Female: lung, breast, colon, pancreatic

Males: lung, prostate, colon, pancreatic

Anatomical: tumor obstructs a pivotal body part and you die of that (ex: cervical cancer obstructs ureters, die of renal failure)

Tumor mass: If the tumor gets big enough, it will take up too many of the body's nutrients 

Infection: bone marrow (anemia, WBC decereases) die of sepsis

TNM

Tumor size: <2.5cm = T1, >5cm = T3

Nodes: 0= no nodal involvement

Metastases: 0 = not present, 1 = present

Stage 1 - T1, N0, M0

80-90% 5 year survival

Stage IV - survival rates very slim

Staging

Overall health of Pt

Type of cancer

Presence/Type of receptor (some receptors can be blocked)

Availability of care

Anatomical: Breast, liver, pancreas

Pathological:

Derived from squamous cells: carcinoma

Glandular tissue: adenocarcinoma

Mesodermal tissue (bone, muscle, connective tissue): sarcoma

Hematologic: leukemia, lymphoma, etc

Germ cell cancers: different names

1. Neoplastic cell growth is poorly controlled

2. High nuclear to cytoplasmic ratio in neoplasia

3. cancer cells divide more often

4. cancer cells lose ability to fxn properly - mitosis occurs throughout cells, not just in basal layer

5. immortality - do not undergo apoptosis, telomeres are indestructable

1st degree relative doubles your risk

lifetime risk: 1/8

it is a normal gene that helps cells grow... such as in chidlren or in adult bone marrow/skin cells

if it is mutated, it becomes an oncogene

Normal genes that repair DNA errors

Loss of tumor suppressor genes in a cell increases the risk of malignant transformation

Each cell has two copies of the TSG called BRCA-I and BRCA-II, having only one copy of this increases chance of cancer.

dysplasia

pap smears

1. As we age, repair capacity decreases

2. accumulation of errors

Exception: germ cell tumors tend to show up in kids

that in addition to primary cancer treatment (surgery & radiation)

Adjuncts: chemo, hormonal treatment (for receptor-pos tumors), monoclonal antibody drugs that targets HCR2)

It is given to women to prevent/treat osteoporosis, however estrogen feeds breast cancer.

Solution? give estrogen that only stimulates bone receptors and blocks breast receptors

estrogen receptor blockers

aromatase inhibitors

chemo drugs damage all the body's cells so they must be administered in a cyclic fashion so as to kill the tumor cells but not cause organ damage

1. pt gets hammered wtih drugs over a day or two

2. wait a few weeks for normal body cells to repair

3. do it again in a few weeks to knock tumor cells down a few notches

due to several times until tumor cells are gone

1. prophylactic antibiotics for the most likely infections - staph, strep from skin, gram neg organisms from colon (e. coli, C diff)

2. Clean out colon as much as possible before surgery to reduce bacterial load

3. prep skin as much as possible before surgery to get bacteria off

cancer

tumor

malignant

neoplasia

copy errors

electromagnetic damage (UV, xrays, gamma rays)

cosmic rays

Chemicals (free radicals)

gatekeeper genes

caretaker genes

something about being a tumor suppressor gene

"guardian angel gene"

any cell can undergo malignant transformation

Toxins of some kind triggers the transformation (ionizing radiation, certain chemicals, perhaps viruses)

Transformation usually occurs relatively quickly (weeks to months)

genetic background is important in determining susceptivility

several mutations must occur in one cell before transformation occurs (oncogene is activated and tumor suppressor gene is inactivate)

normal immune surveillance fails

usually requires long periods of time to occur

cancer require multistep transformation of stem cells

most tumor cells can proliferatue only briefly (only malignant step cells are immortal and drive tumor growth)

if we can learn to control stem cells we may be able to control cancer

most cancer cells display self MHC molecules

T lymphs that are more effective against cancer cells would likely cause autoimmune disase and affect reporduction

