Fever

Kaplan:
Prosopagnosia: inability to recognize faces. Usually caused by
bilateral lesion of visual association cortex.
Anosagnosia: deficit in recognition about one's illness, due to
lesions of the non-dominant parietal lobe.
UW:
The benefit from smoking cessation is the single most important
modifier of mortality.
Mortality modifiers include:
Aspirin therapy and tight blood glucose control.

Diet, exercise and other therapies for tight glycemic control do

help prevent microvascular complications but the role of tight blood
glucose control in the prevention of macro vascular disease is still
unproven.

UW: catecholamines synthesis and catabolism:

Diet

Phenylalanine
BH4
Phenylalanine hydroxylase
Defected in PKU

Tyrosine

See page 7 for

tyrosine
metabolism

Tyrosine hydroxylase
Tetrahydrobiopterin
( BH4)
Alpha methyl
Dopa ( dihydroxyphenaylalanine )
tyrosine inhibits
PLP
This cofactor is also required by:
Phenylalanine hydroxylase
NO synthase
Tryptophan hydroxylase, which is used
to make serotonin and melatonin. Those
three in addition to tyrosine
hydroxylase. Defect in dihydrobipterin
reductase ( responsible for making
tetrahydrobipterin ) also results in

PKU

This enzyme is
induced by cortisol.

Dopa carboxylase

Dopamine
Vit C

this enzyme.
Used only in
pheo.

Dopamine beta hydroxylase

Nore-epi.
Phenylethanolamine-Nmethyltransferase ( PNMT ).
SAM is required here because
this is a methylation step.

Epi ( adrenal medulla )

COMT and MAO are the enzymes responsible for brake down of
catecholamine.

Epi
Nore epi

COMT

MAO

Dihydromandalic acid

Noremetanephrine

COMT
Metanephrine
MAO

Vanillylmandelic
acid ( VMA )

Tyrosine metabolism: UW

Dihydrobiopterin reductase

BH4

Phenylalanine

PKU:
Autosomal recessive
Mental and growth retardation
Seizures, fair skin, eczema
Mousy oder
Tyrosine become essential
Usually due to phenylalanine hydroxylase deficiency.
Small % due to BH2 reductase deficiency ( this is
known as malignant or atypical PUK ).

Melanin
( in melanocytes )

BH2

Phenylalanine
hydroxylase

Tyrosine

DOPA

Homogentistic acid
( alkapton )

Homogentisate oxidase

Catecholamine

Maleylalacetoacetate
Alkaptonuria:
Autosomal recessive
Dark connective tissues ( homogenstic
acid binds to collagen ).
Fumarylacetoacetate
Pigmented sclera
Urine turn black on standing due to
oxidation of homogentistic acid.
Debilitating arthralgias
Fumarate

TCA cycle

Excess accumulation of
phenylalanine or its products
leads to brain damage in PUK.
Phenylalanine

Phenylacetate

Phenylpyruvate

Phenyllacetate

Tryptophan

BH4

5-hydroxytryptamine

Serotonin

B6
Niacin

NAD/NADH

Melatonin

UW: steroid receptors

Found in the cytoplasm and are known as zinc finger proteins
that, while inactive, is bound to heat shock proteins ( especially
HSP 90 and HSP 56 ). Once steroid hormone makes a contact with
its receptors, the HSP are released into cytoplasm. This exposes
the DNA binding area in the receptor, and the receptor-hormone
complex is transported to the nucleus where they activate
transcription of certain genes.

Steroid receptor
bound to HSP

HSP is released after the

attachment of steroid
hormone

Nucleus

Hormone-receptor complex
Steroid

Methemoglobinemia, UW:

Drugs e.g. Nitrate

Fe++
Hemoglobin

Fe+++
Methemoglobin

Binds tightly to cyanide

Causes dusky discoloration of skin
Can't carry oxygen

Tyrosine kinase VS Serine kinase, UW:

TNF-alpha, catecholamine, glucocorticoids, glucagon and intracellular
free fatty acids increase insulin resistance by activating serine
kinase ( instead of tyrosine kinase ) that results in increase
phosphorylation of serine residues and antagonize insulin.
Phosphorylation of threonine also thought to result in same effect.

Lysosomal storage diseases:

Sphingolipids synthesis
Sphingosine
Fatty acid

Neimann-Pick

Choline

Ceramide
Glucose

Sphingomyelin

Krabbe's

Gaucher
Glucocerebroside

Glactocerebroside

Metachromatic
leukodystrophy

Fabry's
Ceramide trihexose

Galactose

Gangliosides (GM3)
Tay-Sachs

Sulfatides
e.g. Cerebroside
sulfate

Gangliosides (GM2)
Sphingolipids break down occurs in the lysosomes and just takes the reverse
pathway. When one of the breakdown enzymes is deficient, lysosomal storage disease
results ( 6 are sphingolipidosis, and 2 are mucopolysacharidosis, Hurler and Hunter ).
The above diagram shows only sphingolipidosis.
> Pick and GaUcher have Big ( hUge liver ). Pick has red macula, Gaucher is not.
> Pick and Tay-Sac have red maculae. Pick has Big liver, Sac is not.
> Hurler is blind, Hunter is not.

The deficient enzymes

Sphingosine
Neimann-Pick

Ceramide

Krabbe's
Sphingomyelinase
Gaucher
Beta Glucocerbrosidase Beta galactocerbrosidase
Sphingomyelin

Glucocerebroside

Metachromatic
leukodystrophy
Arylsulfatase A

Fabry's
Alpha galactosidase A
Ceramide trihexose

Galactocerebroside

Gangliosides (GM3)
Hexosaminidase
Tay-Sachs
Gangliosides (GM2)

Nemonic:
Upper raw : NGK ( No Guy Killed )
Lower raw : FTM ( For That Money )

Sulfatides
e.g. Cerebroside
sulfate

Angiokeratoma of Fabry's

Hepatosplenomegally,
Cherry-red macula and
foam cell of Niemann-Pick

Tay-Sacks

No hepatosplenomegally ( VS Niemann )

Cherry red macula

Whirled
Brain problems

Sandhoffs disease, Ganglioside GM2, globoside

Same as Tay-Sachs disease, but more rapid course

Niemann-Pick

Zebra bodies

Severe mental retardation

Big organs

Hepatosplenomegally
Huge organs

Gausher's
No red macula ( VS Niemann )

Crunched up paper
Aseptic bone necrosis

All of them cause severe neurological deterioration except Gaucher, which spares the
brain and affects the liver.

Fabry's

Metachromatic
leukodytrophy

Angiokertomas

Ataxia

There is also what is known as Adrenoleukodystrophy, which results form failure of

peroxisomal Beta oxidation of very long chain FAs.

Hurler's
Gargoylism
Hunter's

Corneal clouding

Receptors and Tyrosine kinase, Kaplan Qbank:

Some tyrosine kinase receptors ( TKRs ) have intrinsic tyrosine

kinase activity, e.g. HER-2. These receptors are primary receptors
for growth factors such as epidermal GF, transforming GF and
insulin.
Note, growth hormone receptors are outliers in that, they lack
this intrinsic tyrosine kinase activity. Upon binding with the
hormone, the receptor binds to the free-floating tyrosine kinase
and then the signal initiated. These kinds of receptors are known
as JAK-STAT. Cytokines work via these receptors.
Many TKRs are examples of protoncogenes, since activating
mutation leads to continuos activity even in the absence of the
growth factors. See the following table
Receptor
Abbreviation Chemotherapy
Epidermal growth factor receptor
Cetuxima
HER1

Associated
Variable

Epidermal growth factor receptor 2 HER2

Trastuzumab

Breast cancer

Receptor for neurotropic factor

RET

Experimental

NEN 2a and 2b

Platelet derived GF receptor

PDGF-R

Imatinib

c-KIT

Imatinib

Receptor for stem cell factor

No-receptor tyrosine kinase

ABL

Imatinib

Variable

Gastrointestinal stromal tum

CML

UW: cold vs worm agglitonins

Cold agglutinins cause agglutination of RBCs when a sample of blood
contains these antibodies is chilled. They occurs in infections such as
mycoplasma and EBV. And some malignancies. They are IgM in nature
and directed against ABO antigens.

