What is this an image of?

[image]

Nodular sclerosing Hodgkins Lymphoma

equally common in men and women

young adults

good prognosis

Multiple Myeloma:mainly proloferation of IgG, lytic bone lesions that you don't see in Waldenstrom's

____________________________________________

Waldenstroms Macroglobulinemia: monoclonal proliferation of IgM

Monoclonal proliferation that doesn't cause end organ damage (yet)

Patients need to be monitored closely bc this can progress to Multiple Myeloma

Patient has symptoms of anemia, hypercalcemia and bone pain. Bone marrow biopsy shows large amounts of plasma cells

What would you see on urinalysis?

Pt has Multiple Myeloma

urinalysis shows nothing bc Bentz-Jones proteins don't show up on a UA

You can see the monoclonal antibody spike on UPEP: Urine Protein Electrophoresis

CML

(Philadelphia CreaM cheese)

Type II:

Antibodies against self

Type III:

Antibodies agains foreign antigens -->Ab-Ag complexes deposited in tissues

What is the enzyme deficiency in Lesch-Nyhan?

What is the treatment?

HGPRT (Hypoxanthine guanine phosphoribosyltransferase)

[image]

[image]

Treatment: Allopurinol

[image]

Vitamin D increases uptake of Calcium in the intestine by increasing expression of calcium binding protein

Stimulates PTH dependent reabsorption of Calcium at the distal tubules of the kidney

Stimulates bone reabsorption and rebuilding

[image]

Adults: Osteomalacia

Children: Ricketts

excess of unmineralized bone matrix

[image][image][image][image]

Post-translationa modification of various clotting factors

Factors II, VII, IX, X

Proteins C & S

Prothrombin

[image]

hemorrhagic disease

(lack of clotting factors)

Why are newborns particularly prone to vitamin K deficiency?

What prophylactic measures can be taken to reduce the incidnece of this problem?

Newborns don't have microbes in gut to produce vitamin K, and mommy's milk only provides 1/5th of the need.

It is recommended that newborns recieve a single IM dose of Vitamin K at birth

Coumadin

Aticonvulsants

Antibiotics (due to loss of gut bacteria)

Retinol, Retinal

Beta-carotene (cleaved in intestine to yield 2 molecules of retinal)

Retinoic Acid (unusuable by the body)

[image]

They are stored in the liver until needed

Transported via plasma retinol-binding protein (RBP)

[image]

Vision [image]

Growth[image]

Reproduction (spermatogenesis & prevent fetal resorption)

[image]

Maintenance of epithelial cells (esp. mucus secreting cells)[image]

Acne (Isotretinoin/Accutane)

Psoriasis

reduce aging

Night blindness

Xeropthalmia -->corneal ulceration and blindness

[image]

[image]

Keratomalacia (wrinkling, clouding of cornea)

[image]

Bitot's Spots (dry, silver-gray plaques on bulbar conjunctiva)

[image]

Headache, nausea, vomitting, stupor

dry, pruritic skin

enlarged, possibly cirrhotic liver

bone and joint pain

increase in intracranial pressure

Pregnancy (inhibits neural crest cell migration)

Smokers (increases chances of lung cancer)

Chronic Kidney Disease

Osteoperosis

Pseudo tumor cerebri

(increased CSF pressure)

[image]

Antioxidant in blood

Required for conversion of Dopamine to NE

required for Collagen synthesis

Assists in Iron absorption

(Scurvy)

sore, spongy gums

lose teeth

fragile blood vessels-->hemorrhages

swollen joints (bleeding into joint spaces)

Impaired wound healing

Anemia

Antioxidant that prevents free radicals from damaging RBCs and other cells

aka alpha-tocopherol

Spinocerebellar degeneration-->Ataxia

Peripheral neuropathy and proximal muscle weakness

Vitamin C

Vitamin E

Vitamin A (Beta Carotene-->Retinal)

Reduced glutathione

What are the symptoms of Zinc Excess?

Zinc deficiency?

B9

Synthesis of purines (A,G) anf thymine

[image]

What is the intracellular storage form of folic acid?

What is the biologially active form?

intracellular storage form:

N-methyl folate

Biologically active:

Tetrahydrofolate

Folate deficiency:

Neural Tube defects

Growth Failure

Megaloblastic Anemia (macrocytic anemia characterized by elevated # of megaloblasts in the marrow)

[image]

Folate and B12

either seperate or combined

*check serum levels (folate may be reduced in both bc B12 def. can cause a decrease in folate)

COBALT

Cobalamin aka B12

Amino acid and folate synthesis:

Homocysteine & Methyl-THF-->methionine &THF

*required for SAM to function*

Citric Acid Cycle and Fatty Acid production

Methylmalonyl CoA (Coenzyme A)-->Succinly CoA

Megaloblastic Anemia

CNS problems

Atrophy of stomach fundic glands-->achlorhydria

and replacement of the gastric epithelium with mucus secreting goblet cells tht resemble those lining the large intestine (intestinalization)

Homocystinuria and methylmalonic acid in urine

Name two malabsorption problems of the distal ileum that cause B12 deficiency

How would you treat B12 deficiency?

