-Episodic abdominal pain, cramping, and diarrhea
-Occasional hematochezia (blood in the stool)

-Extraintestinal manifestations including inflammation of the joints, eyes, and skin
 

CD...what kind of inheritance?

What kind of Dz?

Fistulas?

What gene may have polymorphism?

What Ethnic Group is at increased risk?

Multifactorial

Autoimmune

Yes

NOD2 gene

Ashkenazi Jewish...2-4 fold increase

T/F...CD shows substantial familial clustering and increased concordance rates in monozygotic twins,

T/F...They follow a mendelian inheritance pattern and are therefore classified as multifactorial.

True

False...they do not..this is why they are multifactorial

CD:  heterozygotes have a ______fold increased risk, whereas homozygotes or compound heterozygotes have a _____fold increased risk.

Are the NOD2 variants enought o cause CD?

1.5- to 4-

15- to 40-fold

No...just increase risk (contribute for 20% of genetic contribution of CD in white folks)

What are two other gene segments that may be involved in genetic inheritance of CD?

T/F....The three NOD2 variants alter the ability of monocytes in the intestinal wall to respond to resident bacteria

 ATG16L1 and IRGM

True

T/F...fiber intakes should be increased in CD?

What Vits might we need to supplement?

Surgery to remove diseased bowel, to drain abscesses, and to close fistulous tracks is often necessary.
 

False...it is poorly digested and shouldn't be

Folate, iron, calcium, and vitamin B12 commonly need to be supplemented.

True

Only a __% concordance rate between Monozygotic Twins in CD

Familial Adenomatous Polyposis (FAP)

T/F...FAP folks have 10's to 1000's of polyps in their colon?

Won't develop into CA?

What is its inheritance pattern?

What gene mutation leads to FAP?

True

False...so many that a mutation is possible...maybe multiple CA

Autosomal Dominant

Mutation in the Adenomatous Polyposis Coli (APC) gene
 

FAP:  At least ___% of individuals in Western populations develop a colorectal tumor

T/F...even in sporatic Dz...APC is a major player?

-What does APC usually form a complex with and can't once mutated?

50%

True (Somatic APC mutations also occur in more than 80% of sporadic colorectal tumors)

-Beta-catenin

regulates transcription,

cell adhesion,

the microtubular cytoskeleton,

cell migration,

crypt fission,

apoptosis, 

 cell proliferation

forms complexes with several different proteins including β-catenin.

T/F...you must lost both alleles of APC to have adenoma formation?

-does APC mutation alone cause CA?

What is the average time to progress from adenoma to carcinoma in the FAP individuals?

True

-No these APC deficient cells must ACQUIRE OTHER SOMATIC MUTATIONS TO PROGRESS TO CA.

23 years (93% have colon CA by age 50)(IF you know you have a APC mutation and develop a polyp yo colon is outty)

- causes cells to release stored food into the blood

- allows cells to take up glucose from the blood

- slows glucose absorption in small intestine; suppresses glucagon secretion
 

 -decreases GI activity; suppresses glucagon and insulin secretion

-Glucagon:

-Insulin:

-Amylin:

-Somatostatin:

Makes what?

-Alpha

-Beta (2)

-Delta

-PP cells

Glucagon

Insunlin and Amylin

Somatostatin

Pancreatic Polypeptide

Acute Pancreatitis

Common Causes (3)

Rare Causes (4 mentioned)

Alcohol

Bile stones

Unknown

Surgery

Drugs

Metabolic Dz

Infections (Mumps)

These are all features and complications of what?

Fat necrosis, calcifications, hypocalcemia
Ascites, sterile peritonitis
Shock
Massive necrosis—pseudocyst
Abscess formation
Chronic pancreatitis
Diabetes mellitus
 

Acute Pancreatitis

Chronic alcoholism (70%)
Trauma
Systemic metabolic or endocrine disease
Unknown (20%)

THese are clinical features of what?

 Insidious onset
Pain in upper abdomen that radiates into the back
Malabsorption caused by pancreatic insufficiency
X-ray evidence of calcifications
Secondary diabetes mellitus

-What is this called:  Activated enzymes begin to digest the pancreas cells.  Severe pain results.  Inflammation produces large volumes of serous exudate  hypovolemia

-What enzymes would we look for IN THE BLOOD to Dx (2)?

