyclin D1 activation

Translocation with Follicular lymphoma

14:18 | BCL-2

Translocation in APL

15:17 | responds to all-trans retinoic acid

Mutation associated with Chronic myeloproliferative disorders

JAK2 A non-receptor kinase protein. Leads to persistant activation of signal transducers and activators of transcription (STAT) proteins

MOA for MTX, 5-FU

Decrease thymidine synthesis

MOA for 6-MP

Decrease de novo purine synthesis

MOA for Hydroxyurea

Inhibits ribonucleotide reductase

MOA for Cisplatin/Alkylating agents

Cross linking DNA

MOA for Belomycin

DNA strand breakage

MOA for Dactinomycin, doxorubicin

DNA intercalators

MOA for Etoposide

Inhibits topoisomerase II

MOA for Irinotecan

Inhibits topoisomerase I

MOA for Vinca alkaloids

Inhibit microtubule formation

MOA for Paclitaxel

Inhibits microtubule disassembly

CYP450 Inhibitors

``` Acetaminophen, NSAIDs Antibiotics/Antifungals Trimethoprin-sulfamethoxazole Amiodarone Cimetidine Cranberry juice, Ginkgo biloba, Vit E Omeprazole Thyroid hormone SSRIs (fluoxetine) ```

CYP450 Inducers

``` Carbamazepine Ginseng Green veggies Oral contraceptives Phenobarbital Phenytoin Rifampin St Johns Wart ```

RAS oncogene

1-hit GAIN of function GTP-binding protein Cholangiocarcinoma Pancreatic adenocarcinoma

MYC oncogene

1-hit GAIN of function Transcription factor Burkitt lymphoma

BRCA 1/2 oncogene

2-hit LOSS of function DNA repair genes Breast and ovarian cancer

APC/ß catenin oncogene

2-hit LOSS of function Wnt signaling pathway Colon, gastric and pancreatic cancer Familial adenomatous polyposis

ERBB1 (EGFR) oncogene

1-hit GAIN of function Receptor tyrosine kinase Lung adenocarcinoma

TP53 oncogene

2-hit LOSS of function Genomic stability Most cancers Li-Fraumeni syndrome

ERBB2 (HER2) oncogene

1-hit GAIN of function Receptor tyrosine kinase Breast cancer

RB oncogene

2-hit LOSS of function G1/S transition inhibitor Retinoblastoma Osteosarcoma

ABL oncogene

1-hit GAIN of function Nonreceptor tyrosine kinase CML

BRAF oncogene

1-hit GAIN of function Ras signal transduction Hairy cell leukemia Melanoma

VHL oncogene

2-hit LOSS of function Ubiquinitin ligase component Renal cell carcinoma Von Hippel-Lindau syndrome

WT1 oncogene

2-hit LOSS of function Urogenital differentiation Wilms tumor

What does Gastrin do, and where does it come from?

Secreted from G cells in gastric antrum, duodenum Increases gastric acid secretion

What does Somatostatin do and where does it come from?

Secreted from D cells from the pancreatic islets and in gut mucosa Decreases secretion of most GI hormones

What does Cholecystokinin do and where does it come from?

Secreted from I cells in small intestine Increases pancreatic enzyme and HCO3- secretion

What is Secretin and where does it come from?

Secreted from S cells in the small intestine Increases pancreatic HCO3- secretion Decreases Gastric acid secretion

What is GIP and where does it come from?

K cells in small intesting Increases insulin release Decreases Gastric acid secretion

What is motilin and what does it do?