Crohn's disease

Celiac sprue

Tx for B12 def: IM injection of cyanocobalamin

Pyridoxine

convulsions

hyperirritability

peripheral neuropathy

glossitis

angular chelitis

[image]

Thiamine: B1

Retinol, retinal: A

Pantothenic acid: B5

Pyridoxine :B6

a-tocopherol: E

Folic acid: B9

Niacin: B3

Riboflavin: B2

Ascorbic acid: C

Cobalamin: B12

"The Rich Never Pan Pyrite Filled Creeks"

1.3.5.6.9.12

Beriberi (dry and wet) : where polished rice is makor component of diet

Wernicke-Korsakoff syndrome: chronic alcoholism

What are the two biologically active forms of riboflavin?

What is the role of these molecules?

Flavin mononucleotide (FMD)

Flavin Adenine Dinucleotide (FAD)

Cofactors for redox reactions

Chelitis/ Angular stomatitits

Dermatitis

Glossitis

*these symptoms common in Fe, B2,B3,B9, B12

Angular stomatitis is common in denture wearers too

NAD+

NADP+

Cofactors for redox reactions

Tryptophan

Pellagra

Corn lacks tryptophan: common in pts that only eat corn

it inhibits lipolysis in adipose tissue

less fatty acids circulating and

less LDL produced

Peripheral vasodilation (flushing)

can be lessend by taking aspirin with niacin

Pantothenic acid (B5) is a component of CoA which functions in the transfer of Acyl groups

No deficiency disease asscoiated with B5

Glycoprotein avidin in egg whites prevents absorption of biotin (20 egg whites per day)

Antibiotics (gut bacteria make biotin)

What cytokine(s) matches the following statement?
Promotes B cell growth and differentiation

Produced by Th1 cells

Produced by Th2 cells

Secreted by helper T cells and activates macrophages

Pyogens secreted by monocytes and macrophages

Enhances synthesis of IgE and IgG

Enhances synthesis of IgA

Released by virally infected cells

Promotes B cell growth and differentiation- IL-4, IL-5

Produced by Th1 cells- IL-2, IFN-gamma

Produced by Th2 cells -IL-4, IL-5, IL-10

Secreted by helper T cells and activates macrophages-IFN-gamma

Pyogens secreted by monocytes and macrophages- IL-1, IL-6, TNF-alpha

Enhances synthesis of IgE and IgG- IL-4

Enhances synthesis of IgA- IL-5

Released by virally infected cells- IFN-alpha, IFN-beta

anemia

abdominal pain

diarrhea and nausea

encephalopathy

wrist drop or foot drop

lead lines on the gums

Duodenal Atresia

Hirschsprungs

Annular Pancreas

Celiac Disease

Bacteroides Fragilis (gram-, facultative anaerobe, ferments sugar into lactic acid)

E.Coli is 2nd

Fecolith Obstruction (common in adults)

Lymphoid hyperplasia after viral infection (in children)

symptoms: McBurney's point :possible fever, diffuse periumbilical pain that travels to th right lower quadrant with rebound tenderness and leukocytosis

have to rule out ectopic pregnancy in women

What is the most common tumor of the apendix?

Symptoms?

Carcinoid Tumor

BFDR:

Bronchospasm

Flushing

Diarrhea

Right sided heart valve disease

can occur in bronchial tree, small intestine or appendix

Hyperplastic polyps

found in the recto-sigmoid area usually

do not have a precancer risk

[image][image]

Tubular Adenomas

Tubular Villous Adenomas

Villous Adenomas (most villainous)

need to be removed and analyzed

multiple benign hamartomas throughout GI tract

hyperpigmented lips, mouth, genitalia

increased risk of cancers (colorectal, tumors, ovarian cancer and breast cancer)-- 1/2 in 60th decade

[image][image][image]

KrAPp

K-ras

APC gene mutation (Familial Adenomatous Polyposis)

loss of p53

Colon cancer is always #3

what does this mean?

3rd most common cancer in men and women

3rd most common cancer killer in US

IBD

Ulcerative Colitis

Crohn's

Tobacco

Adenomas

Obesity

High fat, Low fiber diet

What is Gardner's Syndrome?

Subtype of familial adenomatous polyposis (FAP or classic FAP (APC related)). In people with Gardner syndrome, masses of noncancerous tissue tend to form in many different organs, such as:

Multiple adenomatous colon polyps. An adenomatous polyp is an area where the normal cells that line the inside of the colon and begin to make mucous and form a mass on the inside of the intestinal tract.

Benign (noncancerous) tumors, including:

sebaceous cysts (closed sac filled with liquid found under the skin)

epidermoid cysts (lumps in or under the skin often filled with liquid)

fibromas (fibrous tumors)

desmoid tumors

(fibrous tumors that can develop anywhere in the body)

osteomas (bony growths, usually found on the jaw)

[image]

Familial Adenomatous Polyposis associated with CNS tumors

specifically medulloblastoma

[image]

The sigmoid colon

[image]

Metronidazole +

-TMP/SMX

-Ciprofloxacin

-or Levofloxacin

perforation/tear of gut lumen

or trauma from the outside (obvious)

[image]

Volvulus is most common in this portion of the colon and in this population

elderly

cecum and sigmoid colon

twisting of the colon around its mesentery

causing ischemia and necrosis

pectinate/dentate line

[image]

inflammation of perianal region usually due to fecal matter in the area for a prolonged length of time

can be assoc. with ulcerative colitis

steroid cream/lotion

distal colon and moves proximally

autoimmune

always has rectal involvement

inflammation

lose haustra

crypt abscesses, ulcers, bleeding

[image]

60-year-old female with rheumatoid arthritis and no alcohol history presents with fatigue and right abdominal pain, lab studies reveal high levels of ANA and ASMA, elevated serum IgG levels, and no viral serologic markers.