Kaposi's sarcoma (herpes virus 8)

cervical cancer (HPV)

lymphoma (epstein barr virus)

pleomorphic

large

frequent

loss

loss

loss

surgery

chemo

radiation

immunotherapy

chromosome 17

Chromosome 13

chemo targets rapidly dividing cells - like neoplasia, but also bone marrow & hair follicles (and embryonic/fetal cells and GI endothelium)

Bone marrow suppression results in:

Anemia (fatigue, less O2 transport)

neutropenia (infections)

thrombocytopenia (hemorrhage)

it improves pt well being

improves pt functioning

***increases tolerance to additional chemo.. which leads to improved outcome ***

Human Epidermal growth factor Receptor

Represents a proto-oncogene that is + in about 1/3 of breast cancer

Mutation results in amplification of growth factor

HER-2 positivity lowers prognosis

Now trying anti-HER-2 treatment

Eukaryotes - have nucleus - protozoa and fungi

Prokaryotes - gram neg (red) - gram pos (blue)

Have cell wall

anaerobic or aerobic

cocci or bacilli(rods)

Other prokaryotes: Mycoplasma - have no cell wall, Chlamydia - intracellular reproduction, rickettsia - typhus, rocky mtn spotted fever

Non-living pathogens - viruses, prions

gram + cocci

Gram + rods/bacilli

Gram - cocci

Gram - rods/bacilli

Bacteriostatic - slows microbial growth until host immune system can gain the upper hand - for routine infections

bacteriocidal - in compromised pts, employs agents designed to kill a significant # of microbes - for very serious infections

1. Inhibit folate production - sulfa drugs, trimethoprim, bactrim

2. Inhibit cell wall symthesis (B-lactams - PENICILLIN, caphalosporins, vancomycin, bacitracin)

3. Inhibit protein synthesis - 50S or 30S inhibitors - TETRACYCLINES, aminoglycosides, marcolides (Erythromycin)

4. inhibit nucleic acid - fluoroquinolones

explosive bloody diarrhea which can be life threatening

C. DIFF

seen after antibiotics due to overgrowth of C.Diff

Therapy - hydration and vancomycin or metronidazole

vaccines: amantadine (symmetrel) and Rimantadine (Flumadine) -- against Influenza A

Drugs: Neuraminidase inhbiitors - slow virus growth - zanamivir (relenza) & oseltamivir (tamiflu)

Nucleoside reverse transcriptase (NRTIs) or protease inhibitors

Extend latent phase of HIV by keeping CD4 up and viral load down

superificial (athlete's foot)

pulmonary infections (pneumonia)

CNS (meningitis, encephalitis)

systemic

anaerobes - clostridia

no cell wall: mycoplasma

obligate intracellular: ricketsia, chlamydia

Application of crystal violet

Application of iodine (blue - gram pos)

Alcohol wash

Application of safranin (red - gram neg)

prion

Transmissible spongiform encephalopathies (TSE) - creutzgeldt-Jakob disease or Bovine spongiform encephalopathy

protein

receptors

replicate the genome

assemble new viral particles

achieve release

RNA:

influenze, HIV, polio

DNA:

Herpes, hep B, adenovirus

A - 4

 B - 5

C - 3

D - 1

E - 6

F - 7

G - 2

gram pos organisms

gram neg cocci (neisseria)

Treponema pallidum (syphilis)

weaknesses: staph aureus, gram neg rods/bacilli

otitis, UTI, dental prophylaxis

side effects: rash (esp ampicillin)

Hypersensitivity (5% incidence) - rash, angioedema, anaphylaxis

Diarrhea

Nephritis

cefazolin (ancef, kefzol)

cefoxitin (mefoxin)

ceftriaxone (rocephin)

cefepime (maxipine)

tetracyclines

aminoglycosides

macrolides

Doxycycline (Vibramycin)

All tetracyclines end in "cycline"

food dairy antacids

anti-inflammatory action

pregnancy and children (8-14)

dental enamel dysplasia and discoloration

growth inhibation & bone deformity

photosensitivity

all are potentially ototoxic and nephrotoxic

toxicity increased by loop diuretics

sulfaonamides

trimethoprim

co-trimoxazole (septra, bactrim)