M cells in small intestine Increases GI motility

Drugs that can cause Steven Johnson Syndrome

Anti-epileptic drugs (especially lamotrigine) Allopurinol Sulfa drugs Penicillin

Drugs that can cause Drug-Induced Lupus

SHIPP-E Sulfa drugs, Hydralazine, Isoniazid, Procainamide, Phenytoin, Etanercept

P450 Inducers

``` Chronic alcohol use St Johns Wart Phenytoin Phenobarbital Nevirapine Rifampin Griseofulvin Carbamazepine ``` "Chronic alcoholics STeal PHEN-PHEN and NEver Refuse GReasy CARBs"

P450 Inhibitors

``` Acute Alcohol Abuse Ritonaer Amiodarone Cimetidine Ketoconazole Sulfonamides Isoniazid (INH) Grapefruit juice Quinidine Macrolides (except azithromcin) ``` "AAA RACKS IN GQ Magazine"

P450 Substrates

Anti-epileptics Theophylline Warfarin OCPs "Always Think When Outdoors"

List of Sulfa Drugs

``` Probenecid Furosemide Acetazolamde Celecoxib Thiazides Sulfonamide antibiotics Sulfasalazine Sulfonyureas ``` "Popular FACTSSS"

Live attenuated virus vaccines:

Induce humoral and cell-mediated immunity. Rarely revert back to virulence. No booster needed. Dangerous for immunocompromised patients. ``` Smallpox Yellow fever Rotavirus Chickenpox Sabin polio MMR Influenza (intranasal) ```

Killed viral vaccines:

Induce ONLY humoral immunity. Stable, cannot revert. Rabis Influenza (injected) Salk Polio HAV

Subunit viral vaccines:

HBV (antigen = HBsAg) | HPV

Encapsulated bacteria vaccine

Contain polysaccharide capsule antigens that are conjugated to a carrier protein. (Polysaccharide antigen alone cannot be presented to T-cells). T-cell activation and subsequent class-switching. Pneumococcal (two types: one is conjugated, one isn't) H. flu type B Meningococcal

Urease-positive organisms

``` Cryptococcus H. pylori Proteus Ureaplasma Nocardia Klebsiella S. epidermidis S. saprophyticus ```

Obligate intracellular bugs

Rickettsia Chlamydia Coxiella Rely on host ATP

Facultative intracellular bugs

``` Salmonella Neisseria Brucella Mycobacteria Listeria Francisella Legionella Yersinia pestis ```

Encapsulated bacteria

``` Streptococcus pneumoniae H. flu type B Neisseria E. coli Salmonella Klebsiella Group B strep ``` Are opsonized and then cleared by spleen. Increased infection for aslpenics