What disease?

Liver biopsy on a 23-year-old female with elevated levels of LKM-I antibodies, no alcohol history, and no viral serologic markers reveals infiltration of the portal and periportal area with lymphocytes. What do you suspect?

most common: E.Coli

2nd most common: Klebsiella

Aspiration pneumonia

DiAbetics

Alcoholics (aspiration from vomitting)

Abscess in the lungs

E.Coli (80%)

Staph Saprophyticus

Klebsiella

Proteus (urease and staghorn calculi)

What is the mechanism of action of Sulfonamides?

SE?

what is it used for?

PABA antimetabolite

inhibits folic acid synthesis by inhibiting dihydropteroate synthetase

bacteriostatic

covers:

gram-

gram+

nocardia

chlamydia

UTIs

usually used with TMP: combo also called bactrim

SE:

HSRs

G6PD pts can have hemolysis

photosensitivity

interstitial nephritis

kernicterus (dont give to pregnant women or infants)

Steven's Johnsons

can displace drugs from albumin (like warfarin)

can get resistance

SAT for photos

Sulfonamides

Amidarone

Tetracyclines

Seizure Drugs

Ethosuximide

Lamotrigine

Carbamazapine

Phenobarbital

Phenytoin

Sulfa Drugs

Celecoxib

Furosemide

Probenecid

Thiazides

TMP-SMX

Silfasalazine

SUlfonylureas

Acetazolamide

Penicillin Drugs

Allopurinol

think abbreviations

UTIs

(SS)Shigella and Salmonella infections

MRSA (skin infections)

AIDS (prophylaxis pneumocystis jiroveci pneumonia CD4<200)

all side effects can be reduced by adding folic acid to the diet/supplement

TMP: antibacterial

Methotrexate: anti-inflammatory

Nitrofurantoin

safe to use in pregnant women

What is the mechanism of action of Flouroquinolones?

Toxicity?

Uses?

(-floxacin)

inhibits DNA gyrase (Topoisomerase II)

do not take with antacids

used for respiratory tract infections and UTIs caused by:

gram- (1st and 2nd)

pseudomonas

gram+ (3rd and 4th)

Toxicity: contraindicated in pregnancy and children (except kids with CF under monitoring) due to arthropies (lones and bones), tendonitis, tendon rupture

Salmonella and a lot of the other diarrhea causing bacteria

antibiotics do not shorten illness so supportive care is recommended. Antibiotics only if patient is at risk for invasive disease

Somatic O antigen: Lipopolysaccharide in outer membrane

H Antigen: in flagella

K antigen: virulence factor part of polysaccharide capsule

Metronidazole

Oral Vancomycin

What infectious agent most likely corresponds to the following statement?

1. Food poisoning due to mayo sitting out too long
2. Diarrhea caused by gram- nonmotile organism that does not erment lactose
3. rice-water stools
4. Diarrhea cuased by C or S shapped organism
5. Diarrhea transmitted from pet feces
6. Food poisoning due to reheated rice
7. Diarrhea caused by gram- motile organism that doesn't ferment lactose
8. Most common traveler's dairrhea
9. Diarrhea after a course of antibiotics
10. Diarrhea caused by gram- lactose fermenting bacteria, no fever
11. Diarrhea caused by gram-comma shaped organism, no fever
12. Diarrhea+recent inestion of steam water
13. Food poisoning from undercooked hamburger meat

1.Staph aureus

2. Shigella

3.Vibrio Chlolera or ETEC

4.Campylobacter

5. Yersinia Enterolitica

6.Bacillus cereus

7. Salmonella

8. ETEC

9.C.diff

10. E.Coli

11. Vibrio Cholera

12. Giardia lamblia or Entamoeba Histolytica

13. E.Coli 0157:H7

Giardia Lamblia

Entamoeba hisolytica

Trichomonas

Gardenella Vaginalis

Anaerobes

H.Pylori

Disulfaram-like reaction

alcohol can't be fully metabolized-->build up of aldehydes-->flushing, sweating, nausea, HA, Hypotension

What protozan matches the following statement?

Cause of malaria

Most common protozoal infection in U.S.

Cause of Chagas disease

Amoebic dysentery

African Sleeping Sickness

Diarrhea in campers and hikers

Transmitted in raw meat or infected cat feces

Transmitted by sandflies

Causes vaginitis

Cause of Malaria: Anopheles Mosquito: Plasmodium Falcipirum, Vivax, Ovale

Most common protozoal infection in US: Giardia or Trichomonas

Cause of Chaga's: Trypanosoma Cruzi

Amoebic dysentery: Entamoeba histolytica

African Sleeping Sickness:
Trypanosoma Rhodesiense

Trypanosoma Gambiense

Diarrhea in campers and hikers:
Giardia Lamblia

Transmitted in raw meat or infected cat feces:
Toxoplasmosis Gondii

Transmitted by sandflies: Leishmania

Causes Vaginitis: Trichomonas Vaginalis

Entamoeba Histolytica

What is the name of the following stage in the malaria life-cycle?