B-Lactams - penicillins, cephalosporins

also, vancomycin

ampicillin

amoxicillin

tetracyclines

aminoglycosides

macrolides

fluroquinolones

AKA DNA gyrase inhibitors

isoniazid

Rifampin

Ethambutol

nucleoside reverse transcriptase inhibitors

protease inhibitors

prevent HIV DNA from inserting in host DNA via "integrase inhibitors" - Raltegravir

Used in pts with multi-drug resistant HIV

CD4 counts less than 200-350 cells/cubic mL

HIV RNA levels > 100,000 copies/mL

Diagnosis of AIDS established

1. RBC production problems

- nutritional deficiency

- loss of stimulation (erythropoietin)

- toxiciity

- neoplasia

Accelerated loss of RBC (often due to low iron in women)

- shortened life span (normal is 100-120 days)

- bleeding

aplastic

due to loss of hematopoietic stem cells (apoptosis)

Immunosuppresion, bone marrow transplant if that doesn't wrk

it's  possible for enough bone marrow to be occupied by cancer to get anemia

more likely: myeloproliferative disorder

leukemias

lymphoma

multiple myeloma

polyctythemia

thrombocythemia

acute myeloid

chronic myeloid

acute lymphoid

chronic lymphoid

Hodgkin's - most common

- young adults

Non-Hodgkins

multiple myeloma

polycythemia

thrombocythemia

in high partial pressure environments such as lthe lungs, Hgb lets go of O2

In low partial pressure environments such as the periphery, Hgb tends to hold on to O2

autosomal recessive - HgbA - HgbS

Homozygous = sickle cell diesaese (1/400 blacks in US)

heterozygous = asymptomatic (8% of blacks)

Missense mutation

globin

autosomal recessive

B-thalassemia major

B-thalassemia minor

nutrients (glucose, vitamins, minerals)

electrolytes

hormones

proteins (albumen, coagulation proteins, carrier proteins)

drugs

RBC

WBC

platelets

adult: 2 alpha chains + 2 beta chains

Fetal: 2 alpha chains + 2 gamma chains

All have 1 oxygen-carrying heme group per chain

erythrocytes

megakaryocytes (platelets)

Granulocytes

monocytes

NK cells

dendritic cells

T lymphs

B lymphs

granulocytes: basophils, neutrophils, eosinophils

agranulocytes: macrophages (monocyts), T & B lymphocytes

megaloblastic

Large RBCs, hypersegmented neutrophils, ineffective erythropoiesis (impaired DNA synthesis)

intrinsic factor (B12 absorber)

megaloblastic anemia

neurologic

B12 is cofactor in activation of folate

Folate supplements can correct the anemia but not repair neurologic damage

Diagnosed with Schilling test: give pt oral radiolabeled B12 & measure excretion.. then give oral intrinsic factor. if absorption increases = pernicious anemia

G6PD

malaria

bilirubin

iron/folate

Polycythemia

altitude inadaptation, sports doping

Hypothalamus: vasopressin, oxytocin

Anterior pituitary: ACTH, TSH, FSH, LH, Prolactin, Growth hormone

produce thyroid hormone from follicular cells

T3 - triodothyronine - main fxnal hormone

T4 - thyroxine - converted to T3 in tissues

Receptors throughout body - energy utilization, protein sythesis, sensitivity to other hormones

endemic

toxic nodular goiter

advanced cancer

Papillary - most common and most beingn

Follicular - benign

Medullary - benign

Anaplastic - most lethal and rare

surgical excision (thyroidectomy)

radioactive iodine

lifelong thyroid hormone replacement

grave's disease

toxic nodular goiter

TSH - low

T4 - high

autoimmune - sometimes pos

Symptoms: restlessness, anxiety, insomnia, tremor, weight loss, heat intolerance

severe hyperthyroidism

hypokalemic periodic paralysis

grave's disease

much more common in women

exophthalmos

parasympathetic

sympathetic

sympathetic

beta blockers - propranolol

stop t3/t4 production - thioamide drugs, prevent t3/4 release - potassium iodide

cure: thyroid excision or ablation

monitor TSH levels, which are initially zero in hyperthyroid pt

As T4 falls, TSH rises

When TSH rises above normal - begin thyroid hormone replacement therapy wiht thyroxine

primary - due to failure of thyroid gland itself, has nothing to do with TSH. Accounts for 99% of cases

Secondary - due to failure of pituitary to release normal amounts of TSH. very rare.