Internet:
Warm antibodies are IgG in nature and are formed against Rh antigen (D antigen) and
these can cross the placenta. this antibody is responsible for Hydrops fetalis in Rh
incompatibility. Also IgG antibodies produced in Auto Immune Hemolytic anemia where IgG
antibody coated erythrocytes are destroyed in the spleen.
Cold antibodies are IgM in nature and are produced against ABO blood group, responsible
for hemolysis in ABO mismatch transfusion. Also IgM antibodies are produced in certain
infections like Mycoplasma pneumoniae called Cold Agglutinins which can causes
hemolysis. In case of cold antibodies -the IgM binds to RBC and Activates complement and
it is complement mediated hemolysis and this occurs intravascularly.

Cord factor
Cord factor refers to trehalose dimycolate, a virulence factor
and glycolipid cell-wall component of virulent strains of
Mycobacterium tuberculosis and closely related species. It is a
surface glycolipid which blocks macrophage activation by IFN-,
induces secretion of TNF and causes Mycobacterium
tuberculosis to form cords in vitro. This is the main virulence
factor for the mycobacterium tuberculosis that makes it
resistance to anti-tuberculosis medications.
Mycobacterium that does not have this cord factor is not able
to cause disease.

H. Influnzae

S. pneumoniae after otitis media

Staph. Aureus
Meningococci, the answer

T.B meningitis

Bacterial vaccines, UW:

Live attenuated : BCG and typhoid vaccine.
Note: live attenuated vaccines are commonly used for viral
diseases.
Killed vaccines: those of anthrax, cholera, pertussis and plaque
Yersinia pestis.

Inactivated toxin vaccines : diphtheria, tetanus

Cryptococcus : pigeons
Histoplasma: bats, birds, caves

Path. UW:
Neuroblastoma is the most common extracranial childhood cancer.
Develops from neuroblast located in the adrenal medulla.
2 yrs old
Solid sheets of small cells with dark nuclei and scant cytoplasm
Renal mass, HTN, anorexia
Associated with N-myc amplification

FA:
The most common tumor of the adrenal medulla in children. Can
occur anywhere along the sympathetic chain. Homovanillic acid
(HVA), a breakdown product of dopamine, elevated in
urine. Less likely to develop hypertension. Overexpression of Nmyc oncogene associated with
rapid tumor progression.

MAP-kinase pathway, UW:

Growth factor
Membrane

P
SH proteins,
SOS proteins

SH proteins,
SOS proteins

Inactive

Mutation in Ras can lead to

inability to split GTP resulting in
permanently active Ras that
leads to continuos stimulation of
cell growth and cancer.

MAPkinase

Gene transcription

Active
Ras-GDP

Ras-GTP

Inactive

Active

Pi

GTPase activating protein

MAPkinase kinase

RAF

Ras over expression occurs in

pancreatic, gall bladder, colon,
endometrial, thyroid and lung
cancer.
See next page

Growth factors signal transduction systems

RAS-MAP kinase
PI3K/Akt/mTORA
Inositol phospholipid
cAMP
JAK/STAT

Prolactinomas, UW:

Cystic fibrosis, UW

In milder forms of CF where increase in sweat chloride is not seen we can perform this
transepithelial difference. there is less chloride secretion but relatively increased Na and water
absorption, hence increased negativity on the membrane ie incresed potential difference.

Normally glands other than sweat glands

Cl
CFTR

Normally in sweat glands

Cl
Secretion

When CFTR is mutated, secretion

content of Cl will be low.

Sweat

When CFTR is mutated, sweat

content of Cl will be high.

UW, cardio:
The best auscultatory indictor for mitral stenosis severity is
the length of interval between A2 and the opening snap. They
are inversely related, i.e. The more severe the stenosis is, the
shorter the interval between A2 and OS. In modren practice
however, the severity of MS is determined by measuring the
transvalavular pressure gradient using 2D doppler.
While the best auscultatory indictor for mitral regur. severity
is S3 gallop of the left ventricle.

Kaplan: five tumors associated with overproduction of

erythropoeitin:
HCC
Renal cell carcinoma
Hemangioblastoma
Pheochromocytoma
Uterine myomata

Adenoma to carcinoma sequence, UW:

Normal epithelium
APC

Adenomatous Polyposis Coli

Early adenoma
Small adenoma

K-Ras
Late adenoma
Large

P53, DCC

Over expression of COX

Adenocarcinoma
APC : is a tumor suppressor gene. It controls cellular division, intercellular
attachment, and cellular movement ( with the tissue and out of the tissue ).
K-Ras: a protooncogene. Mutated K-Ras encodes for a protein that has no
ability to inhabits cell cycle but stimulate it ( growth signaling system ).
Note: aspirin aspirin impedes progression from adenoma to carcinoma.

Adenoma less than 1 cm is unlikely to undergo malignant

transformation, while those who are more than 4 cm has a 40% risk of
malignancy.

Colonic polyps

As veiwed under microscope

Adenomatous (70%)
Can develop into cancer
Divided into tubular and villous

Nonadenomatous (30%)
Very low risk
Hyperplastic and other
less common types

Colonic polyps display a variety of histologic patterns. Most of them are

non-neoplastic and do not increase the risk of colon adenocarcinoma. Nonneoplastic polyps include:
1. Hyperplastic polyps are composed of well-differentiated mucosal cells
that form glands and crypts.
2. Hamartomatous polyps consist of mucosal glands, smooth muscle and
connective tissue. They may occur sporadically or in Peutz-Jeghers
syndrome or juvenile polyposis.
3. Inflammatory polyps are seen in ulcerative colitis and Crohn disease. They
are composed of regenerating intestinal mucosa.
4. Lymphoid polyps are found in children. They consist of intestinal mucosa
infiltrated with lymphocytes.
Unlike non-neoplastic polyps, adenomatous polyps contain dysplastic mucosal
cells and can transform into adenocarcinoma. The following criteria determine
the malignant potential of adenomatous polyps:
1. Degree of dysplasia.
2. Histologic pattern: villous adenomas are more likely to undergo malignant
transformation than tubular adenomas.
3. Size: adenomas >4 cm have 40% risk of becoming malignant; those <1 cm
are most likely benign.

Translocations:
8:14

The resultant
Increased c-MYC

11:14

Increased Cyclin D

14:18

Increased BCL2

9:22
Ph+

ABL, Tyrosine kinase

activity

The tumors
Burkitts

Mantle cell lymphoma

Follicular lymphoma

CML

Note: chromosome 14 contains Ig heavy chain gene.

Desmosomes/ HemiDesmosomes:

HemiDesmosomes, the
linking protein is
integrin.

Desmosomes, the anchoring

proteins are known as
cadherins ( desmogleins and
desmocollins ).