Looks like a diamond ring

ruptures the cell host

replicating intracellularly

Form injected from the Anopheles mosquito

Banana-shaped

Looks like a diamond ring: Trophozoite (in RBCs)

Ruptures the host cell: Merozoite (in heaptocytes and RBCs)

Replicating intracellularly: Schizont

Form injected from the Anopheles mosquito: Sporozoite

Banana shaped: Gametocyte of plasmodium falcipirum

repetitive rupturing of RBCs

What helminth matches the following statement

-Most common helminthic infection in the US

-One quarter of the wolrd infected with it

-Snail host, "swimmer's itch"

-Most common predisposing factor for bladder cancer in 3rd world countries

-Contracted by eating undercooked fish and causes an inflammation of the biliary tract

-Soil-->enters through skin-->venous blood supply-->lungs-->coughed into pharynx-->swallowed into the intestines where they reside

-Hookworm

-Giant roundworm

-Contracted by eating undercooked crabmeat and causes inflammation of the lung

-pork tapeworm

-responsible for lymphatic filariasis

-adult patient from Mexico with new onset of seizures and brain calcifications

-hematuria in patient from 3rd world country

-Most common helminthic infection in the US:

Enterobius vermicularis

-One quarter of the wolrd infected with it

Ascaris Lumbricoides

-Snail host, "swimmer's itch"

Schistosoma

-Most common predisposing factor for bladder cancer in 3rd world countries

Schistosoma haematobium

-Contracted by eating undercooked fish and causes an inflammation of the biliary tract

Clonorchis

-Soil-->enters through skin-->venous blood supply-->lungs-->coughed into pharynx-->swallowed into the intestines where they reside

Strongyloides

-Hookworm

Ancylstoma

-Giant roundworm

Ascaris Lumbricoides

-Contracted by eating undercooked crabmeat and causes inflammation of the lung

Paragonimus Westermani

-pork tapeworm

Taenia Solium

-responsible for lymphatic filariasis

Wuchereria bacrofti

-adult patient from Mexico with new onset of seizures and brain calcifications

Taenia solium

-hematuria in patient from 3rd world country

Schistosoma haematobium

What medication is used to treat the following parasitic infection?

• Giardia, Entamoeba, Trichomonas
• Most malarias
• Plasmodium vivax or ovale
• Resisitant malarias
• Most all flukes and tapeworms
• Hookworm, pinworm, roundworm
• Chagas disease
• Best guess for roundworms
• Leishmaniasis

Giardia, Entamoeba, Trichomonas: Metronidazole

• Most malarias: Chloroquine

Plasmodium vivax or ovale: Chloroquine+Primaquine

• Resisitant malarias:

Quinidine+Doxycycline/Mefloquine/Atovaquone-proguanil/Artemether-lumefantrine

• Most all flukes and tapeworms: Praziquantel

• Hookworm, pinworm, roundworm: Benzamidazoles/Pyrantel pamoate

• Chagas disease: Nifurtimox

• Best guess for roundworms: Benzamidazoles

• Leishmaniasis:

Sodium Stibogluconate (cutaneous)
Liposomal Amphotericin B (visceral)

Which protozoa are responsible for the following disease?

• Chagas
• Protozoal Vaginitis
• Malaria
• Birth defects
• Bloody Diarrhea
• Foul smelling diarrhea, flatulence, bloating

• Chagas : Trypanosoma Cruzii
• Protozoal Vaginitis: Trichomonas
• Malaria: Plasmodium species
• Birth defects: Toxoplasma
• Bloody Diarrhea: Entamoeba histolytica
• Foul smelling diarrhea, flatulence, bloating: Giardia Lamblia

Septal nucleus

Mamillary bodies

Fornix

Hippocampus

Cingulate gyrus

What are the 3 most common cancers in men and women in order?

Highest Mortality?

Men:

1.Prostate (2nd highest mortality)

2.Lung (1st highest mortality)

3.Colon

Women:

1.Breast (2nd highest mortality)

2.Lung (1st highest mortality)

3.Colon

4.Uterus

Pancreatic cancer has the 4th higest mortality in both men and women

What type of cancer is associated with the following tumor suppressor genes?

• Rb
• DPC
• DC
• p53
• APC
• WTI
• BRCA1, BRCA2
• RET

• Rb : Retinoblastoma, Osteosarcoma

DPC : Pancreatic cancer (deleted)

• DCC : Colon cancer (deleted)

• p53 :most all cancers, Li Fraumeni Syndrome

• APC : Familial Adenomatous Polyposis/ Colorectal cancer

• WTI :Wilm's Tumor 1

BRCA1, BRCA2 :Breast cancer and ovarian cancer

RET: MENIIa and IIb, papillary thyroid cancer

K-Ras:

Kolon, lung and PanKreatic

H-Ras:

Bladder and Kidney tumurs (Hematria)

N-Ras:

melanomas, hematologic malignancies

follicular thyroid cancer

AR disorder caused by an inability of the DNA to repair thymidine dimers by UV damage causing mutations and activating proto oncogenes-->skin cancer

avoid sunlight

Children of the night

[image]

What neoplasms are associated with the following conditions?

