SLE

MCTD
ELASTIN
Elastin

Has many GLYCINES

Has PROLINES
Has LYSINES
Has OH-PROLINES
NO hydroxylysines

287 275
15
Elastin
Provides COMPLIANCE
Provides ELASTICITY
Has DESMOSINE
Elastase
Destroys elastin
Cuts to the right of GLY, ALA, and SER
Alpha-one antitrypsin inhibits elastase
Found in neutrophils and bacteria
Smoke inhibits alpha-one antitrypsin
Decreased alpha-one antitrypsin with
aging
Emphysema
Destruction of elastin
Loss of recoil
Panacinar: alpha-one antitrypsin deficiency
Centroacinar: smoking
Disto-acinar: aging
Bullous: staph aureus and pseudomonas
Whos afraid of staph aureus and
pseudomonas?
Neutropenic
Burn patients
Cystic fibrosis
Diabetics
If any fever, cover staph aureus with one
antibiotic and cover pseudomonas with
two antibiotics
Keratin
Made for tensile strength
Contains a lot of CYSTEINES THE END

ONLY FOR NOW

288 276
1
ENZYMES
THE MOST IMPORTANT
PROTEINS IN YOUR BODY
IF asked whether a reaction is
possible
THE answer is always YES!
ANYTHING, as we know
IS POSSIBLE!!
A Reaction
An Enzyme
Brings substrates together in space and
time
Lowers the free Energy of activation
Stabilizes the hi energy intermediate
Is not consumed in the reaction
An ENZYME has
289 277
2
Competitive inhibition
Inhibitor is similar to the substrate
The inhibitor is competing for the active
site
Affinity I decreased
Km increases
Vmax remains the same ( just add more
substrate)
reversible
Noncompetitive inhibition

NOT similar to the substrate

Does NOT bind active site
Binds to regulatory site
Turns off the enzyme
Km remains the same
Vmax decreases
irreversible

What makes a reaction favorable

and spontaneous

Effects of temperature on a
reaction
E
REDOX POTENTIAL
E
You want it to be negative
When negative: has electrons
to give
When positive: wants to accept
electrons
290 278
3
Reducing agent
Has a negative delta E
Wants to give away electrons
Gets oxidized after the reaction
Oxidizing agent
Has a positive delta E
Wants to accept electrons
Gets reduced after the reaction
Electron Transport System
Inhibitors and Uncouplers
291 279
4
Inhibitors Uncouplers
DNP
ASPIRIN
FREE FATTY ACIDS
How to name enzymes
FIRST NAME of an enzyme
IS the name of the SUBSTRATE
LAST NAME of an enzyme
Is what you did to the substrate
LAST NAMES of enzymes
Kinase
Phosphorylase
Isomerase
Epimerase

 Mutase
Transferase
Lyase
Carboxylase
Synthase
Synthetase
Dehydrogenase
Hydrolase
292 280
5
Coming to a screen near
you
THE PATHWAYS
293 281
Anabolic Pathways:
Putting it all back together
As soon as you eat
You replenish your plasma glucose
After glucose returns to
the liver
You turn off gluconeogenesis
After you turn off
gluconeogenesis
You turn on glycogen synthesis
Glycogen Synthesis
294 282
Pentose Pathway
NADPH is used for
Fatty acid synthesis
DNA synthesis
RBC repair ( used by glutathione)
X-linked Recessive Enzymes
G6PD
Fabrys ( alpha galactosidase)
Hunters ( Iduronidase)
CGD ( NADPH Oxidase)
Lesch-Nyhan ( HGPRT)
Pyruvate Dehydrogenase
Adrenoleukodystrophy ( CAT-1)

G6PD
More common in Meditteranians ( protects
them from malaria)
Mcc of hemolytic crisis: ( 1) infection (2)
drugs
Drugs that oxidize RBCs: sulfa drugs;
antimalarials; metronidazole; INH
295 283
Amino Acid Synthesis Fatty Acid Synthesis
Palmitic Acid
The main fatty acid that we make every
day
Saturated FA: NO double bonds
Unsaturated FA: has double bonds
Omega FA: counting carbons from the right
side
Omega 3 FA: Lowers serum cholesterol
Pocosanol
Rules for Fatty Acids
We do NOT go beyond C-16
Double bonds have to be at least 3
carbons apart
NO double bonds after C-10
Essential Fatty Acids

Linolinic
Linoleic ( used to make arachadonic acid)
Come ONLY from the diet
Your body can not make these

296 284
Arachadonic Acid Irreversible Cyclo-Oxygenase Inhibitor
Aspirin
Reversible Cyclo-Oxygenase
inhibitors
NSAIDs
Indomethacin
Phenylbutazone
Ibuprofen
Naproxen
Baclofen
Ketorelac
cyclobenzaprine
Steroids
Antiinflammatory
actions
Inhibit PLP-A
Kills T-cells and

eosinophils
Inhibits macrophage
migration
Stabilizes mast cells
Stabilizes endothelium
Physiologic actions
Proteolysis
gluconeogenesis
Steroids
Prednisone
Methylprednisalone
Triamcinalone
Beclamethasone
Betamethasone
Hydrocortisone
Dexamethasone
fludrocortisone
Cypropterone
Megestrol
Fluticasone
Mometasone
Danazol
Mast Cell Stabilizers
Cromolyn
Nedacromyl
297 285
LRBs
Zifurlekast
Montelekast
Zileutin
Triglyceride Synthesis
Triglyceride Transport
Chilomicrons
VLDL
IDL
Signs:
Xanthelesma
Pancreatitis
Sphyngolipids
Lysosomal Storage Diseases
Gaucher: glucocerebrosidase
Fabrys: alpha galactosidase
Krabbes: beta galactocerebrosidase
Tay Sacks: hexoseaminidase A
Sandhoffs: hexoseaminidase A & B