Basal lamina

BCL2
Apoptosis

BAX
Failure of repair

Cyclin D with Cdk4,

Cyclin E with Cdk2

cell, inhibiting their kinase activity and preventing phosphorylation of proteins.

6. Without proper protein phosphorylation, the cell cycle cannot continue until DNA
mismatches have been repaired.
7. Inhibitory processes are reversed once the DNA mismatches are repaired, as p53
levels drop in response to lowered levels of DNA mismatches.
8. As p53 levels drop, the binding capacity of p21 also drops.
9. As p21 levels drop, these proteins diffuse off the cyclin-CDK proteins, which then
can resume their normal activity.

In the event that there is excessive DNA damage, the BAX gene is
activated. BAX gene inhibits the BCL2- antiapoptosis gene causing release
of cytochrome C from the mitochondria and apoptosis of the cell.

Phakomatoses are inconsistently defined, and there is not a

consensus about what conditions are included in this category.
Conditions included are:
" SANTA "
Neurofibromatosis
Sturge weber
Tuberous sclerosis
Angiomatosis retinae
Ataxia telangiectasia
Neurofibromatosis
Sturge-Weber syndrome
Tuberous sclerosis
von Hippel-Lindau disease
Ataxia telangiectasia
Incontinentia pigmenti
Nevoid basal cell carcinoma syndrome
Wyburn-Mason Syndrome
Important are:
VHL
Osler-Weber-Rendu ( Heridetary hemorrhagic Telangectasia )
Sturge-Weber ( encephalotrigeminal angiomatosis )
NF-1,2
Tuberous sclerosis
Ataxia Telangectasia

# VHL: Findings: hemangioblastomas of retina/cerebellum/medulla; the

majority of affected individuals develop multiple bilateral renal cell
carcinomas and other tumors. Associated with deletion of VHL gene (tumor
suppressor) on chromosome 3 (3p ). Results in constitutive expression of HIF
(transcription factor) and activation of angiogenic growth factors. Von HippelLindau = 3 words for chromosome 3
# Osler-Weber-Rendu ( Heridetary hemorrhagic Telangectasia ): blood
vessels disorder, AD , recurrent epistaxis, telangiectasias.
# Sturge-Weber ( encephalotrigeminal angiomatosis ): sporadic occurrence,
angiomas, port wine stain over v1 distribution
# NF-1,2
# Tuberous sclerosis: Findings : facial lesions (adenoma sebaceum),
hypopigmented "ash leaf spots" on skin, cortical and retinal hamartomas,
seizures, mental retardation, renal cysts and renal angiomyolipomas, cardiac
rhabdomyomas, increased incidence of astrocytomas. Incomplete penetrance,
variable presentation.
# Ataxia Telangectasia: is an autosomal recessive primary immunodeficiency
disorders associated with abnormal thymic development, progressive
cerebellar ataxia, and oculocutaneous telangiectasia. The responsible gene,
located on chromosome 11, leads to a generalized defect in the ability to
repair damage to DNA. Such a defect accounts for the frequent occurrence
of malignancies, particularly lymphomas, and the exquisite sensitivity to
therapeutic irradiation. There is evidence for both humoral and cellular
immunodeficiency;most patients have depressed IgA and IgE levels as well as
cutaneous anergy. Sinopulmonary infections are common with severe resultant
respiratory insufficiency, often associated with bronchiectasis.

Types of intracranial hemorrhage, UW:

Rapidly Progressively Glomerulonephritis ( RPGN )

Type 1: anti GBM or goodpasture syndrome

Type 2: immune complex mediated disease
Type 3 or pauci-immune: wagener
Type 4: Type 4 has features of both types 1 and 3. This is also
called "double-antibody" positive disease.

See the next page ...

RPGN can be classified into three types, based upon the

immunofluorescence patterns.
In type I RPGN, which accounts for approximately 20% of RPGN
cases, injury is caused by antibodies directed against the
glomerular basement membrane.
Type II RPGN accounts for roughly 25% of RPGN cases and is
characterized by the deposition of immune complexes in the
glomerulus.
The remainder of RPGN cases are type III, or pauci-immune
RPGN, which features antibodies directed against neutrophils
(anti-neutrophil cytoplasmic antibodies, ANCA).
Crescent formation

Type I
Accounting for approximately 20% of RPGN, type I RPGN is characterized by the presence
of autoantibodies directed against the glomerular basement membrane (GBM). It is also
called anti-GBM glomerulonephritis. The antibodies are directed against a particular protein
found in the GBM, type IV collagen, specifically the noncollagenous region of its 3 chain.
In addition to the anti-GBM antibodies, some cases of type I RPGN are also associated with
antibodies directed against the basement membrane of lung alveoli, producing Goodpasture
syndrome. The majority of type I disease, however, features anti-GBM antibodies alone;
these cases are considered idiopathic.
Type II
RPGN caused by the deposition of immune complexes accounts for 25% of RPGN and is
classified as type II. Thus any immune complex disease that involves the glomerulus may
progress to RPGN if severe enough. These diseases include systemic lupus erythematosus,
acute proliferative glomerulonephritis, Henoch-Schnlein purpura, and IgA nephropathy. While
polyarteritis nodosa also involves vasculitis associated immune complex deposition that can
lead to renal failure, it is not considered part of type-II RPGN because it mainly affects
medium sized vessels and does not necessarily involve the kidneys.
Type III
Also known as pauci-immune RPGN, type III RPGN accounts for 55% of RPGN and features
neither immune complex deposition nor anti-GBM antibodies. Instead, the glomeruli are
damaged in an undefined manner, perhaps through the activation of neutrophils in response
to anti-neutrophil cytoplasmic antibodies (ANCA). Type III RPGN may be isolated to the
glomerulus (primary, or idiopathic) or associated with a systemic disease (secondary). In most
cases of the latter, the systemic disease is an ANCA-associated vasculitis such as Wegener
granulomatosis, microscopic polyangiitis, or Churg-Strauss syndrome.
Classification of type III RPGN into primary or secondary may be unnecessary, as primary
type III RPGN and secondary type III RPGN may represent a spectrum of the same disease
process.
The ANCA form may have a more favorable response to treatment than other forms.
Type IV
Type 4 has features of both types 1 and 3. This is also called "double-antibody" positive
disease.

See the next page

Despite the wide variety of diseases that cause RPGN, all

types of RPGN are characterized by glomeruluar injury and
the formation of crescents. Severe injury and GBM rupture
leads to the leakage of plasma proteins through the GBM. Of
these proteins, fibrin is thought to contribute most strongly to
crescent formation. Epithelial cells lining the Bowman capsule
respond to the leaked fibrin and proliferate. Infiltrating white
blood cells such as monocytes and macrophages may also
proliferate. These proliferating cells surround and compress the
glomerulus, forming a crescent-shaped scar that is readily
visible on light microscopy of a renal biopsy.

Five "Ts" of congenital cyanotic heart disease:

1. Tetrology of fallot
2. Tricuspid atrasia
3. Transposition of great arteries
4. Truncus arteriosus
5. Total anomalous pulmonary venous return.

All of these are cutaneous or subcutaneous hges

Petechiae: less than 5 MM
Pupura: 0.51 CM
Ecchymosis: more than 1 CM

Hemeangiomas: UW:
Strawberry hemangioma ( infantile ) is the most common
benign vascular tumor in children. May regress spontaneously.
Cherry hemangioma most common benign vascular tumor in
adult.