• Hashimoto thyroiditis
• Plummer Vinson Syndrome
• Tuberous Sclerosis
• Ataxia telangiectasia
• Paget disease of bone

• Hashimoto thyroiditis: Lymphoma

• Plummer Vinson Syndrome: esophageal SCC

• Tuberous Sclerosis: Cardiac Rhabdomyoloma, Astrocytoma, Angiomyolipoma

• Ataxia telangiectasia:Leukemias and Lymphomas

• Paget disease of bone: Osteosarcoma, fibrosarcoma

HNPCC :germline mutations (Lynch Syndrome)

Ataxia-Telangiectasia

Xeroderma Pigmentosa: defect in excision repair to fix dimers from UV

"HAX Repair shop"

Myeloid leukemias: AML and CML

Thyroid cancer in young

Squamous cell carcinoma of the skin

Basal Cell carcinoma of the skin

Melanoma

(UVB is the Bitch- the most problematic)

What cancers are associated with the following conditions?

Down's Syndrome

Albinism

Chronic Atrophic gastritis

Tuberous Sclerosis

Solar keratosis

Barrets Esophagous

Plummer-Vinson Syndrome

Cirrhosis

Ulcerative Colitis

Paget's disease of bone

Acanthosis Nigricans

Achalasia

Sjorgens

Down's Syndrome: ALL and AML

Albinism: SCC, BCC, Melanoma

Chronic atrophic gastritis: gastic adenocarcinoma

Tuberous sclerosis: Cardiac rhabdomyoloma, Astrocytoma, Angiomyolipoma

Solar keratosis: SCC

Barrett's Esophagus: Adenocarcinoma

Plummer-Vinson: Esophageal webs-->SCC

Cirrhosis: HCC

Ulcerative Colitis: Colon Cancer

Paget's Disease of bone: Osteosarcoma, fibrosarcoma

Acanthosis Nigricans: visceral malignancies

Achalasia: SCC of esophagus

Sjorgens: B cell lymphoma

16 and 18

(you are allowed to do two things that kill -drive and smoke)

Oncogenic Bacteria and Helminths are associated with what neoplasm?

• Strep, bovis
• H.Pylori
• Schistosoma haematobium
• Clonorchis sinensis

• Freshwater snail: Schistosoma (schistosomiasis)

• Ixodes tick: Babesia (Lyme's disease)

• Reduviid bug: Trypanosoma Cruzii (Chagas)

• Anopheles mosquito: Plasmodium species (Malaria)

• Sandfly: Leishmania donavani (Leishmaniasis)

• Tsetse fly: Trypanosoma brucei (African Sleepig Sickness)

Celecoxib

Probenicid

Loop Diuretics

Thiazide Diuretics

Acetazolamide

Sulfonamide

Sulfonylureas

Sulfasalazine

bFGF

VEGF

Bevacizumab (cancer drug that inactivates VEGF of tumor cells)

nuclear chromatin clumping

high nucleus:cytoplasm ratio

prominient nuclei

multiple mitotic figures

irreversible change and malignant

[image][image]

• Benign tumor of epithelium: Adenoma or Papilloma

• Malignant tumor of blood vessels: Angiosarcoma

• Benign tumor of bone : Osteoma

• Malignant tumor of smooth muscle : Leiomyosarcoma

"Lot of Bad Stuff Kills Glia"

Lung

Breast

Skin (Melanoma)

Kidney (Renal cell carcinoma)

GI tract tumors

"Cancer Sometimes Penetrates Benign Liver"

Colon

Stomach

Pancreas

Breast

Lung

Poor Tired Barney loves kids

Prostate (blastic)

Testes/Thyroid

Breast (lytic or blastic)

Lung

Kidney

What are the four cancers associated with this?

[image]

Psamomma bodies

"Sam Makes Me Pissed"

Serous Cystadenoma of the ovary

Malignant Mesothelioma

Meningioma

Papillary Thyroid Cancer

What is the most common cause of hypercalcemia?

What cancers may cause hypercalcemia?

Primary hyperparathyroidism

cancers:

SCC of lung, head and neck

multiple myeloma

breast cancer

renal cell carcinoma

metastatic disease to bones

What neoplasm is most commonly responsible for the follwoing paraneoplastic syndromes:

• ACTH-->Cushings Syndrome
• Erythropoietin-->Polycythemia
• ADH-->SIADH

• ACTH-->Cushings Syndrome Small cell lung cancer

• Erythropoietin-->Polycythemia Renal cell carcinoma, hemangioblastoma, HCC, Pheochromocytoma

ADH-->SIADH Small cell lung cancer and any intercranial lesion

What CD surface marker fits the following statement?
• Displayed only by helper T cells

• Displayed only by cytotoxic T cells

(and suppressor T cells)

• Found on all T cells (except NK cells)

• Used to ID B cells

• Found on all NK cells &binds the constant region of IgG

• Inhibits complement C9 binding

• Endotoxin receptor found on macrophages

• Displayed only by helper T cells: CD4

• Displayed only by cytotoxic T cells: CD8

(and suppressor T cells)

• Found on all T cells (except NK cells): CD3, CD2

• Used to ID B cells: CD19,CD20,CD21

• Found on all NK cells &binds the constant region of IgG: CD16

• Inhibits complement C9 binding: CD55, CD59

• Endotoxin receptor found on macrophages: CD14

alfatoxins

nitrosamines

alcohol

Tamoxifen

Raloxifen

only high risk candidates bc they have their own problematic side effects

every 3 years until 65 yo.

or unless pt has hysterectomy then you don't need one at all bc it checks for cervical cancer and this person doesn't have one.

CD8+ cytotoxic T cells

NK cells

both secrete IFN-gamma which activate macrophages which can kill cancer cells

Macrophages

selective outgrowth of antigen-negative variants

reduced expression of MHC molecules (hidden from CD8 T cells , but NK cells still kill them tho)

lack of co-stimulation

Immunosuppression (TGF-beta)

Antigen masking

Apoptosis of the cytotoxic T cells (FasLigand binds to death receptor on T cell)

Which cancer is associated with elevated alk phos?