 Nieman Pick: sphyngomylinase

Metachromatic leukodystrophy: arylsulphatase
Hurlers: iduronidase
Hunters: iduronidase sulphatase
And Now
The final anabolic
process
298 286
Cholesterol Synthesis NUCLEOTIDES
NUCLEOTIDES
RNA
DNA
ENERGY
CARRIERS ( UDP & CDP)
METHYL GROUP CARRIER ( S-AM)
SECOND MESSENGERS
PURINES
Adenine
Guanine
PYRIMIDINES
Thymidine
Cytidine
Uracil
NUCLEOTIDES
299 287
THE BLOTS
Southern blot: DNA
Northern blot: RNA
Western blot: PROTEIN
PCR: amplifies DNA or RNA
ELIZA
EUCHROMATIN
Loose DNA; has more A and T
HETEROCHROMATIN
Tight DNA; has more G and C
PURINES
PYRIMIDINES
RIBONUCLEOTIDE REDUCTASE
300 288
SCID

 Adenosine deaminase def

Unable to make DNA
Affects all rapidly dividing cells, especially
bone marrow
Bone marrow transplant is now current
therapy
The DNA Helix
HISTONES
Help bind DNA helix
H-1
H-2a
H-2b
H-3
H-4
Basic
Anti-Histone Antibody
Hydralazine
INH
Procainamide
Penicillamine
Phenytoin
Ethusuximide
CELLULAR CYCLE DNA REPLICATION
301 289
TRANSCRIPTION TRANSLATION
DIFFERENCES
DNA Replication
DNA POL alpha
DNA POL beta
DNA POL gamma
DNA POL delta
DNA POL epsilon
Replication forks
Transcription
Monocistronic
polycistronic
Translation
Fmet vs met
MUTATIONS
Frameshift mutations
Point mutations
Transition mutations
Transversion mutations
Silent mutations
Missence mutations
Nonsence mutations
CAN IT BE ?
YES, IT IS!!!

IT IS THE END
302 290
OR IS IT.
303 291
Catabolic Pathways
Breaking it all down
Sources of Energy
Glucose ( 40% of diet)
Proteins ( 30% of diet)
Fats ( 30% of diet)
Ketones ( last resort)
Breaking Down Sugars First
Breaking Down Sugars
Begins With Glycolysis
RBC Connection
RBCs use ONLY glucose for energy
Hypoglycemia will ALWAYS affect RBCs
first, causing a hemolytic anemia
The only other pathway RBCs have is the
pentose pathway for making NADPH to
maintain the membrane
304 292
Glycolysis
Glycolysis
The most active pathway in your body
CATABOLIC in all cells except the liver
where it is ANABOLIC
CATABOLIC STATE
Is controlled by the sympathetic system
Second messenger is C-amp
Is controlled hormonally by epinephrine
and glucagon
How to use energy
305 293
DHAP
Used in the glycerol 3 phosphate shuttle
Used in triglyceride synthesis
Glyceraldehyde 3 phosphate

dehydrogenase
Has sulphur in the active site
Is blocked by mercury poisoning
Mercury Toxicity
Mcc: (1) Tuna (2) a child biting into a
thermometer
Blocks glyceraldehyde 3 phosphate
dehydrogenase
LOW ENERGY STATE
RBCs affected first
Brain affected the most
Pallegra
Niacin deficiency
The 4 Ds
Dermatitis
Diarrhea
Dimentia
Death
Hartnups: presents just like pallegra.
Defective renal transport of tryptophan
306 294
Flouride Poisoning
Blocks the enzyme ENOLASE
Caused in the past by eating rocks of
flouride
Rare today since flouride added to water
and toothpaste
Clue: extra white teeth and bones
Gluconeogenesis
Gluconeogenesis
Controlled by epinephrine and glucagon
Second messenger is C-amp
Occurs only in the liver (90%) and the
adrenal cortex (10%)
Occurs while other tissues are running
glycolysis
Occurs in the mitochondria and cytoplasm
307 295
To reverse glycolysis

Pyruvate carboxylase ( rate limiting)

PEP Carboxykinase
F16DPase
G6Pase

Galactose Metabolism
Detecting Sugars

 In the urine: CLINITEST

In the stool: positive REDUCING SUBSTANCES
Galactosuria

Galactokinase deficiency
Hexokinase fills in for galactokinase
Galactose in the urine ( clinitest positive)
Symptoms: polyuria; polydypsia; UTIs

308 296
Galactosemia
Galactose 1 phosphate uridyltransferase
deficiency
Galactose 1 phosphate builds up in the
cells
RBCs affected first
Brain affected the most
LOW ENERGY STATE
Fructose Metabolism
Fructosuria
Fructokinase is missing
Hexokinase fills in
Fructose in the urine ( clinitest positive)
Polyuria
Polydypsia
UTIs
Fructosemia
Aldolase B is missing
Fructose 1 phosphate is trapped within the
cells and can not leave
RBCs affected first
Brain affected the most
LOW ENERGY STATE
Before you enter the KREB CYCLE
YOU NEED TO
KNOW
309 297
THE FIVE FATES OF
PYRUVATE
5 FATES OF PYRUVATE
Pyruvate Dehydrogenase
KREB CYCLE
Malate-Aspartate Shuttle Glycerol 3 Phosphate Shuttle
310 298

Amino Acid Catabolism Fatty Acid Catabolism

Palmitic acid: C-16 the main fatty acid we
make daily
Three formulas to know:
( C/2 1) : the number of rounds it takes to
break down a fatty acid chain or the number
of rounds it took to make a fatty acid chain
( C/2 1) 2 : the number of NADPHs it cost to
make a fatty acid chain
( C - 1): the number of ATPs it cost to make it
Fatty Acid Catabolism Adrenoleukodystrophy
Defective carnitine shuttle
Long chain free fatty acids accumulate in
the cytoplasm, unable to enter
mitochondria
X-linked recessive
Adrenal gland failure
Early white matter involvement
X-linked Recessive Enzymes
G6PD
Pyruvate dehydrogenase
NADPH-Oxidase
HGPRT (Lesch-Nyhan)
Alpha-Galactosidase ( Fabrys)
Iduronidase ( Hunters)
CAT-1 (Adrenoleukodystrophy)
Beta - Oxidation
311 299
Odd numbered carbon fatty acid
metabolism Ketogenesis
IDDM ( TYPE 1 DIABETES)
Autoimmune
2 weeks after a viral
(Cocksackie B) infection
Anti-islet cell antibody
Sx begin after 90% of
islet cells are destroyed
Remaining 10% will
undergo hyperplasia
( honeymoon period)
Signs and sx: LOW
ENERGY STATE
DKA
Hypovolemia
Lack of insulin
Low body potassium
Hyperkalemia
Hypophosphatemia
Pseudohyponatremia
Correcting sodium