Transferrin carrying iron in the blood

Apoferritin

Iron

Ferritin micelle

Hemosiderin

Macrophage in the bone marrow

Pulsus paradoxus is an important clue to cardiac tamponade. Pulsus

paradoxus is an exaggeration of the normal physiologic decrease in
blood pressure that occurs during inspiration. It is defined as a drop in
arterial blood pressure during inspiration of over 10 mmHg (a decrease
of less than 10 mmHg during inspiration is physiologic). Pulsus
paradoxus can be grossly diagnosed by palpating the radial pulse and
noting that it disappears during inspiration. A more accurate means of
diagnosis is done by blood pressure measurement with a
sphygmomanometer noting a decrease in arterial pressure greater than
10 mmHg during inspiration.

methylmalonyl-CoA

Succinyl CoA

Neurotoxic
CH3
B12
Active

Folic acid
CH3

Inactive

B12
Inactive
Folic acid
Active

Folic acid and methylmalonyl-CoA are competing for

B12. In megaloblastic anemia that is due to B12
deficiency, if the patient is given folic acid without B12,
the little of active B12 ( nonmethylated ) will be
consumed to activate folic acid ( demethylate ). As such,
methylmalonyl-CoA will built up, worsening the
neuropathy.

Metabolic acidosis
Increased anion gap:
MUD PILES
M- methanol
U- uremia
D- DKA
P- paraldehyde or phenformin
I- iron tablets or INH
L- lactic acidosis
E- ethylene glycol
S- salicylates

Sepsis
Shock
Hypoxia

Normal anion gap ( hyperchloremic metabolic acidosis )

HARD ASS
H- Hyperalimentation/Hyperventilation
A- Addison
No aldo. > decreased H excretion > HCL formation ( i.e. Cl retained ).
R- RTA
Differentiated by urine anion gap!
D- Diarrhea
A- acetozolamide
S- Spironolactone
S- saline infusion
P- pancreatic fistula
Uterosegmoidestomy ( segmoid dump bicarb in the ureter )

Winter's formula ....

Winter's formula ( AKA expected PaCO2 for MA ):

Is a formula to measure the adequacy of respiratory compensation
in cases of metabolic acidosis (specially in DKA cases)
PaCO2 = 1.5 ( measured bicarb ) + 8 +/- 2
Winter's formula gives an expected value for the patient's PCO2;
the patient's actual (measured) PCO2 is then compared to this.
If the two values correspond, respiratory compensation is
considered to be adequate.
If the measured PCO2 is higher than the calculated value, there is
also a primary respiratory acidosis.
If the measured PCO2 is lower than the calculated value, there is
also a primary respiratory alkalosis.
Example:
Patient with DKA and his bicarb is only 8, then his pCO2 should be
20 if it's higher than that then he's not adequately compensating
(respiratory fatigue or ensuing coma) then you need to think of
assisting his ventilation.

There are only four situations where disclosure of patient

information with out the consent of the patient is allowable.
1. When child, elder, or spousal abuse is suspected,
2. When a patient has sustained gunshot or stabbing injuries,
3. When a patient is diagnosed with a reportable communicable
disease and
4. When a patient threatens to kill or physically harm someone
else during their interaction with the physician and has a
reasonable ability to carry out this threat in the near future.
Reportable diseases:
AIDS ( but not HIV positivity )
Chicken pox
Hep A and B
Measles
Mumps
Rubella
Salmonella
Shigella
Syphilis
TB

Beta Lactam ring

Garage

House

Lactam ring
Its the garage that is always affected.

Bacterial genetics
Four ways by which bacteria can exchange genetic material:
1. Transformation
2. Transduction
3. Conjugation
4. Tranposon
# Transformation: one bacteria lysis, the others take pieces of its genome.
# Transduction: via bacteriophages. Two types of phages:
1. Virulent: invade the bacteria, replicate, kill the bacteria and pop out. As it does so, some
of the bacterial genetic material might get into one of these new phages and get
transduced into another bacteria.
2. Temperate phage: invade the bacteria, incorporate its DNA into the bacterial DNA and
wait as a prophage ( of course its DNA will be replicated with the bacterial DNA ). The
infected bacteria is termed lysogenic ( because it may lyse at any moment should the
repressor protein is damaged, for e.g. by UV light ). And the virus is called lysogenic
phage. Eventually, the prophage will be activated ( If the repressor protein, that prevent
the synthesis of virus specific proteins, is mutated ), the bacteria lyses and the phage is
released to infect another cell ( said to enter the lytic cycle or become lytic phage ).
The term lysogenic immunity is used describe the ability of the prophage ( the hidden
virus ) to prevent another phage form entering its cell.
Transduction has two types:
1. Generalized: virulent phages are involved in this
2. Specialized: temperate phages are involved in this. This occurs because the temperate
virus inserts itself only in predetermined area in the bacterial DNA. e.g. The lambda phage
of E. coli that inserts itself between the genes that are responsible for biotin and
galactose. If the cell turned into lytic cycle, one of these genes ( not both ) might get
packaged with one of the new phages and get into a new cell. The bacteria that get this
new gene would said to undergo lysogenic conversion ( see next page ).

Note: phage repressor is made by the bacteria to prevent the virus from producing its
structural protein. If the bacteria fail to produce this repressor, the virus will rapidly
produce the proteins that is in need of, assembles and lyse the cells ( lytic cycle instead
of lysogeinc cycle )

Lysogenic replication may result in lysogenic phage conversion, a change in the

phenotype of the bacteria as a result of limited expression of genes within a
prophage. This mechanism occurs in the following situations:
(1) In Salmonella polysaccharides as a result of infection with the epsilon
prophage.
(2) Conversion of nontoxigenic strains of Corynebacterium diphtheriae to toxinproducing strains.
(3) Conversion of nontoxigenic Clostridium botulinum types C and D to toxinproducing strains.

# Conjugation: direct transfer of DNA for cell ( F+ ) to cell

( F- ). The transferred DNA usually integrate into the new
bacterial plasmid and the recipient bacteria will become F+.
Rarely however, the transferred DNA incorporate itself into the
recipient bacterial DNA and the recipient bacterial will now
called HFr ( high frequency of recombination ). When excised,
this plasmid make contains within it a new genetic material, and
is called F' ( prime ).
# transposons: these are DNA pieces with legs! They could jump
to be inserted into a DNA of phage, plasmid and bacteria. When
they leave, they frequently take with them new piece of DNA to
a new bacteria.

Protein degradation mechanisms

1. Ubiquitin
2. Lysosomal degradation
3. Calcium dependent mechanism

Intermediate filaments

Sarcomas and some carcinomas

Carcinomas and some sarcomas

Mutated in progeria

Sensory Corpuscles
1. Pacinian: P for Pressure. Its for pressure and vibration, they
are deep seated in the joints and ligaments.
2. Meissner; as the way you say it, it's smoother that Merkle, so
meissner is for soft(light touch). Found on hairless (soft) skin
areas, palm sole, nipple, and tongue.
3. Merkle's; hard texture as the way you say it, so it's for harsh
touch or harsh edges, found at hard skin areas(hairy).
4. Anything else is free nerve ending and it's for pain and
temperature.

CHROMOSOME NOMENCLATURE (Figure 1-6)

1. A chromosome consists of two characteristic parts called arms. The short
arm is called the p (petit) arm and the long arm is called the q
(queue) arm.
2. The arms can be subdivided into regions (counting outward from the
centromere), subregions (bands), subbands (noted by the addition of a
decimal point), and sub-subbands.
3. For example, 6p21.34 is read as the short arm of chromosome 6, region 2,
and subregion (band) 1, subband 3, and sub-subband 4. This
is NOT read as the short arm of chromosome 6, twenty-one point thirtyfour.
4. In addition, locations on an arm can be referred to in anatomical terms:
proximal is closer to the centromere and distal is farther from the
centromere.
5. Figure 1-6 shows the G-banding pattern of a metaphase chromosome
along with the centromere, p arm, and q arm.