Which cancer is associated with beta-HCG?

alk phos:

Paget disease, Mets to bones, bilary disease

beta-HCG:

choriocarcinoma/hydatiform mole

What medication is used to treat the following parasitic infection?

• Gardia, Entamoeba, Trichomonas

• Plasmodium vivax or ovale

• Most flukes and tapeworms

• Hookworm, pinworm, roundworm

• Gardia, Entamoeba, Trichomonas

metronidazole

• Plasmodium vivax or ovale

Chloroquine + Primaquine

• Most flukes and tapeworms

Praziquantel

Hookworm, pinworm, roundworm

Bendazoles

Pyrantel pamoate

Methotrexate

what is it?

what does it do?

How is it used?

Toxicity?

Folic acid analogue

[image]

inhibits dihydrofolate reductase

S phase specific

uses: cancer, immunosuppression autoimmune, uterine pathology (choriocarcinoma/hydaditiform moles), abortifacient

toxicity: myelosuppression reversible with leucovorin

5-Flourouracil

What is it?

used for?

Toxicity?

[image][image]

Pyrimidine Analagoue

S phase specific antimetabolite

used: actinic keratosis (premalignant skin lesion)

topical for basal cell carcinoma

toxicity: myelosuppression reversible with thymidine

photosensitivity (think flowers and photsynthesis)

6-Mercaptopurine

What is it?

Used for?

Toxicity?

[image]

6MP and not one is PURE

Purine analogue

S phase specific antimetabolite

inhibits PRPP synthetase

metabolized by xanthine oxidase

toxicity: increases with allopurinol

*6-TG, similar to 6MP, but can be given with allopurinol*

Cytarabine

what is it?

what does it do?

Pyrimadine analogue

[image]

inhibits DNA polymerase

S phase specific antimetabolite

chemotherapy mostly of WBC cancers (AML)

Dactinomycin

"Children act out for childhood tumors"

cell cycle nonspecific agent

intercalates DNA

Toxicity: Skin eruptions, hyperkeratosis, myelosuppression

onion skin bone growth

[image]

Which chemotherapeutics are characterized for cardiotoxicity?

How can you prevent it?

Doxorubicin and Daunorubicin

(and Trastuzumab)

"Doxo and Dauna where in love and broke their hearts bc no Trast (trust)"

Doxo and Dauno are cell cycle nonspecific agents

oxidize free radicals and noncovalently intercalate DNA

Doxo/Dauno USE:

Hodgkin lymphoma

Myeloma

to prevent cardiotoxicity: dexrazoxane, iron chelating drug

Bleomycin

G2 phase specific agent

generates free radicals

use:

testicular cancer

hodgkin disease

Etoposide

Teniposide

Inihibits Topoisomerase II and increase DNA degradation

(flouroquinolones also do this)

use:

testicular cancer

prostate cancer

small cell lung cancer

Eradicate Ball Cancer

Etoposide

Bleomycin

Cisplatin

methotrexate: folic acid analog

inhibits dihydrofolate reductase

[image]

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5-flourouracil: pyrimidine analog

inhibits thymidylate synthase

[image][image]

[image]

Cyclophosphamide

Ifosfamide

Carmustine, Lomustine, Semustine

Streptozocin

Cisplatin, Carboplatin, Oxaloplatin

Busulfan

Cyclophosphamide (alkylating agent)

[image]

-also increases risk of transitinal cell cancer of bladder

-prevent hemorrhagic cystitis with Mesna

binds to acrolein metabolite

Put Nitro in your Must-ang

[image] 

carmustine

lomustine

semustine

cross blood brain barrier and treat brain tumors

[image]

BB king can blow his lungs out

Bleomycin (generates free radicals and intercalates DNA)

Busulfan (alkylating agent)

(vinka alkaloid)

M phase specific

Microtuble polymerization blockers

Mitotic spindle cannot form

used for: Hodgkin lymphoma

Wilms Tumor

Choriocarcinoma

SE:

Vincristine: neurotoxic

Vinblastine: blasts bone marrow

M phase specific

stabalizes polymerization of microtubules

mitotic spindle can't break down

anaphase can't occur

use: ovarian and breast cancer

SE: HSR

PC VAG don't like micro anything! lol..

Paclitaxel (Taxanes)

Colchicine

Vinca drugs (Vincristine and Vinblastine)

Antihelminthic drugs (bendazoles)

Griseofulvin

Alkylating agent

[image]

cross links DNA& RNA strands

Genitourinary cancers:

Testicular Cancer

Ovarian Cancer

Bladder Cancer

Lung carcinoma

__________________________

SE: Nephrotoxic and Ototoxic

How can prednisone be used to treat cancer?

What are the side effects?