Visceral pain
False high creatinine
Correcting glucose
Correcting acidosis

Reasons NEVER to give bicarbonate

in treatment of DKA
It merely corrects a number without
correcting the actual problem
Decreased cardiac output
Causes hypokalemia
Shifts hemoglobin dissociation curve to the
left
Bicarbonate ion does NOT cross the blood
brain barrier ( CSF pH falls paradoxically)
NIDDM ( Type II Diabetes)
Genetic
Connected to obesity
Downregulation of
insulin receptors
Hyperinsulinemia
Nonketotic
Hyperglycemic,
nonketotic coma
Complications
Vasculitis
Clots
Bleeds
Nephropathy
Neuropathy
IDM
Tx: weight loss
Meds
insulin
Sulfonylureas
Chlorpropamide
Tolbutamide
Tolezalide
Glipizide
Glyburide
312 300
Other Oral Hypoglycemics
Ascarbose
Miglitol
Metformin

Piaglitazone
Rotiglitazone
Repaglinide
Troglitazone

Insulins
Dawn effect
Increase in blood sugar each morning
caused by the normal increase in
epinephrine, glucagon and cortisol that
occurs each morning
Tx: increase morning regular insulin
Somoji effect
Actually caused by HYPOGLYCEMIA that
occurred in the early morning ( 2 to 3 am)
leading to reactive HYPERGLYCEMIA in
the late morning ( 6 to 7 am)
Tx: decrease evening NPH insulin
Glycogen: Synthesis / Catabolism Glycogen: Synthesis / Catabolism
313 301
Glycogen: Synthesis / Catabolism Glycogen: Synthesis / Catabolism
Glycogen: Synthesis / Catabolism Glycogen Storage Diseases
Glycogen Storage Diseases
Von Gierkes: glucose 6 phosphatase
Andersons: branching enzyme
Corys: debranching enzyme
Hers: liver phosphorylase
Mcardles: muscle phosphorylase
Pompes: cardiac alpha 1,4 glucosidase
The End of CATABOLISM
The Beginning of ANABOLIC
PATHWAYS
314 302
1
Forgiveness
Through Gods love, you always have
infinite forgiveness
Unfortunately, you dont always have
infinite time
The Physiology of CANCERS
CELLS OUT OF CONTROL
Anaplasia
Cells revert back to their mesenchymal

origin
NO MATURATION TIME NEEDED
The most aggressive type of cancer
Divides rapidly
Metastasizes early and aggressively
SENSITIVE to radiation or chemo
Metaplasia
Replacement of one adult cell type for
another
The new cell can better handle the stress
315 303
2
Desmoplasia
A collagenous reaction surrounding a
tumor
Dysplasia
Loss of cell to cell contact inhibition
Cells begin to crawl on top of each other
This is the FIRST STAGE OF CANCER
Also known as carcinoma in situ ( CIN)
Any cancer that is caught at this stage has
a good prognosis if removed ( 90% 5 year
survival)
ALL screening is done to find cancer at
this stage
NEOPLASIA
BENIGN
Well circumscribed
Freely mobile
Encapsulated
Does not outgrow
capsule
Does not outgrow
blood supply
NO METS
Obeys physio
MALIGNANT
Not circumscribed
Adherent
Not encapsulated
Outgrows capsule
Outgrows blood supply
METS
Does NOT obey
physio
Malignant Neoplasia
Angiogenin

 Endostatin
316 304
3
When you have one BILLION
cells
You can SEE the cancer with the naked
eyes
You can PALPATE it on exam
Chemo must kill at least one billion cells to
be considered effective
How long does it take for ONE
BILLION cells to reassemble?
If a cancer outgrows its blood
supply, go to the
BRAIN
LUNGS
BONE
LIVER
ADRENAL
PERICARDIUM
To Name a Tumor
First name: the most common cell type
Last name: add - oma at the end
To Name a Cancer
First name: most common cell type being
stressed
Prefix for every glandular tissue is ADENO
Last name: carcinoma if it originates from
epithelium
Sarcoma if it originates from connective tissue
TRICKY - OMAs
Hamartoma: abnormal growth of normal
tissue
Choristoma: abnormal location of normal
tissue
317 305
4
Cancers that lost their proper
endings
Hepatoma
Seminoma
Lymphoma
Teratoma
Mesothelioma
Retinoblastoma
Neuroblastoma

 Nephroblastoma ( Wilms tumor)

Let us now beginone organ at a
time
BRAIN
Most common INTRACRANIAL tumor:
MENINGIOMA
Displaces the brain
Psammoma bodies ( calcifications)
Psammoma Bodies

Papillary carcinoma of thyroid

Serous
Adenocarcinoma of the ovaries
Meningioma
Mesothelioma

BRAIN, cont
Most common primary brain tumor:
ASTROCYTOMA
GLIOMA
OLIGODENDRIGLIOMA
EPENDYMOMA
Neurocutaneous Syndromes
ALL have mental retardation, seizures and
cerebral calcifications in common
All have tumors or cancers associated with
them
All have different cutaneous findings
318 306
5
Neurofibromatosis
Caf au lait spots ( hyperpigmented
macules)
Associated with chromosome 17/22
Neuromas
Peripheral neuromas: chromosome 17(type 1)
Central neuromas: chromosome 22(type 2)
fibromas
Sturge Weber syndrome
Port wine stain on forehead
Angiomas of retina and brain
BRAIN, cont
Most common primary brain cancer:
astrocytoma grade IV or GLIOBLASTOMA
MULTIFORME

 Most common cancer: METASTASES

Usually found at the grey-white matter
junction
Pituitary
Most common tumor: pituitary ADENOMA
Cell types:
Chromophobes ( nonfunctional) 95%
Acidophils (produce PRL and GH)
Basophils ( produce ACTH, TSH, FSH and LH)
Most common FUNCTIONAL tumor:
PROLACTINOMA
Most common cancer:
ADENOCARCINOMA (rare)
Pineal
Most common tumor: pineal adenoma
( PINEALOMA)
CN VI palsy (esotropia)
Precocious puberty
Most common cancer:
ADENOCARCINOMA (rare)
Posterior Fossa Tumors
Present with early morning vomitting
Common in children