-What deposits in the dead pancreatic cells that have undergone fat necrosis?

Autodigestion of the Pancreas

Amylase and Lipase

Calcium(causes systemic Hypocalemia)

-T/F...chronic pancreatitis and pancreatic CA

have signs and symptoms similar to acute pancreatitis

-What two things increase your chances of developing Pancreatic CA?

-95% of Pancreatic Tumors are ENDOCRINE tumors?

-True

-Smoking and past hx of Chronic pancreatitis

-False...they are exocrine tumors

-If pancreatic CA is in head what will result?

-T/F...most pancreatic CA occurs at teh duct level and is cystic in consistency

-Jaundice

-False, Occurs at teh duct but is Solid in consistency

What part of the pancreas can give you severe pain if a carcinoma develops there?

T/F...jaundice is a common symptom of Pancreatic carcinomas?

T/F...Islets of Langerhans are lost early on in chronic pancreatitis

-The Tail

-True

-False, they are mostly preserved....but in late stages of disease, reduced in number of replaced by fibrous tissue
 

Type 1 or 2 DM?

Higher Twin Concordance?

Antibodies to Islet Cells?

Normal Serum Insulin Levels?

Tx with Diet, oral hypoglycemics, and sometimes insulin?

II

I

II

II

-What is Drop foot an example of for DM?

Are nerve cells hyper or hypo osmolar to the blood?

What happens as a result?

Any other issues with these nerve cells?

-Peripheral Neuropathy (Somatic)

Hyperosmolar

Swelling of the cell...

vascular dz secondary to DM can lead to lack of Oxygen and demylination of the nerve cells

What organ am I?...Carbohydrate, protein, and lipid metabolism

Drug and hormone metabolism
Biotransformation into _______-______ forms.

T/F...Anemia may result from Liver failure?

T/F...Hyperkalemia may result from Liver Failure?

-The Liver

-water-soluble

-True

False, Hypokalemia may result

-T/F...Asterixis, confusion, coma, convulsions may result from Liver failure

-T/F...Leukocytopenia may result from failure?

-What are 3 complications of Portal HTN?

-What 3 things result from an ANASTOMOSES of Portal and systemic circulation?

True

True (a result of splenomegaly)

-Ascites, Splenomegaly, and Anastomoses

-Hemorrhoids, Esophageal Varices, Caput Medusae (ascites)

-What causes most prehepatic Jaundices?

-What 4 things cause hepatic Jaundice?

-Name some causes of posthepatic Jaundice?

-Hemolysis

-Viral, Drugs, Cirrhosis, Tumors

- Gallstones in bile duct, tumors in pancreas, etc....

-When bile ducts rupture and damage liver cells
_____  _____ is released into blood

-What causes pruritis that is associated with Biliary disorders?

-Excess bilirubin in teh blood leads to what?

-What does bilirubin eventually become normally in the liver?

Alkaline phosphatase

Increased bile acids in blood and skin

Jaundice yo

Bile

-What are the 3 autoimmune disorders that may cause Cirrhosis?

-What are 3 hereditary metabolic Dz's

What are the causes of Cryptogenic Cirrhosis?

-primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis

-Wilson’s disease, hemochromatosis, alpha1-antitrypsin deficiency

-We don't know...so stop askin.

Immune Dz:

 T/F...Autoimmune hepatitis affects mainly men?

-Primary biliary cirrhosis (PBC) characterized by destruction of intrapeatic bile ducts and progression to cirrhosis (usually in Women).  

-What group is usually affected by Primary Schlerosis cholangitis?

-False, Women (they will have large amounts of antibodies to smooth muscle (ASM).

-True (probably T-cell related as it isn't suppurative)(destruction of bile duct)

-Men under 40...also those with UC. (constriction of bile duct)

What 2 things make up Gallstones?