Prednisone triggers apoptosis in many cells

SE: Cushings, Acne, Cataracts, Osteopersosis, HTN, Peptic Ulcer, Hyperglycemia/DM, Psychosis, Insomnia

Tamoxifen and Raloxifen

Selective Estrogen Receptor Antagonists in Breast and Agonists in the bone

use: ER+ breast cancer

prevention of osteopersosis

Tamoxifen (can increase risk of endometrial carcinoma for agonist effect on endometrium)

Raloxifen (safe for a woman with endometrium)

Monoclonal antibody against HER2

kills breast cancer cells that overexpress HER2

Cardiotoxic

[image]

"Betrayed HER Trast (trust) 2 and broke her heart"

enzyme inhibitor

targets mutant bcr-abl tyrosine kinase due to Philadephia chromosome

CML commonly

GI stromal tumors

[image]

REVERSIBLY  inhibit COX 1 and COX 2

side effects of ibuprofen: interstitial nephritis, GI bleeding

Naproxen. Ibuprofen.Indomethacin. Sulindac. ect..

irreversibly inhibits COX 2

used to treat RA, OA and other etiologies of acute pain

reduce colonic polyps in pts with FAP

SE: interstitial nephritis, sulfa allergic rxn, increased risk of thrombosis (stroke, MI)

REMEMBER: ASA irreversibly inhibts both COX 1 and COX2

Isoniazid

inhibits synthesis of mycolic acids

SE: drug induced lupus, peripheral neuropathy (must give B6/Pyroxidine with it to prevent this)

acts as a competitive inhibitor of tyrosine kinase enzymes in abl, c-kit and PDGF-R to decrease activation of these genes

chemotherapeutic agent for CML, GISTs and brain tumors

hepatic congestion

bud-chiari syndrome

anencephaly

spina bifida

omphalocele

gastroschisis

Gomerulus:

IF shows granular pattern of immune complex deposition

LM shows diffuse capillary thickening

IF of glomerulus shows granular patern of immune complex deposition

LM shows hypercellular glomeruli

VACUM TH(the)  BR (bedroom)

Vibrio cholera

Acne

Chlamydia

Ureaplasma Urealyticul

Mycoplasma pneumonia

Tularemia

H.Pylori

Borrelia burgdorfi

Rickettsiae Rickettsii

PUS

atypical Pneumonia (Legionella, mycoplasma, chlamydia)

URIs (Group A strep also)

STDs (Gonnorrhea and Chlamydia)

HENS PEK

Haemophilus influenzae

Eneterobacter

Neisseria

Serratia

Proteus Mirabilis

E.Coli

Klebsiella

gram + cocci too

Legionella pneumophila

also army barracks

increased opening pressure

decreased glucose

increased protein

increased neutrophils

(fungus is the same EXCEPT increased lymphocytes  instead of neutrophils , TB looks funcal with increased lymphocytes)

How does Thyroid hormone increase BMR?

How does thyroid hormone increase sympathetic nervous system activity?

BMR: Increases synthesis of Na-K ATPase

_____________________________________

Sympathetic Nervous System activity: Beta 1 adrenergic receptors

Because fibroblasts behind the eye and over the shin have TSH receptors and secrete excess GAGs when stimulated

What would you expect to see in the serum in a pt with Graves disease?

INCREASED total and free T4

decreased TSH

hypocholesterolemia

HYPERGLYCEMIA

What is the treatment for hyperthyroidism?

Explain each

Beta blockers:blocks the beta 1 adrenergic stimulation by thyroid hormone

Thioamide: blocks peroxidase which is necessary for oxidation, organification and coupling to produced T3 and T4

Radioiodine ablation: destroy thyroid cells by taking up radioiodine

PTU: inhibits peroxidase mediated oxidation, organification and coupling and the peripheral conversion of T4 to T3

Beta blockers

Steroids

enlarged thyroid gland with multiple nodules du to relative iodine deficiency

if thyroid gland becomes TSH-independent, a toxic goiter will result and begin secreting excess Thyroid hormone on its own

HLA-DR5

autoimmune destruction of thryoid gland

may present as hyperthyroidism and eventually progress to hypothyroidism

chronic inflammation with formation of Germinal centers

increased risk for B cell lymphoma

Subacute (deQuervain) Granulomatous thyroiditis

presents as transient hyperthyroidism

Reidel's Fibrosing Thyroiditis

presents as hypothyroidism

classically a young female

may extend to local structures, especially the airway

adenoma or carcinoma of the thyroid

need to do biopsy with Fine Needle Aspiration

Papillary(80%) exposure to ionizing radiation in childhood major risk, nuclear grooves, nuclear clearing (orphan annie), psammomma bodies, spreads to cervical nodes, excellent prognosis

[image]

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Follicular: tumor of follicles, surrounded by fibrous capsule with invasion through the capsule

FNA can't distinguish between folicular adenoma or carcinoma, likes to spread hematogenously (blood)

[image]

Medullary:malignant proliferation of C cells, high levels of calcitonin causing hypocalcemia, calcitonin deposits as amyloid stroma

Assoc. w/MEN2A and MEN2B mutations on RET oncogene (warrants prophylactic thyroidectomy)

[image]

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Anaplastic: undifferentiated malignant tumor of thyroid, classically in elderly, invasive to local structures and can cause dysphagia or respiratory compromise, poor prognosis

Chief cells of the parathyroid

regulates free ionized calcium (unbound)

• Increase bone osteoblasts which in turn activate  osteoclast activity (releasing calcium and phosphate into blood)

• Increase small bowel absorption of calcium and phosphate

• Increase renal reabsorption of calcium and Decrease phosphate reabsorption

Nephrolithiasis: kidney stones (calcium oxalate)

Nephrocalcinosis: deposition of calcium in the tubules-->renal insufficiecny and polyuria

CNS disturbances: seizures

Constipation, peptic ulcer disease and acute pancreatitis: calcium is an enzyme activator

Osteitis fibrosa cystica: massive resorption of bone-->fibrosis and cysts in the bone

↑PTH

↑Ca

↓Phosphate

↑cAMP

(PTH binds Gs receptor and activates adenylate cyclase)

↑alkphos

(enzyme that generates alkaline environment required to lay down bone, and PTH activates osteoblasts first which turns on osteoclasts and causes resoprtion of bone)

What is the most common cause of secondary hyperparathyroidism?

why?

what will the labs for PTH, Ca, Phosphate and alkphos be?