MEDULLOBLASTOMA
Cerebellar origin; it sits on top of the medulla
CRANIOPHARYNGIOMA
Develops from Rathkes pouch
Has a motor oil appearance
Has some calcifications
May damage anterior or posterior pituitary

319 307
6
Mediastinum
Anterior
Middle
Posterior
Posterior Mediastinum
Mostly ganglia located there
Most common tumor: NEUROMA
Most common cancer:
NEUROBLASTOMA
Neural Crest Cancers
NEUROBLASTOMA
Most common

abdominal mass in
children
Hypsarrythmia
Opsoclonus
Highest spontaneous
regression rate (2%)
PHEOchromocytoma
Located in adrenal
medulla
10% in children
10% bilateral
10% metastatic
10% familial
10% malignant
Neural Crest Cancers
Paroxysmal palpitations, HTN, headache
and diaphoresis
Unable to differentiate benign from
malignant histologically
Must remove ALL of them
Dx: check urinary VMA, metanephrines, or
HVA
Phentolamine
Phenoxybenzamine
Anterior Mediastinum
Thymus
Thyroid
T-cell leukemias/lymphomas
Teratomas
Thymus
Most common tumor: THYMOMA
Associated with ALL autoimmune diseases
except Graves disease
These cells are pleuripotent;
Thymus is immunopreviledged
Most common cancer:
ADENECARCINOMA (rare)
320 308
7
Thyroid
Most common mass: cyst ( throglossal)
Most common tumor: follicular adenoma
Most common cancer: papillary
carcinoma
Local metastases only
Psammoma bodies
Risk factor: previous irradiation to the neck
Thyroid Masses

CYSTIC
Thyroglossal cyst is
most common
Do ultrasound to verify
Do FNA: diagnostic
and therapeutic
SOLID
First do a thyroid scan
cold nodule and h/o
previous irradiation to
the neck: lobectomy
If hot nodule: treat
hyperthyroidism
Cold nodule w/o h/o
previous irradiation:
biopsy
Do lobectomy only if
malignant
Parathyroid
Located behind the thyroid glands
Most common tumor: parathyroid adenoma
Most common cause of isolated
hypercalcemia in adults
Most common cancer: adenocarcinoma
Men Syndromes
MEN Syndromes
MEN I: pituitary, pancreatic, and
parathyroid tumors ( Wermer Syndrome)
MEN II: medullary carcinoma of thyroid,
pheochromocytoma, plus or minus
parathyroid adenomas ( Sipple
Syndrome)
MEN III: MEN II plus neuroma or
ganglioneuroma but w/o PTH adenomas
Parafollicular Gland
Also found behind the thyroid glands
Most common tumor: adenoma
Most common cancer: medullary
carcinoma of thyroid (produces calcitonin)
Middle Mediastinum
Contains the heart
Heart has three layers: endocardium,
myocardium, and epicardium. Pericardium
encases the heart
321 309
8

Endocardium
Most common tumor: myxoma
Usually seen in left atrium
Diastolic plop
Middle aged female who passes out, only to
recover a few seconds later
Estrogen connection
Most common cancer: angiosarcoma (rare)
Myocardium
Related to skeletal muscle
Most common tumor: rhabdomyoma
Most common cancer: rhabdomyosarcoma
Epicardium
Hardly ever involved in neoplasia
Pericardium
Most common tumor: fibroma
Most common cancer: metastases
Lungs
Most common mass in children:
hamartoma
Most common mass in adults: granulomas
Most common tumor: adenoma
Most common cancer: metastases
Most common intrathoracic cancer:
squamous cell carcinoma
Most common primary cancer:
bronchogenic adenocarcinoma
Lung Cancers
CENTRAL: squamous cell carcinoma
( produces PTH)
Small cell carcinoma ( produces ACTH, ADH,
PTH and TSH)
322 310
9
Lung Cancers, cont
Peripheral: bronchogenic adenocarcinoma
and bronchoalveolar adenocarcinoma
Bronchoalveolar adenocarcinoma is the
only primary lung cancer NOT related to
smoking
Lung Cancers, cont
RISK FACTORS: primary smoker risk

increases with amount and duration

Radon
Second hand smoke
Sidestream smoke
Mainstream smoke
Pneumoconioses: all of them increase risk of
cancer except anthracosis
Pneumoconioses

Anthracosis
Asbestosis
Silicosis
Bissinosis
berryliosis

Treatment of Lung Cancer

Poor prognosis
Surgery done only if lesion smaller than
2cm in size and localized, and if there is a
V/Q mismatch
Chemo or radiation is effective against
small cell carcinomas
Pleural Cavity

Most common tumor: mesothelioma

Most common cancer: mesothelioma
Ferrugenous bodies
Psammoma bodies
Pleural thickening

Nasopharynx
Most common mass: polyp
Aspirin sensitive asthma: avoid aspirin or
NSAIDS
Most common tumor: fibroma
most common cancer: nasopharyngeal
carcinoma
Commonly seen in Chinese women
EBV association
323 311
10
Oral Cavity
Most common tumor: fibroma
Most common cancer: squamous cell
carinoma
Floor of mouth
Lower lip
Tip of tongue
Esophagus
Most common tumor: leiomyoma

 Most common cancer: squamous cell

carcinoma
Most common cancer in lower 1/3rd of
esophagus: adenocarcinoma
Risk factor: Barretts esophagus
Almost always ulcerates
Odynophagia
Poor prognosis ( < 5% 5 year survival)
Stomach
Most common tumor: leiomyoma
Most common cancer: adenocarcinoma
Virchows nodes
Leather water bottle appearance
Linnitis plastica
Signet ring cells
Kruckenberg tumor
Severe weight loss ( due to stomach
distention)
Risk Factors for UGI Cancers
Smoking
Alcohol
Nitrites
Japanese
Small Intestine
Most common tumor: leiomyoma
Most common cancer: adenocarcinoma
Most common cancer of the ileum:
lymphoma
Early UGI obstruction
Napkin ring lesion
70% of lymphoid tissue is located in the ileum
Appendix
Most common tumor: leiomyoma
Most common cancer: carcinoid
Does NOT metastasize
Carcinoid syndrome usually originates from
the (1) pancreas and (2) ileum
Puts out large amounts of serotonin (check urinary
5-HIAA
324 312
11
Colon