Catalase-positive organisms

``` Nocardia Pseudomonas Listeria Aspergillus Candida E. coli Staph Serratia ```

Protein A virulence factor: | What bug uses it, and how does it work?

Expressed by S. aureus Binds Fc region of IgG. Prevents opsonization and phagocytosis

IgA protease virulence factor: | What bugs use it, and how does it work?

Secreted by S. penumoniae, H. flu type B and Neisseria Cleaves IgA in order to colonize respiratory mucosa

M protein virulence factor: | What bugs use it, and how does it work?

Expressed by group A Strep Helps prevent phagocytosis. Shares similar epitopes to human cellular protein (molecular mimicry)- underlies the autoimmune response of rheumatic fever

Exotoxin of Corynebacterium diphteriae

Diphtheria toxin Inactivates EF-2 Pharyngitis with psudeomembranes in throat and severe lymphadopathy (bull neck)

Exotoxin of Pseudomonas aeruginosa

Exotoxin A Inactivates EF-2 Causes host cell death

Exotoxin of Shigella spp.

Shiga toxin Inactivates 60S ribosome by removing adenosine from rRNA Causes GI mucosal damage, causing dysentery. Also enhances cytokine release, causing hemolytic-uremic syndrome

Exotoxin of E. Coli (EHEC)

Shiga-like toxin Inactivate 60S ribosome by removing adenine from rRNA Enhances cytokine release, causing HUS.

Exotoxin of Bacillus anthracis

Edema toxin Mimics the adenylate cyclase enzyme (increase cAMP) Likely responsible for characteristic edematous boarders of black eschar in cutaneous anthrax

Exotoxin of Vibrio cholerae

Cholera toxin Overactivates adenylate cylcase (increase cAMP) by permanently activating Gs, leading to and increase in Cl- secretion in gut and H2O efflux Voluminous rice-water diarrhea

Exotoxin in Bordetella pertussis

Pertussis toxin Overactivates adenylate cyclase (increase cAMP) by disabling Gi, impairing phagocytosis to permit survival of microbe Whooping cough

Exotoxin of Clostridium tetani

Tetanospamin Proteases that cleave SNARE. Prevents release of GABA and glycine from Renshaw cells in spinal cord Spasticity, clonus, lockjaw

Exotoxin of Clostridium botulinum

Botulinum toxin Protease that cleave SNARE. Prevents release of ACh at NM junctions Flaccid paralysis

Exotoxin of Clostridium perfringens

Alpha toxin Phospoliase that degrades tissue and cell membranes Degradation of phopholipids leading to "gas gangrene" and hemolysis (double zone of hemolysis on blood agar)

Exotoxin of Streptococcus pyogens - Cell membrane variety

Stretptolysin O Protein that degrades cell membrane Lyses RBCs; contributes to B-hemolysis. Host antibodies against toxin (ASO) are sued to diagnose rheumatic fever

Exotoxin in Staph. aureus

Toxic Shock Syndrome Toxin (TSST-1) Binds to MCH II and TCR outside of antigen binding site to cause overwhelming release of IL-1, IL-2, IFN-y, and TNF-a, leading to shock TSS = fever, rash, shock. Other toxins can cause scalded skin syndrome (exfoliative toxin) and food poisoning (enterotoxin)

Exotoxin in Strep. pyogenes - shock variety

Exotoxin A Binds to MCH II and TCR outside of antigen binding site to cause overwhelming release of IL-1, IL-2, IFN-y, and TNF-a, leading to shock TSS= fever, rash, shock

Affects fo Endotoxin

Use "ENDOTOXIN" to remember the main points) ``` Edema Nitric oxide release (hypotension) DIC/Death Outer membrane of most gram-negative is where its found TNF-a O-antigen eXtremely heat stable IL-1 Neutrophil chemotaxis ```

NPH insulin

Long acting, twice daily dosing 18 hours

Glargine insuline

Long acting, once daily 24 hour duration

Determir insulin

Long acting, once daily 24 hour duration

Regular insulin

Short acting Peaks 2-4 hours Best for IV use in diabetic ketoacidosis

Lispro insulin

Post-prandial | Peak 45-75 min

Aspart insulin

Post-prandial | Peak 45-75 min

Glulisine insulin

Post-prandial | Peak 45-75 min

Cyclosporine: Cell Target and side effects

Inhibits calcineurin Blocks T-cell activation by preventing IL-2 transcription SI: Nephrotoxicity, hypertension, hyperlipidemia, gingival hyperplasia

Tacrolimus (FK506): Cell Target and side effects

Inhibits Calcineurin; binds FK506 binding protein Blocks T-cell activation by preventing IL-2 transcription SI: Nephrotoxicity. Increased risk of diabetes and neurotoxicity. NO gingival hyperplasia

Siroliumus (Rapamycin): Cell target and side effects

mTOR inhibitor. Binds FKPB. In cytoplasm. Blocks T-cell activation and B-cell differentiation by preventing response to IL-2 SI: Anemia, thromobycopenia, leukopenia. NOT nephrotoxic (so its good for kidney transplants)

Daclizumab, Basiliximab: Cell target and SI

Monoclonal antibodies, blocks IL-2R MEMBRANE RECEPTOR inhibitor SI: Edema, hypertension, tremor

Azathioprine: Cell target and SI

Antimetabolite precursor of 6-mercaptopurine. Inhibits lymphocyte proliferation by blocking nucleotide synthesis. Blocks PRPP amidotransferase (cytoplasm) so Purine nucleotides cannot take part in DNA replication (nucleus) SI: Leukopenia, anemia, thrombocytopenia *6-MP degraded by xanthine oxidase, so toxicity is increased by allopurinol*

Glucocorticoids: Cell target and SI

Inhibit NF-kB. Suppress both B and T cell function by decreasing transcription of many cytokines. IN the NUCLEUS

Atrial natriueretic peptdie

Released from atrial myocytes in response to increased blood volume and atrial pressure. Acts via cGMP Causes vasodilation and lowers Na+ reabsorption at the renal collecting tubule Dilates afferent renal arterioles and constricts efferent arterioles, promoting diuresis

B-type (brain) natriuretic peptide

Released from Ventricular myocytes in response to increased tension. Similar physiologic action to ANP, with longer half life. BNP blood test in sued for diagnosing F

Leads with ST elevation for LAD infarct

V1-V2 V3-V4 (distal LAD) V5-V6 (LAD or LCX)

Leads with ST elevation for LCX infarct

V5-V6 (LAD or LCX) I, aVL

Leads with ST elevation for inFerior RCA infarct

II, III, aVF

The "6" nephrotic syndromes to remember

Minimal Change Disease Focal Segmental Glomerulosclerosis Membrane Nephropathy Membranoproliferative (can also be nephritic) Diabetes Mellitus System Amyloidosis

Examples of Nephritic Syndrome