T4 low

TSH very high

poor memory

inability to concentrate

weight gain

cold intolerance

Hashimoto's thyroiditis

drug-induced hypothyroidism

compensated primary hypothyroidism

caused by failure of negative feedback loop from thyroid to pituitary

Cushing's syndrome

increase gastric acid and pepsin production

increase bone loss

muscle weakness

mental status change - makes you feel good

anti-nausea

resistance to stress

raise bp

lowers lymphocyte/monocyte levels

weight gain

impaired healing

bone loss

edema

peptic ulcers

euphoria

hallucinations

fatigue

muscle weakness

elevated glucose levels

cataracts

central obesity

moon facies

iatrogenic

pseudo-hyperparathyroidism

autoimmune hypoparathyroidism

low

high

low

treatment: replacement with vit d analogs to absorb Ca in gut

primary

secondary

high

high

low

high

variable

variable

high

high

hyper: chronic renal disease

hypo: iatrogenic

hyperglycemia

insulin

exocrine - secrete digestive enzymes

endocrine - islets of langerhans secrete insulin, glucagon, others

glycogen

glycogen

protein

triglyceride

autoimmune

beta

polydipsia

polyuria

polyphagia

Also: weight loss, fatigue

Complications: ketoacidosis, cardiovascular dx, renal dx, retinopathy/blindness, neuropathy

sulfonylurias

metformin (glucophage) and Glitazones

NPH, glargine

GLP-1 substances

weight in kg divided by square of height in meters

weight in lbs x 700 divided by square of heigh in inches

white

brown

white

aromatase

women: fewer hot flashes. greater risk for breast/uterine cancer

men: gynecomastia, prostate problems

leptin

inflammation

Peripheral vascular disaese

heart disease

Reduce HR

Reduce contractility

Reduce venous return

Reduce PVR via vasodilation

Both of these can be reduced by reducing sympathetic activity

constriction

increased

aldosterone

lipoprotein

lipid

cholesterol

LDL bad

HDL good

Main goal: lower ldl, raise HDL

essential

pheochromocytoma

none!

must be diagnosed via several BP tests

CO

PVR

diuretics

sympatholytic drugs

vasodilators

renin-angiotensin-aldosterone inhibitors

K+

ACe inhibitors

Beta blockers

ischemia

vessel stenosis or occlusion

acute ischemia

subacute intermittent ischemia

chronic ischemia

STEMI = acute MI with ST segment elevation

NSTEMI = acute MIwithout ST elevation

coronary blood flow

atherosclerosis

plaque rupture

early morning - BP is at diurnal peak

increased viscosity due to overniight fast

cortisol at secretion peak

plus morning exercise = bad news

likely to have atypical presentation

gastric symptoms

PCI (percutaneous coronary intervention)

thrombolytic therapy

both reperfuse tissues wtih O2

stable angina - unmet O2 demand to myocardium or coronary atherosclerosis

unstable angina

variant

anginal episode

If it lasts longer than 20 min, it's likely an MI

CHF

ischemic or HTN disease - more people survive MI's than before but then they end up with CHF

ischemia

remodeling

ischemia

activity

HTN

Sodium

ACE inhibitor or ARB or Beta blockers (if no pulm edema)

atrial septal defect

pulmonary stenosis

tetrology of fallot

coarctation of aorta

Thrombosis

embolism

PE

venous stasis

hypercoagulable state

vascular injury

Also - surgical procedures such as abdominal or pelvic but especially JOINT REPLACEMENTS

rate abnormalities

ectopic depolarizaitons

deviant pathways (reentry)

Na channel

Beta

K+ channel

Ca 2+ channel

atrial fibrillation - creates irregularly irregular pulse

clots in atria can travel to brain and cause stroke in A fib pts