Most common
Most common
Napkin ring
Eaten apple
Pencil thin
Melena

tumor: leiomyoma
cancer: adenocarcinoma
lesion
core lesion
stool

 Third most common cancer, and most

common cause of cancer deaths in both
sexes
Colon cancer risk factors
Low fiber diet
High fat diet
Polyps
Ulcerative colitis
Polyps Liver
Most common mass: cyst
Most common tumor: adenoma and AVMs
Most common cancer: metastases
Most common primary cancer:
hepatocellular adenocarcinoma
Hepatic Adenoma
Associated with estrogen use or injected
steroids
Tends to rupture if abdominal pressure
rises significantly
Rupture can lead to acute life threatening
hemorrhage
AVMs
Connect arteries to veins
Increased venous oxygen
Decreased AVO2 difference
Risk:
Burst and bleed
Sequester platelets and cause bleeding
Sequester blood, leading to high output heart
failure
325 313
12
AVM Syndromes
Osler Weber Rondu: multiple AVMs in
the pulmonary circulation
Von Hipple Landau: multiple AVMs in the
abdomen and brain
Has an increased incidence of renal cell
carcinoma
Associated with chromosome 3p
Risk Factors for Hepatocellular
Carcinoma
Smoking
Alcohol
Hepatitis B
Hepatitis C
Shistosomiasis

 Analene dyes
Aflatoxin
Vinyl Chloride ( Angiosarcoma)
Benzene
Gallbladder
Most common tumor: leiomyoma
Most common cancer: adenocarcinoma
Poor prognosis because its hidden
beneath the liver
Thickened calcified gallbladder
Biliary Tract

Most common mass: choledochal cyst

Most common tumor: cholangioma
Most common cancer: cholangiosarcoma
Risk increase with chronic scarring
PRIMARY BILIARY CIRRHOSIS
Antimitochondrial antibodies
SCLEROSING CHOLANGITIS
Seen in ulcerative colitis

Pancreas
Most common mass: cyst
Most common tumor: adenoma
Most common cancer: Adenocarcinoma
Cholestatic jaundice: blocks biliary tract
High direct ( conjugated) bilirubin
Trousseau syndrome: migratory
thromphlebitis
Most common mucinous cancer
Pancreatic Adenomas
Glucagonoma: elevated glucose, lipids,
and ketones
Insulinoma (or nessidioblastosis): high
insulin and high C-peptide
Somatostatinoma: severe constipation
Vipoma: watery diarrhea
Gastrinoma (Z-E syndrome) elevated
gastrin levels all the time
326 314
13
Ovary
Most common mass: follicular cyst
Most common tumor: serous cystadenoma
Most common cancer: serous
cystadenocarcinoma
Highly malignant
Most mucinous cancer in women

Other Ovarian Tumors

Fibroma: associated with pleural effusion or
ascites ( Meigs syndrome)
Granulosa cell tumor: high estrogen
Yolk sack cancer: high AFP
Choriocarcinoma: high HCG
Sertoli-Leydig cell tumor: masculinization
Mucinous cystadenocarcinoma: very mucinous
(pseudomyxoma peritonei)
Teratoma: struma ovarii
Uterus
Most common mass: polyp
Most common tumor: leiyomyoma
Most common concer: adenocarcinoma
Uterine Polyp
Presents with passing of blood clots
Tx: surgery
Fibroids
Submucosal (90%): presents with
menorhagia
Subserosal: presents with pelvic pain or
pressure
Dependent on estrogen
Focal thickening; firm mass
Tx: OCPs; Leuprolide; surgery
Endometrial adenocarcinoma
Dependent on estrogen
Presents with metrorrhagia
Metrorrhagia after age 35 requires
endometrial biopsy
Tx: surgery
327 315
14
Cervix
Most common mass: warts
Most common tumor: fibromas
Most common cancer: squamous cell
carcinoma
Warts
Condyloma lata: secondary to syphilis
Fleshy appearance
Condyloma accuminatum: secondary to
HPV
Verrucous or mushroom like warts

 Tx: podophyllin drops; cryosurgery

Cervical cancer
Squamous cell carcinoma
Risk factors: HPV; other STDs
Tx: hysterectomy
Vagina
Most common mass: warts; Bartholin cyst
Most common tumor: fibroma
Most common cancer:
Upper half: squamous cell carcinoma from the
cervix
Lower half: skeletal muscle
Tumor: rhabdomyoma
Cancer: rhabdomyosarcoma (sarcoma botyroides)
Warts
Condyloma lata: secondary to syphilis
Fleshy appearance
Condyloma accuminatum: secondary to
HPV
Verrucous or mushroom like warts
Tx: podophyllin drops; cryosurgery
Bartholin cyst
Congenital
Fluctuant mass behind the labia majora
Complication: infections/ abscess
formation
After first infection: treat with antibiotics
After second infection: surgery
(marsupialization)
328 316
15
Rhabdomyoma/
Rhabdomyosarcoma
90% of rhabdomyosarcomas occur under
age 3 years
Increased incidence in Tuberous Sclerosis
Sarcoma botyroides: looks like a ball of
grapes when removed
Kidney

Most common mass: cyst

Most common tumor: adenoma
Most common cancer:
In children: Wilms tumor
In adults: renal cell adenocarcinoma

Wilms tumor

 Renal cancer in children

Classic clues: aniridia and
hemihypertrophy
Renal Cancer
90% occur on superior pole of kidney
Presentation: painless hematuria; flank mass
Most vascular cancer
Produces erythropoietin
Metastasizes via retroperitoneum
Favorite metastatic site: lungs (cannon ball
metastases
20% contralateral recurrence
Renal Cancer, cont
Risk factors: smoking; Von Hippel Landau;
Tuberous Sclerosis
Evaluation: UA; sonogram;IVP; CT scan;
angiogram;
Tx: surgery
Annual CT scans after surgery to detect
contralateral recurrence
Adrenal Gland
Most common mass: cyst
Most common tumor: adenoma
Most common cancer: adenocarcinoma
329 317
16
Adrenal adenomas