``` Alport Syndrome IgA Nephropathy Post-Streptococcal Glomerulonephritis Goodpastures Diffuse Proliferative GN Wegners Churg-Staus Microscopic polyangitis ```

Minimal Change Disease

Nephrotic Syndrome Associated with Hogkins Lymphoma Idiopathic Podocytes lose foot processes due to cytokine damage Normal HE stain ONLY albumin is lost. NOT immunoglobulins Responds well to steroids

Focal Segmental Glomerulosclerosis

Idiopathic Seen in HIV, heroin use, Sickle Cell (so you know, brown people...ugh) "Progression of MCD if it doesn't respond to steroids"

Membrane Nephropathy

Idiopathic Seen in Lupus! Also Hep B, C, solid tumors, NSAID use Thick basement membrane "Spike and dome" appearance" Immune complex deposition under foot processes. Granular, sub-epithelial Antibodies to the PLA2-receptor found on podocytes

Membranoproliferative GN

Can be Nephritic OR Nephrotic Immune complex deposition Type I: Subendothelial, more often "Tram Track" appearance". Seen in Hep B, Hep C Type II: Deposition WITHIN the basement membrane. Autoantibody of C3 nephritic factor. Stabilizes C3 convertase, increasing inflammation. (Low C3, High inflammation)

Diabetic Mellitus Nephropathy

``` Non-enzymatic glycosylation Hyline arteriolosclerosis (efferent vessel) Thick vessel wall Give ACE-inhibitor! Kemmelstiel-Wilson nodules!! ```

Systemic Amyloidosis Nephropathy

Congo-red stain Apple green bifringence Kidney is most commonly affected organ in amyloidosis

Alport Syndrome

X-linked disorder of IV collagen Thinning and splitting GBM Isolated hematuria Sensory hearing loss, eye problems

Post-Streptococcal GN

M-protein virulence factor Immune complex (granular) Sub-epithelial hump Supportive tx Adults can develop Rapidly Progressive GN, creating crescents in Bowman's Space (composed for macrophages and fibren)

IgA Nephropathy

Deposits in mesangium Can progress to renal failure

Goodpastures

Antibodies to the Basement membrane (alpha3-chain of collagen type IV) Linear IgG and C3 deposition

Diffuse proliferative GN

Lupus! | Granular IF deposits

Wegeners

``` c-ANCA Affects Nose, Lung, Kidney Pauci-immune Sinus problems!! NO linear complex (not immune complexes, instead, c-ANCA) ```