Collagen
Strong

Elastin
Stretchy

Proline, glycine, hydroxyproline

and hydroxylysine

Proline, glycine

Glycosylated

Nonglycosylated

Alpha chain triple helix

Tropoelastins that are held

together by fibrillin

Degerated by elastase
alpha antitrypsin inhibits
elastase.

4 transcription factors that are important in pleuripotential

stem cells:
Oct3/4
Sox2
c-MYC
Klf4
The most effective way to protect the life span is calorie
restriction. The mechanism is unknown but seems to be related to
a group of proteins known as Sirtuins.

Which amino acids are modified by the Golgi?

How are they modified?
> Asparagine: modifies the N-oligosaccharide
> Serine and threonine: addition of O-oligosaccharides

Post translational modifications:

1. Trimming
2. Covalent alternations:
i. Phosphorylation: occurs at OH group of Serine, Threonine and less
frequently Tyrosine( O-phosphorylation ). Phosphorylation is catalyzed by
kinases family of enzymes. This might leads to an increase of a decrease
in the activity of the protein.
ii. Glycosylation: addition of CHO side chain to a protein that is destined
to be a part of cell membrane or to go to lysosomes. It occurs at OH
group of Serine and Threonine amino acids ( O-glycosylation ) or the
nitrogen of amide group of Asparagine ( N-glycosylation ). E.g. Of such
CHO is mannose-6- phosphate that is added to enzymes that are destined
to be incorporated in the lysosomes. In collagen, glycosylation occurs in
lysine.
iii. Hydroxylation: occurs at proline and lysine AAs e.g. In collagen.
vi. Carboxylation: at glutamate, e.g. Vit K dependent carboxylation.
v. Addition of lipids such as farnesyl group.
Collagen post translational modifications occur in RER.
For all other proteins, all of the post translational modifications
occur in Golgi except N-acetylation.

Neurotransmitter
NE

Location of synthesis
Locus ceruleus, reticular formation
and solitary tract

The four Functional layers of the cerebrum:

1. The neocortex: the cortex itself
2. The limbic system: the instinctual part of our brain. Its used to be
considered as composed of: the amygdala, the hypocampus, the septum,
the parahypocamal gyrus, the dentate gyrus and the cingulate gyrus. Now
we know that the limbic system is far bigger than that. It might be
refereed to as archycortex.
3. The prefrontal cortex: inhibits the limbic system.
4. The fourth layer at which, all signals form the above layers get
summated into an actual effect. It composed of three layers:
A. The basal ganglia: summation of motor command
B. The thalamus
C. The hypothalamus.

Preoptic is not a
"true" hypothermic.
It belongs
developmentally to

Preoptic nuclei

telencephalon but

Optic tract
Optic chiasm

Tubular region ( situated

above the infundibulum )

functionally to
diencephalon. It
regulates the
parasympathetic NS.

Anterior -4

Middle -3

Posterior -2

Above downward:

Above downward:
Above downward:
1. Paraventricular: oxytocin
1. Dorsomedial nucleus: stimulates
1. Posterior
2. Anterior hypothalamic: cause the GIT results in obesity ( no as
hypothalamic:
body cooling ( AC ). Controls
important as ventromedial ).
cause body heating
the parasympathetic. Releases 2. Ventromedial nucleus: satiety
( PH ). Control
GnRH.
center ( feeding center is located
sympathetic NS.
3. Suprachiasmatic: circadian
in an area known as lateral
2. Mammillary
rhythm. See next page ...
hypothalamic zone ).
body: limbic
4. Supraoptic: ADH
3. Arcuate nucleus: regulates the
system.
ant. pit.
If you zap your lateral nucleus, you shrink laterally.
If you zap your ventromedial nucleus, you grow ventrally and medially.

See the next page ...

Ventromedial

Mediate satiety, destruction leads to hyperphagia

Stimulated by leptin

Lateral

Mediate hunger, destruction leads to anorexia

Inhibited by leptin

Anterior

Mediate heat dissipation via parasympathetic

Destruction leads to hyperthermia

Posterior

Mediate heat conservation via sympathetic

Destruction leads to hypothermia

Arcute

Secretion of dopamine ( inhibits prolactin ), growth

hormones releasing hormone, gonadotrophins.

Paraventricular

ADH, corticotropin releasing hormone secretion,

oxytocin and thyrotropin releasing hormone
secretion.

Supraotic

Secretion of ADH and oxytocin

Suprachiasmatic

Circadian rhythm and pineal gland gland

function.

Retina
Dark

Suprachiasmatic
NE release

Melatonin
Sleep

Pineal

Pharyngeal arches:
1st arch:

Ms: Meckeles cartilage, mandible, maleous,

Arch of Ms and Ts

mandibular ligament, muscles of mastication

( temporalis, masster, medial and lateral

Innervated by mandibular
and maxillary branches of

ptrygoids , myohyoid ).

the of the trigeminal CN.

Ts: tenser temponi, tenser veli palaini, anterior

Two Thirds of the Tongue.

Treacher Collins syndrome: 1st-arch neural crest fails to migrate

leading to mandibular hypoplasia, facial abnormalities.

2nd arch:
Arch of Ss
CN VII (facial
expression)
smile

Reichert's cartilage: Stapes, Styloid process, lesser

horn of hyoid, Stylohyoid ligament. Muscles of facial
expression, Stapedius, Stylohyoid, posterior belly of
digastric

3rd arch:
The word pharyngeal

4th and 6th arch:

Cricothyroid and larynx: the voice box.

Pituitary hormones that share common alpha unit are:

TSH
LH
FSH
Beta-hCH.

SHSH

Don't give beta blocker to patients with cocaine induced HTN, that would
worsen the BP.
Beta blockers are the DOC in patients with aortic dissection.

Cytokines
Hot

Bone stEAk

IL-1 fever
IL-2 stimulate T cells
IL-3 stimulate bone marrow
IL-4 IgE and IgG
IL-5 IgA and eosinophils
IL-6 an acute phase reactant, comes from macrophages ( like IL-1)
INF Alpha: an acute phase reactant, comes from macrophages.
Mediates septic shock.
IL-8: from macrophage. Major chemotactic factor ( the I in the
nemonic click.
IL-10: induces Th-2 and inhibits Th-1
IL-12: induces the differentiation of T cells into T helper 1 cells.
Activates macrophages
INF gamma: activates macrophages

Antiretroviral Side Effects

Bone marrow

Class effect
Rito
Indi-, Ataza-

Didano, zalcita, stavu.

Didano, Stavu
Abacavir

Class effect
Efavirenz
Efavirenz causes neuropsychiatric effects. Its teratogenic.

NRTIs
Protease inh.
NNRTIs

Zidoviudine
Zidovudine
Zidovudine
Zidu + lami

Protease inh.

HAART

Pharmacokinetics Equations

Clearance = Vd * Elimination constant ( elimination constant = 0.7/T half )

In maintenance, Vd is not a big deal.

MC

Css: concentration of steady state

Note: sometimes Vd and Cl in these equations will be divided by F
( bioavailability ). And unless the drug is taken orally, this F
equals to 100%, and that is why we didn't mention it here
because in these equations, the drug is taken IV.

Example Question ...