Glucagonoma
Insulinoma
Somatostatinoma
Pheochromocytoma

Bladder
Most common mass: diverticulum
Most common tumor: leiomyoma
Most common cancer (including ureters):
transitional cell adenocarcinoma
Bladder diverticulum
Complications: UTIs and kidney stones
Tx: surgery
Bladder Cancer
Transitional cell adenocarcinoma
Multiple primaries
Presents with painless hematuria

 Tx: surgery; radiation

Risk factors: smoking; anilene dyes; benzene;
aflatoxin; cyclophosphamide
Squamous cell carcinoma
Schistosoma hematobium
Prostate
Most common tumor: BPH
Most common cancer: adenocarcinoma
BPH
Presentation: strains to urinate; weak
stream; dribbling after urination; frequency
and urgency
Tx: terazicin/doxazocin; tamsulocin;
fenesteride; TURP
330 318
17
Prostate Cancer
Most common cancer in men
Second to lung cancer for cancer deaths
in men
Tx: surgery; hormonal therapy or radiation
after surgery
Prostate cancer screening
Age 35: baseline rectal/prostate exam
After age 40: annual rectal/prostate exams
Annual sigmoidoscopy begins after age 40
After 2 normal annual sigmoidoscopies,
repeat in 3 to 5 years
Colonoscopy every 3 to 5 years begin at
age 50
Full colonoscopy should follow any abnormal
sigmoidoscopy
Testicles

Most common mass:

In newborns: hydrocele
In children and adults: hematoma
In older adults: varicicele
Most common tumor: adenoma
Most common cancer:
In first year of life: yolk sak cancer
In teens to adults: seminoma

Testicular exams
Begin in adolescence
ANY firm testicular mass: perform an
orchiectomy

Skin
Most common mass:
Skin tag (acrochordon)
hemangioma
Most common tumor: fibroma
Most common cancer: basal cell
carcinoma
Most common malignancy: squamous cell
carcinoma
Skin Tags
Very common
Tx: shave it off
331 319
18
Hemangiomas
Found anywhere on the body
An enlarged flat blood vessel
Tx: observation for 18 months; inject with
steroids; laser surgery
fibromas
Very common
Easy to remove if you need to do so
Many of them seen in neurofibromatosis
Neurocutaneous Diseases
Neurofibromatosis
Sturge Weber
Tuberous Sclerosis
All Neurocutaneous Diseases
have
Mental retardation
Cerebral calcifications
Seizures
Neurofibromatosis
Caf au lait spots (at least 3 with 1.5 cm
diameter minimum); hyperpigmented
macules
Neuromas
Fibromas
Chromosome 17/22 involved
Type 1: chromosome 17; peripheral
neuromas
Type 2: chromosome 22; central neuromas
Sturge - Weber syndrome

 Port wine stain on face ( V-1)

Angiomas of retina and brain associated
332 320
19
Tuberous Sclerosis
Ashen leaf spots (hypopigmented
macules)
Tubors: primary brain tumors
Rhabdomyomas and rhabdomyosarcomas
of the heart
Renal cell carcinoma
Basal cell carcinoma
Most common skin cancer; but, it does
NOT behave malignantly
Usually found on the face from sun
exposure
Wide resection is curative
Squamous cell carcinoma
Behaves malignantly
Ulcerates
Main risk factor: sun exposure (use SPF
15 )
Predisposing skin diseases: actinic
keratosis; Bowens disease
Diseases with increased risk: albinism;
vitiligo; porphyria cutanea tarda; PKU;
Wiscott-Aldridge; Jobs syndrome
melanoma
The MOST malignant skin cancer
Melanotic nevi are risk factors
Malignant risk:
A rea
B orders
C olor
D epth of invasion (worst prognostic factor)
Bone neoplasia Epiphysis
Made of cartilage
Most common tumor: chondroma
Most common cancer:chondrosarcoma
333 321
20
Diaphysis
Made of osteocytes
Most common tumor: osteoma

 Most common cancer: metastases

Most common primary cancer:
osteosarcoma
Metaphyseal osteosarcoma
Seen mainly in adults
Codmans triangle
Star burst effect on the cortex
Diaphysis

Made of osteocytes
Most common tumor: osteoma
Most common cancer: metastases
Most common primary cancer:
In children: Ewings osteosarcoma
In adults: plasmacytoma or multiple myeloma

Ewings osteosarcoma
Primary bone cancer in children
Onion skinning seen in bone
T(11/22)
Multiple myeloma
Plasmacytoma: when single lesion
Multiple myeloma: MULTIPLE osteolytic
lesions
IG-g: most common heavy chain
Kappa: most common light chain
Hypercalcemia
Ruleaux formation
Breasts
Most common mass: cyst
Most common tumor:
< 25y/o: fibroadenoma
>25y/o: fibrocystic disease
Most common cancer: intraductal
adenocarcinoma
334 322
21
Fibroadenomas
Estrogen dependent
Enlarges in first two weeks of menstrual
cycle
Fibrocystic disease
Progesterone dependent
Enlarges in the two weeks preceeding
menses
Has greenish fluid on aspiration

Intraductal adenocarcinoma
Estrogen dependent
Top locations: upper outer quadrant;
nipple
Usually presents with a dimple
Metastases can be osteolytic or
osteoblastic
Other breast neoplasms
Intraductal papilloma: nipple bleeding
Lobular adenocarcinoma: contralateral primary;
cells lined up in single file
Comedocarcinoma: focal areas of necrosis
Inflammatory adenocarcinoma: peau dorange
(infiltrates lymphatics); the most malignant
cancer
Cystsarcoma phylloides: a sarcoma; explodes out
of the breast, then stops growing; wide resection
is adequate
Breast cancer screening
Baseline exam: age 35
Age 40 to 50: annual breast exam by
doctor; monthly SBE
Age 50 to 79: add annual mammogram
Family h/o breast cancer: begin
mammography 5 years before the age of
the index case
Cystic breast mass
History
Physical
Ultrasound
Fine needle aspiration: diagnostic and
therapeutic
335 323
22
Firm breast mass
History
Physical
Mammogram
Lumpectomy
Send to pathologist for definitive
identificaton
Benign firm breast mass
After lumpectomy, we are done
Malignant firm breast mass