-what is Choledocholithiasis

 

-cholesterol, calcium salts or a mixture of these

-Stones in the common bile duct

Hereditary Liver Dz...:

-benign recurrent jaundice with unconjugated bilirubin

 -excessive accumulation of iron in many organs, cirrhosis

 -excessive accumulation of copper (liver, eye, central nervous system), cirrhosis

-accumulation of AAT, cirrhosis

- Gilbert's Dz

- Hemochromatosis

-Wilson's Dz

- Alpha1-antitrypsin deficiency

-Mutations of what make Breast CA more likely?

-what do these genes code for?

-What hormone overload leads to Breast CA?

-Mutation of BRCA1 or BRCA2 make cancer more likely

-BRCA1 and BRCA2 genes code for proteins that help repair DNA after it has mutated

-Estrogen and other growth factors make breast cells divide.  Breast cells with too many estrogen or growth factor receptors are more likely to become cancerous
 

Fribromas

Found in who?

Composed of?

How do we Tx?

-Found in young women 15 to 35 years of age

-Composed of fibrous stroma and glandular epithelium

-Easily removed surgically—does not recur and does not become malignant
 

-In __% there is no known family hx of breast CA

-  If a women participates in daily activity her chances of death go down __%

-What race is more commonly affected?

-What gender more commoly affected>?

-80%

-50%

-Caucasians

-FEMALES

-What node gets metastasized most often?

-The younger teh female the ____ chance teh tumor is benign?

-Axillary (45%)

- higer

-

Males hormones:

-Who releases FSH?

-Who Relases LH?

-What does the Hypothalmus release?

-What does LH do?

-What does testosterone do? 

What does FSH do?

-Ant Pit

-Ant Pit

-GnRh (stimulates LH and FSH production)

-Stimullates Interstitial cells (Leydig's to make TESTOSTERONE ...they also make Androgen)

-Testosterone is responsible for stimulating spermatogenesis (ALONG WITH FSH) AND producing secondary sexual characteristics

-What 2 tubules pass through Male Prostate?

-_____ initiatiates sperm formation by producing GnRH to activiate the _____.

-Pituitary produces what two hormones?

-Sertoli cells responsible for?

-Interstitial Cells of Leydig responsible for ______ production?

-T/F....they both act to help in sperm maturation

-Ejaculatory Duct and Urethra

-Hypothalamus/Pituitary(ANTERIOR)

-LH(Interstitial cells of Leydig) and FSH (acts on Sertoli Cells)

-  Spermatogenesis

-Testosterone (neg feedback)

-True

-about __% of premature infants will have undescended testes...(surgical tx required)

-E.coli causes what 2 organs to be infected?

-Where does the mumps virus attack?

-Where does Gonorrheaa attack?

-Where does Herpes attack?

- Herpes or syphillis....(AN ULCER)

-30% (60% cryptos stuck in high scrotum)

-Bladder/Prostate

- Testes

-Urethra

- Glands/penis

-Syphillis

-________ is a worldwide STI that is successfully treated with

-Where does syphillis like to hang out?

-Gonorrhea

-Dorsal Column of Spinal cord (where proprioception info is transmitted...these people will walk very funnily as degeneration progresses)

-What age group is affected by testicular CA

-Most tumors are of what origin?

-T/F....most of these tumors are malignant and will render the individual infertile post-op

-Prognosis is good?

-25-45 yo

-Germ cell

-True

-Yes 90% will survive

-Where do metastases of testicular CA go (3 places)?

-Where on the prostate do Carcinomas commonly arise?

-Can a alteration in prostate cause discharge?

-Decreasing what hormone can decrease BPH?

-Prostate, Kidney, Large intestine

- Posterior

-Yes

-Testosterone

-What is the most common internal CA of Males?

-What race is more commonly affected?

-What is our marker for prostate CA?

-True/False...bone metastases of prostate CA are always osteolytic.

-Prostate CA

-African-American Men

-PSA (prostate specific antigen) 

-False...both osteolytic and osteoblastic

-What helps reduce teh risk of Penile CA?

-What types of cells are affected usually?

-where does it usually metastasize to?

-Circumcision

-Squamous Cell Carcinomas

-Inguinal Lymph Nodes

-What is a common penile disorder that results in a bent penis?

-This can go away with time?

- Where does the Hypospadias come out?

-Where does Epispadias come out?