The 4 equations:
1. Vd= amount of given drug [IV]/
plasma concentration
2. Clearance= 0.7*Vd/T half
3. LD= Css*Vd
4. MD= Css*Clearance
T half= 0.7*Vd/ clearance
Given: clearance = 2L/hr
Vd= 0.5 L/kg*60 = 30 L
So T half = 0.7*30/2 = 10.5

LD= Css*Vd
LD= 20 mg/L * 30 L = 600 mg.

This 10 mg/L is the half of the previous target dose. So we have to wait
for one half to pass.

MD= Css* Cl
= 10 mg/L* 2L/hr
= 20 mg/hr

MD= Css* Cl
LD= Css* Vd
Obviously, only MD is affected by clearance. It should be
decreased.

Gram -ve rots

Mackoncky
Lactose fermentors

Non fermentor
Oxidase test

Fermentation speed
Positive

Negative
Fast fermentors

P. arginosa
Slow fermentors

E. coli
Klebsiella
Enterobactor

Serratia
Citrobacter
TSI Test
H2S
No H2S
Shigella

Proteus
Salmonella

Physiologic intervention

Intensity of heart murmur

Respiration

Right-sided murmurs increase with inspiration

Left-sided murmurs increase with expiration

Valsalva
Standing

Most murmurs diminish except HOCM and MVP

Squatting
Passive leg raising

Most murmurs become louder except HOCM and

MVP
Increased venus return helps the large, oversized mitral valve
leaflets to close properly.
Note: squatting increases both preload and afterload

Handgrip

Murmurs of MR, VSD and AR become louder

Murmurs of HCM decreases

GnRH

LH

FSH

Inhibin B, inhibits beta subunit of FSH

Testosterone
Inhibits beta
subunit of LH and
that of GnRH

Semenepherous tubule
containing Sertoli cell
Laydig

Basal Ganglia

Antipsychotics (neuropleptics)
High potency - "Try to Fly High"
Trifluoperazine, Fluphenazine, Haloperidol
(extrapyramidal signs)
Low potency - "Cheating Thieves"
Chlorpromazine, Thioridazine
(non-neurologic SEs: anticholinergic, antihistamine, alpha blockade)

dsDNA fracture

X and gamma rays

Pyrimidine-pyrimidine Ultraviolet
dimers

Homologues or non
homologues religation
Ultraviolet specific endonuclease
that causes nick at the damaged
site that are later excised by the
5'-3' exconuclease activity of DNA
polymerase.

Deamination

Spontaneously or
chemical

Base excision repair

Streptococci

Alpha hemolytic

Beta hemolytic

Optochin

Bacitracin

Sensitive

Resistant

S. pneumina

Viridans

Ps are sensitive

Gamma hemolytic

Sensitive

Resistant

S. pyogen

Agalactiae

Grow in bile
AND 6.5 NaCl
Enetrococci ( E. feacium )

Grow in bile BUT

NOT in 6.5 NaCl
Non enterococcus S.
Bovis

Class 1 antiarrythmia

Class 1A: Double Quarter Ponders:

Dipyridamole, Quinidine, Procianamide
Class 1B: Lidocaine, Tocanide, Mexiletine
Class 1C: More Fries Please:
Moricizine, Flecainide, Propafenone

Virion
CMV

EBV

HIV

Rabies

Rhinovirus

Cellular receptor
Cellular integrins
CR2 ( CD 21 )

CD4 and CXCR4/CCR5

N and M receptors

ICAM1 ( CD56 )

Temporal: sequential impulses form the same neuron,

Spacial: simultaneous impulses form the different neurons.

Activation of nucleoside analog drugs

Viral Dependent Nucleosides
Acyclovir
Ganciclovir
Famciclovir
Valacyclovir

Viral Kinase ( to attach the first phosphate )

Nucleotides:
Cidofovir
Tenofovir

Host cell Kinases

Activated nucleotides

> Inhibit DNA

Cell dependent nucleosides:

Zidovudine
Lamivudine

polymerase
> Cause chain
termination.

Viral Genetics
Reassortment: two segmented viruses. These are Arena, Bunya, Orthomyxo ( like
the ABO system ) and Reo. ( 2,3,11,8 segments respectively ).
Recombination:
Occurs in non-fragmented viruses. There would be an exchange in genomic
material between two chromosome via crossing over within homologous region .
Transformation: generally defined as the uptake of naked DNA by a prokaryotic or
eukaryotic cell. In virology, used to describe the incorporation of viral DNA into a
host cell chromosome.
Phenotypic mixing: just the nucleocapsid acquisition. No genomic exchange so no
new cytopathic features.
Interfering: one virus inhibits the replication and/or the release of the other
virus. No genomic exchange.

Blotting Technique
DNA

RNA

Proteins

Proteins that binds to DNA such

as transcription factor, steroids,
vitamin D receptors, thyroid
proteins, etc.

Secretory
Cell membrane
Etc

Metabolites

Folate antagonist

Methotrexate

Purine analogues

6-Thiopurines ( 6-MP, 6-GP )

Fludarabine- CLL
Cladrebine- HCL

Pyrimidine analogues

5-flurauracil
Cytarabine and
other 'abine'
members.

Pathophysiology Of SIADH
Excessive ADH secretion
Water retention

Increased total body water

Transient, SUBCLINICAL,
extracellular volume expansion
Decreased aldosterone and
increased ANF.

Dilutional hyponatremia

Increased urinary Na excretion

Further Na loss

Euvolemic hyponatremia

Normalization
of extracellular
fluid volume.

Glucose Transporters
Characteristics feature
GLUT1

RBCs, CNS

Basal glucose transport

GLUT2

Liver, Pancreas

Regulation of insulin release

GLUT3

Placenta, brain, kindeny

Placental glucose transport

GLUT4

Adipose, skeletal muscles

Insulin mediated glucose uptake

GLUT5

Sperms, GIT

Fructose transport

Hemangiomas
These are two types: Capillary and cavernous hemangiomas
Capillary hemangiomas are :
Strawberry hemangioma
Cherry hemangioma
Nevus flammeus ( aka port-wine stain )
Pyogenic granuloma
# Strawberry hemangioma ( infantile, juvenile, premature ):
Appear since birth
Regress spontaneously
Bright red when in the epidermis, when deeper they are more violaceous.
# Cherry hemangioma ( senile )
Benign capillary hemangioma of the elderly.
Does not regress.
Frequency increases with age
Cutaneous and not found in mucosa and deep tissues
# Nevus flammeus ( aka port-wine stain ):
Mature capillaries.
Sharply demarcated, irregular, flat patch that commmonly involves
the face.
Associated with Sturge-Weber disease
Fleshed colored ones regress, discolored ones persist
# Cavernous:
Dilated vascular spaces with thin-walled endothelial cells
Blue, large compressible masses
Less likely to regress
Associated with VHL
Could occur in the mucosa or deep tissues.

Pharyngeal and Aortic Arches

Associated nerve

Key Aortic arch derivative

Trigeminal

Maxillary artery ( portion )

Facial

Stapedial artery ( regresses )

Glossophayrngeal

Common carotid and prox. internal

PA

AA

Superior laryngeal
( vagus )
Obliterated
Recurrent laryngeal
( vagus )

carotid
True aortic arch and subclavian
artery
Obliterated
Pulmonary artery and ductus
arteriosus.

See the next page ...

Embryology of the heart

The smooth part of the RA comes from

the right horn of sinus venosus. The left
horn gives rise to coronary sinus ( the
green circle ).
SVC comes from rt
common cardinal

Aorta and pulmonary artery come

from truncus arteriosus
Smooth part of the LA is
from pulmonary veins

vein and rt anterior

cardinal vein.