 After lumpectomy, perform a modified

radical mastectomy
Nodal dissection
Check for estrogen and progesterone
receptor positivity
Tamoxifin or Roloxifene for estrogen
positive cases
Chemotherapy for premenopausal women
and radiation for postmenopausal cases
Tamoxifin / Roloxifene
Anti-estrogen at the breast and pituitary
Proestrogen at the bone, liver, and the
uterus (Tamoxifin only)
Cancer Profile
Signs and symptoms: low energy state
Cancer more common in males: under age
30 and after age 50
Cancer more common in women: age 30
to 50
Most common cause of death: infections,
except for uterine and cervical cancers
(renal failure)
Cancer Antigens
Prior to surgery: associated with
After surgery: if it rises again, there is a
95% chance you have recurrence or
metastases
336 324
23
Cancer Antigens
PSA
CEA
S-100
AFP
HCG
C-MYC
L-MYC
N-MYC
Desmin
Vimentin
Ca-125
Ca-19
BCL-2
RET
RB
Cancer Markers
T(9/22)

 T(8/14)
T(14/18)
T(11/22)
T(15/17)
ERB
HER 2 NEU
BRCA
P53
THE END
337 325
338 326
Microbiology & Immunology:
Week Four
339 327
340 328
1
Immunology
LISCENCED TO KILL
Immunology
Study of the immune system
Antigen
HAPTEN
Less than 6000D
Too small to set off the
immune system by
itself
IMMUNOGEN
Greater than 6000D
Large enough to set
off the immune system
by itself
The most important factor that
determines Immunogenicity is
Antigen
HAPTEN
Less than 6000D
Too small to set off the
immune system by
itself
IMMUNOGEN
Greater than 6000D
Large enough to set
off the immune system
by itself

341 329
2
Carrier Effect
What macrophages do for a living

Ingest
Phagosome formation
Digest
Present
MHC II complex
V-beta region
Invariant chain is displaced
IL-1 is released

Making use of the carrier effect

IL-1
Fever
Nonspecific symptoms of illness
Recruits T-helper cells
Fever
Def: one degree above normal body temp
Raises heart rate 10bpm for each degree
rise above normal
Allows immune cells to come around
faster
Causes secretion of Ig-A
Infections that cause heart block
Legionella
Lyme disease
Chagas disease
Diptheria
Typhoid fever
342 330
3
Fever

Means that IL-1 showed up

By itself can NOT tell you the cause
The pattern of fever can be diagnostic
Causes discomfort at about 101 degrees F

Antigen
HAPTEN
Less than 6000D
Too small to set off the
immune system by
itself

IMMUNOGEN
Greater than 6000D
Large enough to set
off the immune system
by itself
How do you make an Immunogen
less immunogenic?
Detergent
Disrupts the ADHESION of pathogens by
disrupting membrane forces
Antiseptic/Disinfectant
Phenol is most common
Iodine is most common in the hospital
These chemicals DESTROY the
membrane and INACTIVATE endotoxin
These chemicals actually KILL 99% of
germs
Sterilization
For spores
A dormant form of a bacteria
CAN NOT replicate in this form
CAN still release toxin, especially when
exposed to heat
Bacillus and Clostridium
Done at 121* C with VAPORIZED heat
343 331
4
Most immunogenic bacteria
SHIGELLA
Only 8 to 10 microbes required to get a full
infection
The two arms of the Immune
system
HUMORAL
BLOOD
CELL MEDIATED
TISSUE
The two arms of the Immune
system
HUMORAL
BLOOD
B-CELLS
NEUTROPHILS
CELL MEDIATED
TISSUE
T-CELLS
MACROPHAGES

MACROPHAGES
Microglia: brain
Type-1 pneumocytes: lungs
Kuffler cells: liver
RES cells: spleen
Dendritic cells: lymph nodes
Osteoclasts: bone
Mesangial cells: kidneys
M cells: Peyers patches
Langerhans cells: skin
Monocytes: blood
Connective tissue: epitheloid cells; giant cells; histiocytes
The two arms of the Immune
system
HUMORAL
BLOOD
B-CELLS
NEUTROPHILS
BACTERIA
CELL MEDIATED
TISSUE
T-CELLS
MACROPHAGES
ALL ELSE!!!
All Else
Virus
Fungus
Mycobacteria
Protozoa
Parasite
Neoplasm
344 332
5
Inflammation Acute Inflammation
Look for SWELLING or NEUTROPHILS
Chronic Inflammation
Cellular infiltrate: T-cells and macrophages
What you see on biopsy: fibrosis
What you see on x-ray: calcifications
Can it really be this easy?
Can it really be this easy?
YES!
THE END
345 333

6
Or Maybe Not. Let The Leukocytes Loose!
346 334
1
Immunodeficiencies
LACKING A LITTLE
Humoral Immune Sytem
Protect the blood
Humoral Immune Sytem
Protect the blood
B cells
Humoral Immune Sytem
Protect the blood
B cells
Neutrophils
Humoral Immune Sytem

Protect the blood

B cells
Neutrophils
Bacterial infections

Cell mediated Immune System

Protect the tissues
347 335
2
Cell mediated Immune System
Protect the tissues
T-cells
Cell mediated Immune System
Protect the tissues
T-cells
Macrophages
Cell mediated Immune System

Protect the tissues

T-cells
Macrophages
Nonbacterial infections

Cell mediated Immune System

Protect the tissues
T-cells
Macrophages
Nonbacterial infections
Virus
Fungus
Mycobacterium
Protozoa
Parasite
neoplasm
T-cell immunedeficiencies
DiGeorge syndrome
Chronic mucocutaneous candidiasis
Steroids
Cyclosporine
Hairy cell leukemia
SCID
Wiscott-Aldridge syndrome
HIV
DiGeorge syndrome
Third pharyngeal pouch is missing
Inferior parathyroids glands are missing
The only immunodeficiency with
hypocalcemia
348 336
3
Chronic Mucocutaneous
Candidiasis
A T-cell defect at a submolecular level
T-cells can fight everything else under all
else except candida
Candida infections on skin and mucous
membranes
Causes chronic fatigue syndrome
Steroids
Anti-inflammatory actions
Kills T-cells and eosinophils
Inhibits macrophage migration
Stabilizes mast cell membranes
Stabilizes endothelium
Inhibits phospholipase A
Physiologic actions (catabolic)
Proteolysis
Gluconeogenesis
Upregulates all receptors during stress ( permissive)
Steroids
Prednisone
Hydrocortisone