Churg-Staus

``` p-ANCA Granulomatous EOSINOPHILIA ASTHMA Can involved GI tract, CV system. Commonly vasculitis affecting the epineural vessels (can see a wrist drop, for example) ``` Frequent laboratory finding: antibodies against neutrophil myeloperoxidase

Microscopic Polyangitis

p-ANCA NO eosinophilia or asthma

Anti-oncogenes (therefore inactivated in cancer)

APC BRCA1 RB TP53

Burkitt Lymphoma; associations

Adolescents or young adults "Starry sky" appearance Associated with EBC Jaw lesion = Africa Pelvis/Abdomen = Sporadic

Burkitt Lymphoma; genetics

t(8;140 | c-myc

Diffuse Large B-cell lymphoma; associations

Older adults, 20% in kids | Most common type of non-Hodgkin lymphoma in adults

Follicular lymphoma; associations

Adults Presents with "waxing and waning" lymphadenopathy. Nodular, small cells; cleaved nuclei Bcl-2 inhibits apoptosis

Follicular lymphoma; genetics

t(14;18) translocation of heavy-chain Ig (14) and BCL-2 (18)

Mantle cell lymphoma; associations

Older males CD5+

Mantle cell lymphoma; genetics

t(11;14) Translocation of cyclin D (11) and heavy-chain Ig (14)

Adult T-cell lymphoma

Adults Caused by HTLV (associated with IV drug abuse) Present with cutaneous lesions; especially affects population in Japan, West Africa and Caribbean. Lytic bone lesions, hypercalcemia

Mycosis fungiodes/Sezary

Adults Presents with skin patches/plaques (cutaneous T-cell lymphoma) Atypical CD4+ cells with "cerebriform" nuclei. May progress to Sezary syndrome (T-cell luekemia)

Multiple Myeloma; symptoms

``` CRAB: HyperCalcemia Renal involvement Anemia Bone lytic lesions/Back pain Monoclonal M protein spike ``` Associated with increased susceptibility to infection and Primary amyloidosis

Multiple Myeloma; histologic/diagnostic findings

Ig light chain in urine Rouleaux formation Numerous plasma cells with "clock face" chromatin and intracytoplasmic inclusions containing immunoglobulin Monoclonal plasma cells = "fried egg" appearance

Myelodysplastic syndromes

Stem cell disorders involving ineffective hematopoiesis Caused by de novo mutation or environmental exposure (radiation, benzene, chemotherapy) Risk of transformation to AML