Trabiculated parts comes

from primitive chambers.

The smooth part of the both

ventricles comes form bulbus
cordis.

Cardiac tissue conduction velocity

Park At Ventura Avenue
Fastest

Purkinje System

Atrial Muscle

Ventricular Muscle

Slowest

AV Node

Lipid Lowering
High LDL

Hypertriglyceridemia

Low HDL

Diet and Exercise

Still low

Still high

Still high

Statin

Still high

Ezitamibe

Fibrates

Still high

Niacin

Niacin

Relative risk reduction is the percent reduction in the

absolute risk.
Absolute risk
Control

Minus

Absolute risk

Treatment

Absolute risk

Control

NNH = 1/ ARI
NNT = 1/ ARR
ARI = Event rate of treatment - event rate of control
ARR ( AR ) = Event rate of control - event rate of treatment

"Happy Cat Tom Took Pie To Little Sister":

Hamate Hamate has a Hook
Capitate
Trapezoid
Trapezium: thumb swings on the trapezium!
Pisiform
Triquital
Lunate: the more medial of the 2 bones that articulate with the radius
Scaphoid: the more lateral of the 2 bones that articulate with the
radius
Injuries that cause lunate dislocation also cause # of the scaphoid. Avascluar necrosis is
a late sequel.

Anti mycobacterial drugs resistance:

INH:

Decrease the expression of the enzyme

catalase perioxidase; the enzyme that activates
the drug

Rifampin

Mutation is the gene that code for the enzyme

DNA-dependent RNA polymerase

Ethambutol

Increases the production of the enzyme

arabinosyl transferase, an enzyme that
participate in cell wall synthesis

Pyrazinamide

Decreased synthesis of the enzyme

pyrazinamidase that convert the drug into an
acid that suppose to decrease the PH within
the bacterium.

Streptomycin

Modification of 30S subunit.

Bacterial Toxins
# Both shiga toxin and cholera toxin are encoded by bacterial
chromosomes (Chromosomal Encoded Somethings = Cholera,
Endotoxin, Shiga toxin )
# Phage coded toxins pnemonic is OBED:
O Ag of salmonella
Botulinum toxin
Erythrogenic toxin of S. pyogens
Diphtheria toxin
Shiga-like toxin
# Other toxins and Multiple drug resistance -- Plasmid

Skull openings:

Cleaners Only Spray Smelly Stuff Right On Smelly Idiots In

J. Jonah Jameson High
for Cribriform plate (Olfactory), Optic canal (Optic),
Superior Orbital Fissure (Oculomotor), Superior Orbital
Fissure (Trochlear), Superior Orbital Fissure (Trigeminal Ophthalmic), Foramen Rotundum (Trigeminal - Maxillary),
Foramen Ovale (Trigeminal - Mandibular), Superior Orbital
Fissure (Abducens), Internal Acoustic Meatus (Facial),
Internal Acoustic Meatus (Vestibulocochlear), Jugular
Foramen (Glossopharyngeal), Jugular Foramen (Vagus),
Jugular Foramen (Accessory), Hypoglossal Canal
(Hypoglossal)
RoMax
OMan

Skull openings:
Cribriform plate

Olfactory

Optic canal

Optic nerve

Superior Orbital Fissure

Nerve for the extra Ocular
muscles

Oculomotor
Trochlear
Trigeminal - Ophthalmic
Abducens

Foramen Rotundum
RoMax

Trigeminal - Maxillary

Foramen Ovale
OMan

Trigeminal - Mandibular

Internal Acoustic Meatus

Facial
Vestibulocochlear

Jugular Foramen

Glossopharyngeal
Vagus
Accessory

Hypoglossal

Hypoglossal Canal

UWorld Test Results

Histology
Biostatistics
Anatomy
Bio
Genetics
Pathophysiology
Physiology
Pharm
BS
micro
Pathology
Immuno
Over all cumulative performance is 77%

63
68
70
71
71
72
72
77
80
82
82
90

Biofilm producing bugs

Staph. epidermitis
Strept. sangus and mutants
Viridant group
Pseudomonas
Nontypable H. influenzae

Quad Screening Test

Down

Edward

Patau

AFP

Normal

B-hCG

Normal

Estriole
Inhibin

Normal
Normal

Normal

Thalamus

General and gustatory

sensation from head
and neck [ trigeminal
and gustatory ]
General sensations
from whole of the
body except the
head and neck
[ spinothalamic and
medial leminscus ].

VPL
Cortex:
BM area
1,2,3
VPM
Visual sensations: LGB
Auditory sensations: MGB
So, all sensations relay in
the cortex except smelling.

Dopamine Agonists

Ergot Componds
Bromocriptine
Pergolide

Non-ergot Compounds
Pramipexole
Ropinerole

DNA repair mechanisms

Single stranded
1. Mismatch excision repair: to repair errors that results form DNA
synthesis after the proofreading has failed.
Defective in Lynch syndrome.
2. Base excision repair: to repair erroneous bases in the DNA ( e.g.
Uracil ) that usually occur spontaneously by deamination or
exposure to some chemicals.
3. Nucleotide excision repair: to repair purine/pyrimidine dimers
that usually results from exposure uV radiation.
Defective in XP.

Double stranded

4. End joining repair mechanism: repair breaking in dsDNA that

usually results from exposure to ionizing radiation. The mechanism
here is low yield. These patients are very sensitive to radiation
( such as x-ray ). End joining is used during VDJ that used by B
cell to make antibodies and T cell to make TCRs, as such, patients
deficient in these enzymes used to mediate repair of end joining
may suffer from SCID.
See next pages ...

Nucleotide Excision Repair

Pyrimidine dimer
A three-subunit endonuclease made up of the proteins UvrA,B and
C, excise a patch of 12-13 nucleotides spanning the dimer.
1. UvrA complexes with UvrB and the complex utilizes ATP. UvrA
recocnizes the damaged area and the complex binds to it. UvrA
bends the damaged area and loads UvrB in the bend and it then
get released.
2. Then UvrC is loaded and it nicks
the damaged DNA strand at two
sides flanking the damaged area

3. Another complex called UvrD

helicase strips the short damaged
segment.

UvrB

Nick

UvrC

4. The DNA polymerase fills the

gap and DNA ligase seals the
remaining gap.
See next page for base
excision repair.

Base excision repair

Certain bases are not supposed to occur in DNA such as uracil
( cytosine deamination gives uracil). This will have a mitogenic
effect; because while C base pairs with G, U base pairs with A.
Adenine
Guanine
Cytosine

Deamination

Xanthine
Hypoxanthine
Uracil

All these are examples of wrong

bases that could be found in the
DNA.

Glycosylase break the bond the connects the defective base

with the dexoyribose on the phosphodiester backbone, creating
an area without a base ( apurinated/apyrimidnated site ).
The released base
Glycosylase

3'

AP endonuclease cleaves the 5' end of the

AP site before a lyase cleaves the 3' end.

5'

Deoxyribose AP site

3'

5'

DNA polymerase fills the gap and a ligase seals the nick.
Mismatch repair system ...

Mismatch repair system

Mismatched nucleotides are firstly repaired by the proofreading
activity of DNA-polymerase delta and epsilon. When this fails,
this mismatch repair system comes to play. It involves several
genes including MSH2 and MLH1 which codes for components of
human MutS and MutL homologs. Mutations in these two genes
account for around 90% of cases of Lynch syndrome.
1. MutS detects the mismatching in the new strand
3'
( which is characterized by occasional nicks on
the phosphodiester bond ).