-Peyronie Dz

-Yes ...but is very painful for male to have an erection

-along Urethra

-Above...superior to normal urethral meatus

-Most Ovarian Neoplasms occur wehre?

-what are some good screening tests for OVARIAN CA?

-Where do most Ectopic Pregnancies occur?

-What is the diff between PREeclampsia and Eclampsia?

-Surface Epithelium-

-There are none (most metastasize before they are discovered)

-In the fallopian tube (95%)

-Those with Eclampsia have the same Sx as those with PREeclampsia plus SEIZURES

PID in Women causes inflammation which leads to what signs/symptoms (4)

Pain in lower abdomen and cervix

Purulent discharge

Increased WBC count

Increased C-reactive protein

-T/F...Pregnant women frequently have urinary leakage?

-What does estrogen do to bones?

-Does it affect fluids and tissues?

-Also important for cell division in what 2 organs?

-True

-Decreases bone resorption (breakdown)

-Yes helps force fluid into tissues 

-Breasts and Endometrium

 What hormone is necessary for maintaining pregnancy?

-its role for smooth muscles

-for temperature

-for endometrail cells?

 -Progesterone

-smooth muscle relaxation

-Increases body temperature

-maintanence of endometrial Cell

What hormone is related to Endometrial Adenocarcinoma when it is toohigh for too long?

-T/F most endometrial tumors are benign?

-What is this?:  is a benign smooth muscle neoplasm that is not premalignant. They can occur in any organ, but the most common forms occur in the uterus, small intestine and the esophagus
Leiomyosarcoma (malignant, rare)
 

-Estrogen (combined with insuficient levels of progesterone)

-False, all endometrial tumors are MALIGNANT

-Leiomyoma (benign, common)

What 2 hormones peak at 14 days?

-what is this correlated with?

-When does ESTROGEN peak

-What does this correlate with?

-LH and FSH

-Ovulation

-10 or so days

-Proliferative phase (decreased FSH release)

 -Why is ovarian CA such an insidious dz for women?

-Where does gonnorrhea attack in females?

-Where does Trichomonas attack?

-There really are no signs and symptoms (you may mistake it for menopause)

-Cervix

- Vagina (Vaginitis)

-Is pH of vaginia acidic or basic?

-Acidic (3.4-4.2)

 In younger women:

-Vulvular CA often preceded by vulvar ________ ______.

-what virus is it related to?

Stopped here........

-intraepithelial neoplasia

-HPV

Hormones: In women...

-What hormone stimulates ovulation?

-What hormone stimulates Follicle development?

-What hormone does this developing follicle start producing?

-What hormone(s) does the Corpus Luteum produce?

-Which hormon prepares endometrium for implantation?

-LH

-FSH

-Estrogen

-Progesterone and Estrogen

-Progesterone

What 2 hormones make Breast CA more likely?

-Do Fibroadenomas usually become Malignant?

-Estrogen and Growth factors

-They don't (pk risk age 15-35 yo 2-5cm)

-T/F...The X and Y chromoxomes are inherited with unique patterns?

-They pair in female mitosis?

-What are the 3 levels at which sex is determined?

True

-False, they pair in MALE MITOSIS despite their differences

-Chromosomal, Gonadal and Phenotypic

Embryo: Sexual differentiation begins at week _?

-What is teh sex-determining region of the Y chrom?

-What is the name of this hormone: Hormone produced by developing testis that causes breakdown of the paramesonephric ducts (formerly called Müllerian ducts) in the embryo; the female ducts
 

-Week 8

-SRY gene

-Anti-Mullerian Hormone

-What hormone is this:  Stimulates development of the mesonephric ducts (formerly called Wolffian ducts) in the embryo; the male ducts

 -Mutations in  __-linked and ______ genes can uncouple chromosomal sex from phenotypic sex and lead to sex reversal, ambiguous genitalia or even complete gonadal dysgenesis.
 

-Testosterone

-X-linked and Autosomal

-an individual with both ovarian and testicular tissue

 - an individual with a 46,XX karyotype and normal ovarian tissue, but with ambiguous or male external genitalia

 - an individual with a 46,XY karyotype and normal testicular tissue, but with ambiguous or female external genitalia
 

-Hermaphrodite

-Female pseudohermaphrodite

-Male pseudohermaphrodite

What is this: an inherited autosomal recessive disorder of hormone synthesis by the adrenal glands that leads to female pseudohermism?