Acute lymphoblastic leukemia/lymphoma (ALL); associations

``` Under 15 years old Down syndrome Peripheral blood and bone marrow have increased lymphoblasts TdT+ marker (pre-T and pre-B) CD10+ (pre-B) ``` May spread to CNS and testes

Acute lymphoblastic leukemia/lymphoma (ALL); genetics

t(12;21)

Chronic lymphoblastic leukemia | /small lymphocytic lymphoma

Older than 60 years Most common adult leukemia Often asymptomatic, progresses slowly Smudge cells seen in peripheral smear Autoimmune hemolytic anemia CD20+, CD5+ B-cell neoplasm

Hairy Cell Leukemia

Adults Mature B-cell tumor Dry tap bone marrow Stains TRAP Tx: cladribine, pentostatin

Acute myelogenous leukemia (AML); associations

Median age ~65 Auer rods Cytoplasmic inclusions Increase in circulating myeloblasts Down Syndrome Risk: exposure to alkylating chemotherapy, radiation, myeloproliferative disorders M3 AML responds to all-trans retinoic acid DIC is a common presentation

Acute Myelogenous Leukemia; genetics

t(15;17)

Chronic Myelogenous Leukemia (CML)

Peak incidence 45-85 years Myeloid stem cell proliferation; Presents with increased neutrophils, metamyelocytes, basophils, splenomegaly May transform to AML or ALL (blast crisis) Responds to imatinib

Chronic Myelogenous Leukemia (CML); genetics

Philadelphia chromosome t(9;22)

Region of the BRAIN most at risk for ischemic damage

ACA/MCA/PCA boundary areas

Region of the HEART most at risk for ischemic damage

Subendocardium (LV)

Region of the KIDNEY most at risk for ischemic damage

Straight segment of proximal tubule (medulla) | Thick ascending limb (medulla)

Region of the LIVER most at risk for ischemic damage

Area around central vein (zone III)

Region of the COLON most at risk for ischemic damage

Splenic flexure | Rectum

Paraneoplastic Syndrome: Acanthosis nigricans

Gastric adenocarcinomas and other visceral malignancies

Paraneoplastic Syndrome: Sign of Leser-Trelat (an explosion of seborrheic keratoses)

GI adenocarcinomas and other visceral malignancies

Paraneoplastic Syndrome: Hypercalcemia

PTHrP Squamous cell carcinomas of lung, head, neck Renal, bladder, breast, ovarian carcinomas In lymphoma, is by the mechanism of increased 1,25(OH2) Vitamin D3

Paraneoplastic Syndrome: Cushing Syndrome

Increase in ACTH Small cell lung cancer

Paraneoplastic Syndrome: Hyponatremia (SIADH)

Increase in ADH Small cell lung cancer

Paraneoplastic Syndrome: Polycythemia

Increase in Erythropoietin ``` Renal cell carcinom Hepatocellular carcinoma Hemangioblastoma Pheochromocytoma Leiomyoma ```

Paraneoplastic Syndrome: Pure re cell aplasia

Anemia with low reticulocytes Thymoma

Paraneoplastic Syndrome: Trousseau Syndrome

Migratory superficial thrombophlebitis Adenocarcinomas, especially pancreatic

Paraneoplastic Syndrome: Nonbacterial thromboic endocarditis

Deposition of sterile platelet thrombi on heart valves Adenocarcinomas, especially pancreatic

Paraneoplastic Syndrome: Anti-NMDA receptor encephalitis

Psychiatric disturbance, memory deficits, seizures, dyskinesias, autonomic instability, language dysfunction Ovarian teratoma

Paraneoplastic Syndrome: Opsoclonus-myoclonus ataxia ("Dancing eyes, dancing feet")

Neuroblastoma (children) Small cell lung cancer (adults"

Paraneoplastic Syndrome: Antibodies against Hu, Yo and Tr antigens in Purkinje cells

Small cell lung cancer Gynecologic and breast cancers Hodgkin lymphoma

Paraneoplastic Syndrome: Antibodies against Hu antigens in neurons

Small cell lung cancer

Paraneoplastic Syndrome: Lambert-Eaton myasthenic syndrome

Antibodies against presynaptic Ca2+ channels at NMJ Small cell lung cancer

Paraneoplastic Syndrome: Myasthenia gravis

Antibodies against postsynaptic AChR at NMJ Thymoma

Cancer caused by arsenic

Liver - angiosarcoma Lung- lung cancer Skin - SCC

Cancer caused by Aromatic amines

Bladder - Transitional cell carcinoma

Cancer caused by alkylating agents

Blood - leukemia/lymphoma

Serum tumor marker: Alkaline phosphatase

Mets to bone or liver Paget disease of one Seminoma (placental ALP)

Serum tumor marker: alpha-fetoprotein

Hepatocellular carcioma Hepatoblastoma Yolk sac (endodermal sinus) tumor Mixed germ cell tumor

Serum tumor marker: Beta-hCG

Hydatidiform moles Ghoriocarcinomas (produced by syncytiotrophoblasts of the placenta)

Serum tumor marker: CA 15-3/CA 27-29

Breast cancer

Serum tumor marker: CA 19-9

Pancreatic adenocarcinoma

Serum tumor marker: CA 125

Ovarian cancer

Serum tumor marker: Calcitonin

Medullary thyroid carcinoma

Serum tumor marker: CEA

CarcinoEmbyronic Antigen Very nonspecific, but produced by ~70% of colorectal and pancreatic cancers. Also produced by gastric, breast, and medullary thryoid carcinomas

Serum tumor marker: PSA

Prostate-specific antigen. Sooooo Prostate cancer. Can also be elevated in BPH and prostatitis

What is P-glycoprotein?

aka Multidrug resistance protein 1 (MDR1). Classically seen in adrenal cell carcinoma but also expressed by colon and liver cancer cells. Used to pump out toxins, including chemotherapeutic agents

Cardiac wall damage with LAD infarct

Anterior wall | Shared LV/RV wall

Cardiac wall damage with RCA infarct

Posterior wall | Shared LV/RV wall

Cardiac wall damage with L. Circumflex infarct

Left lateral wall

Systolic Murmurs

Aortic Stenosis Mitral/Tricuspid Regurg Mitral Valve prolapse Ventricular septal defect

Diastolic Murmurs

Aortic regurgitation | Mitral stenosis

Murmur heard in Aortic stenosis

Systolic Crescendo-decrescendo systolic ejection murmur (ejection click may be present) Loudest at heart base. Radiates to carotids Pulses weak with delayed peak Can lead to Syncope, Angina, and Dyspnea on exertion

Murmur heard in Mitral/Tricuspid Regurgitation

Systolic Holosystolic, high-pitched, "blowing" murmur Mitral: loudest at apex and radiates to axilla. Often due to ischemia heart disease Tricuspid: loudest at tricuspid area and radiates to right sternal border. Commonly caused by RV dilatation

Murmur heard in Mitral valve Prolapse

Systolic ``` Late systolic crescendo murmur with midsytolic click (due to sudden tensing of chordae tendinae). Most frequent valvular lesion. Best heard over apex Loudest just before S2 Usually benign Can predispose to infective endocarditis ```

Murmur heard in Ventricular Septal Defect

Holosystolic, harsh-sounding | Loudest at tricuspid area

Murmur heard in Aortic Regurgitation

Diastolic High-pitched "blowing" early diastolic decrescendo murmur Long diastolic murmur Hyperdynamic pulse, head-bobbing. Wide pulse pressure. Often due to aortic root dilation, biscupid aortic valve, endocarditis, rheumatic fever. Progresses to left HF

Murmur heard in Mitral Stenosis

Diastolic Follows opening snap Delayed rumbling late diastolic murmur Decreased interval between S2 and opening snap correlates with increased severity LA >> LV pressure during diastole

Result of Inspiration on cardiac exam

Increased venous return of RA | Increases intensity of right heart sounds

Result of Hand Grip on cardiac exam

Increase in afterload Increase intensity of MR, AR, VSD murmurs Decrease in hypertrophic cardiomyopathy murmurs MVP: later onset of click/murmur

Result of Valsalva manuver/Standing up on cardiac exam

Decrease preload Increase intensity of hypertrophic cardiomyopathy murmur Decrease intensity of most murmurs

Result of Rapid Squatting on cardiac exam

Increase venous return, Increase preload, Increase afterload Decrease intensity of hypertorphic cardiomyopaty murmur Increase in intensity of AS murmur

What does S3 heart sound relate to?

Associated with increased filling pressure (Mitral regurg, HF) More common in dilated ventricles Can be normal in kids and young adults

What does S4 heart sound relate to?

(Best heart at apex with pt lying on left side) Associated with ventricular noncompliance (hypertrophy). Left atrium must push against still LV wall. Always abnormal!

What artery supplies the SA and AV nodes?

The RCA

Conditions when you see an increased pulse pressure