Methylprednisalone
Triamcinalone
Beclamethasone
Betamethasone
Fluticasone
Mometasone

Fludrocortisone
Danazole
Cypropterone
Megesterol
Dexamethasone

Cyclosporine
Revolutionized transplantations in America
Prolongs the longevity of transplanted
organs
Inhibits calcineurin which is needed to
produce the interleukins
Causes gingival hyperplasia and
hirsutism
Tacrilimus
Now used in place of cyclosporin due to
much fewer side effects
Hairy Cell Leukemia

Most commonly a B-cell leukemia (75%)

More frequently a T-cell leukemia (25%)
Has hairy cell membrane projections
Tartrate Resistant Acid Phosphatase (TRAP)

349 337
4
T-cell Lymphomas
Mycosis Fungoides ( cutaneous)
Sezary syndrome ( present in the blood)
T-cells have characteristic indented cell
membrane
SCID
Involves adenosine deaminase deficiency
DNA synthesis is disrupted
Affects all rapidly dividing cells
Affects T and B-cells
Bone marrow transplant is now the
standard of care
Wiscott-Aldridge syndrome
Involves T-cell interaction with B-cells
X-linked recessive

Fair-skinned
Eczema
Thrombocytopenia
Normal Ig-A and Ig-E levels
Increased incidence of lymphoma

B-cell Immunodeficiencies
Brutons agammaglobulinemia
CVID
Leukemias
Lymphomas
Plasmacytoma
Multiple myeloma
Heavy Chain disease
Selective Ig-A def
Selective Ig-G2 def
Jobs syndrome
SCID
Wiscott-Aldridge syndrome
Brutons Agammaglobulinemia

X-linked recessive
Cell signalling is defective
B-cell count is normal; function is lacking
Early onset

CVID
Late onset Brutons ( after first year of life)
B-cell count is also normal; B-cell function
is lacking
Cell signalling is defective
350 338
5
Leukemias
98 B-cells for every T-cell in periphery
Lymphomas
98 B-cells for every T-cell in periphery
Plasma Cell Cancer
Plasmacytoma: only ONE lesion
Multiple Myeloma: MULTIPLE osteolytic
lesions
Ruleaux formation
Hypercalcemia
Ig-G is most common M-spike
Kappa light chains are most common Bence
Jones protienuria
Heavy Chain Disease

 Ig-A Multiple Myeloma of the bowel wall

Ig-A plasma cells visible on biopsy
Causes malabsorption
Selective Ig-A def
Many mucosal infections
Runs with selective Ig-G2 def 95% of time
Anaphylaxis during a transfusion
Must use a filter for all subsequent
transfusions or use blood from another Ig-A
def patient
Selective Ig-G2 def
Runs with selective Ig-A def
Ig-G is main opsin ( coats encapsulated
organisms)
Recurrent encapsulated organism
infections
351 339
6
Encapsulated Organisms
Gram positive
Streptococcus
pneumonia

Gram negatives
Salmonella
Klebsiella
H. Influenza B
Pseudomonas
Nisseria
citrobacter

Jobs syndrome

Cell signalling defect

Increased Ig-E
Fair-skinned
Red-haired female

The Final Two

SCID
WISCOTT-ALDRIDGE
Neutrophil Defects
Myeloperoxidase def
NADPH-oxidase def (CGD)
Absolute neutropenia
Myeloperoxidase def
Recurrent gram positive infections

Chronic Granulomatous Disease

(CGD) NADPH-oxidase def
X-linked recessive
Negative NBT test ( detects nadph-oxidase)
352 340
7
Absolute Neutropenia
ANC = ( % Neutrophils + % bands) WBC
< 2500
<1500
<1000
At risk for staph aureus and pseudomonas
infections
If any fever: cover staph aureus with one
antibiotic and pseudomonas with two
antibiotics
At Risk for Staph and Pseudomonas
Infections
Absolute neutropenia
Cystic Fibrosis
Burn patients
Diabetics
Macrophage Defects
NADPH-Oxidase def ( CGD)
Chediak-Higashi
Chediak-Higashi syndrome
Lysosomes are slow in fusing with
ingested pathogen
Lysosomal inclusions
Albinism
HIV
The two populations with the highest
incidence are heterosexual Black women
and the elderly
Lowest risk population: prepubertal female
HIV likes acidic medium, mucosae, and
CD-4 receptors
Where CD-4 receptors are found
Female cervix
Blood vessels
Macrophages
T-helper cells
CNS
Testes
HIV is only virus that does NOT penetrate
the cells; it injects its RNA into the cells

353 341
8
Cancers Common in HIV
Cervical cancer
Kaposi sarcoma ( helped by Herpes 8)
CNS and testicular lymphomas
HIV Infection
Attaches to CD-4 receptor using GP120
GP 41 has no known function
Injects the RNA inside
POLymerase protein is used to integrate
the RNA into host genome
Reverse transcriptase is used for
transcription
P17 and P24 used for assembly
To Prevent Attachment of HIV
CCR5
CCR4
Screening for HIV

ELIZA ( Ig-G antibody test)

Western blot ( detects protein)
Northern blot ( detects RNA)
Southern blot ( detects DNA)
PCR ( amplifies RNA or DNA)

Screening for HIV, cont PCR

MORE sensitive than Southern blot or
Northern blot
Used for screening only in the first 18
months of life ( moms Ig-G interferes with
ELIZA)
354 342
9
T-helper cell Counts
Normal: 800 to 1200
normal in newborns: 1500
Begin treatment: CD4 counts < 500
Pediatrics: < 50% ( 750)
Begin PCP prophylaxis
CD4 count < 200
Pediatrics: < 20%
Begin MAI prophylaxis
CD4 count < 100
Pediatrics: <10%
HIV Treatment

START with two nucleoside inhibitors and

one protease inhibitor
AZT
3TC
4DT
DDI or DDC
Rotenovir; Indinavir; Sequinavir
PCP Prophylaxis