Chronic Renal failure

With reanl failure, there is a decrease in phosphate excretion leading to an increase in serum phosphate which binds free calcium

this decrease in free calcium signals all four PTH glands to secrete PTH leading to bone resorption

↑PTH

↓serum calcium (all bound to the phosphate)

↑serum phosphate

↑alkphos

numbness and tingling (especially perioral)

muscle spasms

↓PTH and ↓calcium

T&C sign (Trousseau and Chovetsky)

end organ resistance

serum will show HIGH PTH

AD mutation associated with short stature and short 4th and 5th digits where there is a defect in Gs receptor that PTH binds

Beta cells lie in the center of the islets

[image]

A person with Type I diabetes expreiences some kind of stress (infection ex.) which causes an increase in epinephrine

Epinephrin increases the release of glucagon

Glucagon increases lipolysis leading to increased FFAs

FFAs are converted by the liver into ketone bodies

causing:

Kussmaul breathing

hyperglycemia

anion gap metabolic acidosis

hyperkalemia

(insulin drives potassium into cells but they don;t have insuline, and during acidosis H goes into cells and K comes out in order to try and buffer the blood. It will eventurally be lost in the urine resulting in hypokalemia later on)

Tx: Fluids, Insulin, Eletrolytes (potassium is important  for reasons explained earlier)

Schwann cells (aldose reductase converts sugar to sorbitol-->peripheral neuropathy

Pericytes of retinal blood vessels(aldose reductase turns sugar to sorbitol-->osmotic damage andto pericytes-->aneurysm-->rupture-->blindness)

Lens (aldose reductase converts sugar into sorbitol-->cataracts)

3 Ps

Pancreatic Endocrine Tumors

Parathyroid hyperplasia

Pituitary Adenoma

Achlorhydria (inhibits gastrin)

Cholelithiasis (inhibits CCK which contracts the gall bladder so no bile and risk for stones)

Steatorrhea (inhibits CCK)

excessive VIP

watery diarrhea

hypokalemia

achlorhydria (inhibits gastric acid secretion)

How does excess cortisol lead to HTN?

How does it cause immune suppression?

HTN: cortisol is essential for life bc it upregulates al[ha1 receptors on arterioles to maintain vascular tone. This increases the effect of NE on arterioles

Immune suppression: cortisol inhibits:

-PLA2( arachadonic acid metabolites)

-IL-2 (T cell growth factor)

-Histamine release from mast cells (important for vasodilation and vascular permeability)

Exogenous corticosteroids

Primary adrenal adenoma

(the smaller adrenal is being turned off by the lack of ACTH from the pituitary gland being turned off. The large adrenal has the tumor)

To determine the origin of the excess ACTH between a pituitary adenoma and a paraneoplastic ectopic production

Pituitary adenoma WILL RESPOND to high dose dexamethasone and cortisol levels will decrease

Paraneoplastic ectopic (small cell lung cancer) will not

Phenoxybenzamine

(nonselective irreversible alpha antagonist)

because as the tumor is removed, E and NE and can sqeezed out and kill the patient

the bladder

MEN2A MEN2B

VHL disease (AD loss of tumor suppressor gene)

NF type 1

Sun damage, albinism, xeroderma pigmentosum

Immunosuppressive therapy

Arsenic poisoning

Chronic inflammation

likes the lower lip

(bunch of B.S.

B-upper lip BCC

S-lower lip SCC)

PAH

C (x) / C (inulin) > 1.0

• C (x) > GFR
• interpretation
  • substance X is freely filtered across glomerular capillaries and is secreted from peritubular capillaries into tubular lumen
    • net tubular secretion of substance X
    • e.g., para-aminohippuric acid (PAH)

Noncompetitive

Irreversible

regulatory site

Vmax down (1/vmax do opposite)

efficacy down

Comeptitive

reversible (just add more substrate)

active site

Km

Km goes up (curve shifts to the right)

(affinity)potency goes down

What parasympathetic receptor is at the NMJ and Ganglia?

What is the second messenger?

Nicotinic

(others are muscarinc (most))

• Epi + α-blocker 
  • before non selective α-blocker is given, epi's net effect is to increase heart rate, contractility, and vasoconstriction leading a net pressor effect on blood pressure
  • after α-blocker is given, Epi α response is blocked while its β₂ response remains leading to net depressor effect on blood pressure (top of image)
• Epi + β-blocker 
  
  • before non selective α-blocker is given, epi's net effect is to increase heart rate, contractility, and vasoconstriction leading a net pressor effect on blood pressure
  • after β-blocker given, epi β response is blocked, while α response remains leading to net pressor effect (bottom of image)
• Phenylephrine + α-blocker 
  • phenylephrine (α₁ > α₂ agonist) leads to a net pressor effect on blood pressure
  • administration of a non selective α-blocker leads a net zero effect on blood pressure