``` Aortic Regurgitation Aortic Stiffening (isolated systolic hypertension in elderly) Sleep apnea Exercise HYPERthyroid ```

Conditions when you see a decreased pulse pressure

Aortic stenosis Cardiogenic shock Cardiac tamponade Advanced HF

You hear a systolic murmur over the right sternal border. What could it be?

Aortic stenosis Aortic valve sclerosis Flow murmur (physiologic murmur)

You hear a Diastolic murmur over the left sternal border. What could it be?

Aortic regurgitation | Pulmonic regurgitation

You hear a Systolic murmur over the left sternal border. What could it be?

Hypertrophic cardiomyopathy `

You hear a Systolic ejection murmur over the pulmonic area. What could it be?

Pulmonic stenosis

You hear a Holosystolic murmur in the tricuspid area. What could it be?

Tricuspid regurgitation | VSD

You hear a Diastolic murmur over the tricuspid area. What could it be?

Tricuspid stenosis | ASD (increased flow across tricuspid valve)

You hear a Holosystolic murmur over the mitral area. What could it be?

Mitral regurgitation

You hear a Diastolic murmur over the mitral area. What could it be?

Mitral stenosis

What is Wolff-Parkinson-White syndrome?

Most common ventricular pre-excitation syndrome Abnormal fast accessory conduction pathway from atria to ventricle (bundle of Kent) bypasses the rate-slowing AV node, so the ventricles start to partially depolarize earlier See delta wave with widened QRS complex and shortened PR interval May result in reentry circuit and supraventricular tachycardia

What is the "Aldosterone Escape" thing?!