-What gene is mutated in this disorder?

-What 2 hormones are needed to keep the body from producing ANDROGEN?

-CAH (congenital adrenal hyperplasia)

-CYP21A2 (gene that causes a lack of enzyme 21-hydroxylase...this enzyme is needed by adrenal gland to produce cortisol and aldosterone)

-Cortisol and aldosterone

What happens to male infants with CAH?

What can cause Male Pseudohermaphroditism?

-Nothing they will have normal external genitalia

-Lots of things...disorders of testes development, abnormalities of gonadotropins, inherited disorders of testosterone biosyn/metabolism, abnormalities of androgen target cells

-What is the expressed on the X chromosome that is to be silenced?

-T/F...this serves to silence ALL genes on the inactive X chromosome?

-What does this Inactive chromosome become?

-XIST RNA located in the Xic (X inactivation center) region of that chromosome

-False...not all genes are silenced

-Barr Body

T/F...In females, some cells express the mother’s X chromosome and some cells express the father’s X chromosome

-Can Inactivated X chromosome switch once it is set for a particular Somatic line?

True...Females are Mosaics

-No, Inactivation is permanent; all descendants of a particular cell have the same X inactivated
 

-The phenotypes associated with sex chromosome defects are, in general, more severe than those associated with comparable autosomal disorders

-T/F...The Y Chromosome is not necessary for Survival.

-False, they are less severe due to X chromosome inactivation

-True

-What is the Aneuploidy in Klinefelter's Syndrome?

-Common?

-47,XXY karyotype due to nondisjunction; some have additional X chromosomes.

-Yes 1 in 500 to 1,000 male live births

Klinefelter Syndrome

-Individuals with ___ have a male phenotype and are fertile. They tend to have learning disabilities and behavioral problems. Many have relatively tall stature.

-Since these individuals are FERTILE...how common is XXY or XYY inheritance?

-  XYY

-VERY RARE

-XXX, Trisomy X

-Turner SYndrome

-XYY Sydrome

-XYY Syndrome

-T/F....Breast cancer is the second leading cause of cancer death in women between the ages of 15 and 54

-What are some risk factors for Breast CA?

-False...IT IS THE LEADING CAUSE OF DEATH (12% of women will get breast CA in their lifetime)

A woman’s risk for development of breast cancer is increased up to ____ if one first-degree relative is affected

-What are the 2 gene mutations that contribute to Breast and Ovarian CA?

-What kind of Inheritance is this?

-3-fold

-BRCA1 and BRCA2

-AUTOSOMAL DOMINANT

-What kinds of genes are BRCA1 and BRCA2?

-What kind of mechanism is thought necessary to cause breast CA with these genes?

-Mutations in these genes cause what % of Familial Breast CA?

-TSGs (tumor suppresor genes)

-Two-hit hypothesis

-70-80%

-What allele may play a role in IDDM?

-What is the earliest sign of IDDM?

-What do 50% of IDDM pts die of?

-T/F...The administration of insulin or nicotinamide appears to delay the development of IDDM in some patients.
 

-DQB1*602 (a protective allele)

- the development of islet autoantibodies

-Renal Failure

-True in those whos islet autoantibodies have been detected.

 -Is it better to have an infected father or mother when it comes to reducing your chances of inheritance of IDDM?

-What percent of NIDDM acquired it genetically?

-Which Gene is involved in NIDDM?

-what does this gene do?

-Mother has a lesser chance of passing dz to child.

- 10%

-TCF7L2

-Transcription factor for GLUCAGON which acts to increase bloodglucose levels.

-what polymorphism is involved with NIDDM in the Finnish and Mexican American populations?

-Which group has Acanthosis nigricans?

-T/F...? The population risk of NIDDM is highly dependent on the population under consideration; 

-PPARG:  PPARG encodes a member of the nuclear hormone receptor family and is important in the regulation of adipocyte function and differentiation.

-NIDDM

-True