A term that has been used to refer to two distinct phenomena involving aldosterone that are exactly opposite each other: 1. Escape from the sodium-retaining effects of excess aldosterone (or other mineralocorticoids) in primary hyperaldosteronism, manifested by volume and/or pressure natriuresis. 2. The inability of ACE inhibitor therapy to reliably suppress aldosterone release, for example, in patients with heart failure or diabetes, usually manifested by increased salt and water retention. This latter sense may rather be termed refractory hyperaldosteronism.

What the fuck is Phosphodiesterase

Any of a class of enzymes that catalyze the hydrolytic cleavage of phosphodiester bonds and are important in breaking down cyclic AMP, cyclic GMP, and nucleic acids

What the fuck are Phosphodiesterase Inhibitors and what do they do

Well, they inhibit Phosphodiesterase, thereby INCREASING cAMP ``` Effects: Impaire platelet function Help you get a boner Positive iontropy Vasodilation ```

Association to Antibodies to myeloperoxidase and proteinase-3

Involved in pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides such as microscopic polyangiitis and granulomatosis with polyangiitis

Association to B-cell activating factor (BAFF)

BAFF is a cytokine belonging to the tumor necrosis factor ligand family. Inadequate levels of BAFF will lead to immunodeficiency Excess levels cause autoimmune disease

DRESS syndrome

Rare and potentially life-threatening drug reaction typically occurring 2-8 weeks after exposure to drugs like ANTICONVULSANTS (phenytoin, carbamazepine) ALLOPURINOL, sulfaonamides and some antibiotics (minocyline, vanco). ESOSINOPHILIA Presents with fever, generalized lymphadenopathy, facial edema and skin rash

Von Recklinghausen's Disease

aka Neurfibromatosis type 1 Inherited peripheral nervous system tumor syndrome. Patients develop neurofibromas, optic nerve gliomas, Lisch nodules (pigmented nodules of the iris), and cafe au lait spots

Neurofibromatosis type 2

AD Bilateral cranial nerve VIII schwannomas and multiple meningiomas

Sturge-Weber syndrome

aka encephalotrigeminal angiomatosis Congenital neurocutaneous disorder. Cutaneous facial angiomas, leptomeningeal angiomas Skin involvement typically overlies the ophthalmic (V1) and maxillary (V2) distributions of the trigeminal nerve Skull shows "tram track" calcifiations

Tuberous Sclerosis

AD May cause kideny, liver and pacreatic cysts CNS hamartomas. Seizures

von Hippel-Lindau; Gene and Associated neoplasm

VHL gene Capillary hemangioblastomas in the retina and/or cerebellum. Congenital cysts and/or neoplasms in the kidney, liver and pancreas Increased risk for renal cell carcinoma, which can be bilateral

Lynch syndrome, Genes and Associated neoplasms

MSH2 MLH1 MSH6 PMS2 Colorectal cancer Endometrial cancer Ovarian cancer Autosomal Dominant. Caused by inactivating mutation in corresponding tumor suppressor gene (second hit leads to malignant transformation)

Familial adenomatous polyposis; Gene and Assocated neoplasms

APC Hemangioblastomas Clear cell renal cell carincoma Pheochromocytoma Autosomal Dominant. Caused by inactivating mutation in corresponding tumor suppressor gene (second hit leads to malignant transformation)

Multiple endocrine neoplasia type 1; Gene and Assoicated neoplasms

MEN 1 Parathyroid adenomas Pituitary adenomas Pancreatic adenomas Autosomal Dominant. Caused by inactivating mutation in corresponding tumor suppressor gene (second hit leads to malignant transformation)

Multiple endocrine neoplasia type 2; Gene and Associated neoplasms

RET Medullary thyroid cancer Pheochromocytoma Parathyroid hyperplasia (MEN2A) Autosomal dominant. ACTIVATING (gain-of-functions)

Li-Fraumeni Syndrome; Gene and Associated neoplasms

TP53 ``` Sarcomas Breast cancer Brain tumors Adrenocortical carcinoma Leukemia ```