2. MutL is then recruited and the complex

then slides along the DNA until it find a neck.
3. Exonuclease 1 is then binds to the complex
and it starts to degrade the new strand toward
the 3' end past the mismatched point, leaving a
variable gap. The single DNA strand is stabilized
by ssDNA binding proteins.

4. The gap is then filed with DNA polymerase delta and the nick is
sealed with ligase.

5'

Inherited disorders in DNA repair mechanisms:

1. Ataxia Telangectasia:

DNA hypersensitivity to ionizing radiation.

2. XP:

DNA is hypersensitive to UV

3. Fanconi anemia:

DNA is hypersensitive to cross-linking

agents.

4. Bloom Syndrome:

Generalized chromosomal instability

5. HNPCC:

Defect in DNA miss-match repair enzymes.

Atheroma Formation
Intimal injury ( say by HTN or DM ) leads to expression of vWF by
endothelial cells. vWF traps platelets leading to platelets plug
formation and WBC recruitment.
Also LDLs might get beneath the basement membrane of the tunica
intima worsening the inflammation that has begun with platelet.
Continued LDL deposition leads to fatty streak formation.
Macrophages engulf the LDL and become foam cells.
Injured endothelium release growth factors that promotes smooth
muscle cells ( SMC ) migration and proliferation such as PDGF. These
SMC are responsible for intimal thickening by producing collagen,
elastin and proteoglycans.

Mnemonic for class I antiarrythmics

Police Department Questioned The Little Man For Pushing Ecstasy!

# Police Department Questioned (Class IA):

Procainamide, Disopyramide, Quinidine
# The Little Man (Class IB):
Tocainide, Lidocaine, Mexiletine
# For Pushing Ecstasy (Class IC):
Flecainide, Propafenone, Encainide.

Work of Breathing
Minute ventilation= tidal volume*RR
When the elasticity of the lung is increased most of work is done during
inhalation. And the larger the tidal volume the patient takes, the 'bigger'
the work he is going to exert. As such, patients with restrictive lung
diseases tends to decrease the tidal volume. And to maintain the same
minute ventilation, the tends to increase the RR.
In obstructive diseases, most of the work is done during expiration. And
as the patient increases his RR, more and more work is exerted. As such,
these patients tend to decrease the RR and increase the tidal volume
( to maintain the same minute ventilation ).
Work of breathing
The least work

RR

15
Normal

10
Obstructive:
Slow, deep.

20
Restrictive:
Rapid, shallow

Antihistamines
First generation:
Anti-H1, anti-M, anti-serotonergic and alpha adrenergic. They are
lipophilic and as such, the could cross the BBB.
You must first chant "dimen, diphen, chlorphen" before you fall
asleep: dimenhydrinate, diphenhydramine, chlorpheniramine. These
are more sedating.
Added to these are promethazine and meclizine.
Second generation: devoid of anti-M, anti-serotonergic and alpha
adrenergic properties. They cant cross the BBB and are less
sedating: Don't Let u Fall aSleep
Desloratadine, loratadine, fexofenadine, cetirizine.

Sarcomere Anatomy
Zoe Is A Horny Mama!

Parts of the sarcomere correspond to the following mnemonic:

Zoe (Z-line)
Is (I-band)
A (A-band)
Horny (H-line)
Mama! (M-line)
Additionally, the light and dark bands are isotropic and anisotropic. The second
letter of each word corresponds to the band name and its properties.
dArk (A-band, anisotropic)
lIght (I-band, isotropic)

Effects Of Glucocorticoids

Liver:
Increase proteins
synthesis, esp. those of
gluconeogenesis and
glycogen synthesis .
Peripherally, they
antagonize the effect of
insulin leading to
increased catabolism of
adipose and muscular
tissues.

Bone:
Decrease bone density by
Inhibiting GI Ca absorption
Increase renal Ca excretion.
Inhibit bone forming
activity of osteoblast.

Immune system:
Decrease lymphocyte count
especially CD4.
Decrease eosinophils
Increase neutrophils

Skin:
Inhibits fibroblast
proliferation and collagen
formation leading to
thinning of the skin.

Esophagitis
Endoscopic findings
Candida

Herpes

CMV

Microscopic finding

Patches of grey/white
pseudomembranes on
erythematous background.

Yeast cells and

pseudohyphe that invade
mucosal cells

Small vesicles that evolve

into punched out uclers

Eosinophilic intranuclear
inclusions ( Cowdry type
A ) in multinuclear giant
cells at the margin of
the ulcer.

Linear
ulcerations

Both intranuclear and cytoplasmic

inclusions

Torsade

Torsades is usually produced by antiarrhythmic drugs that

prolong the QT interval which include class 1 and some class 3
antiarrhtymic's.
1)Quinidine, procainamide,Disopyramide which are class 1 drugs.
2)Ibutilide, dofetilide,sotalol the class 3 drugs.
3) Amidarone is the a combination Class1 and class 3 drug and it
does prolong the QT interval but it is least likely to cause
Torsades or any New arrhythmias. The reason Given is that,
Torsades blocks Ca channels and Beta receptors and sodium and
patassium channels.

Benzos
BZ 1 receptor - for SEDATION therefore Sleep disorders = Temazepam &
Oxazepam. (Mnemonic I use is "go TO sleep")
BZ 2 receptor - for anxiolysis therefore Anxiety disorders = Lorazepam,
Diazepam, Midazolam and Alprazolam.
Diazepam is the longest acting (24 to 36 hours).
Midazolam is shortest acting (4 hours, therefore its used in pre-op induction
anesthesia)
Oxazepam, Temazepam & Lorazepam are metabolized Outside The Liver. (OTL)
Also, they increase the frequency of opening of Cl- channels as compared to
Barbiturates which increase the duration.

# Long acting: Chloro Floro Carbon Drugs

Chlorazepate, Flurazepam, Chlordiazepoxide, Diazepam.
# Intermediate acting: LATE
Lorazepam, Alprazolam,Temazepam, Estazolam.
# Short acting: TOM
Triazolam, Oxazepam, Medazolam.

Mechanisms of HCC in HBV infected liver

Viral HBx protein

HBV

Activates the synthesis

of IGF-II and increase
the receptors of IGF-I

P53 inactivation
Cellular proliferation

Other mutations as
a result of chronic
inflammation.

The amino acids with 3 titrable protons are:

# The basic (HLA) ones- Histidine, Lysine, Arginine
# The acidic ones - aspartate, glutamate
# Just 2 more: cysteine and tyrosine

"acidic basic CT"

In PCOS, LH is increased increasing androgens and FSH is decreased with resultant build
up of androgen leading to many of the features of the syndrome, e.g. Hirsutism.

LH

Progesterone
Androgens

Cholestrol
Theca interna
Androgen synthesis

Testosterone

FSH

Granulosa

Estrogen
Estradiol

Contain aromatase

Granulosa

Theca externa
( fibrous capsule )

Theca interna

Alzheimer

Early ( < 60 yrs )

Associated with the following 3
mutations:
1. Amyloid precursor protein on
chromosome 21
2. Presenilin 1 gene on
chromosome 14.
3. Presenilin 2 gene on
chromosome 1.

Late
Assocaited with epsilon 4
allele of Epolipoprotein E4.

Drugs ( Nitrites )

Fe2+
( e.g. in Hb )

Fe3+
( MetHb )

Binds tightly to cyanide

Causes dusky discoloration
Can't carry O2

Effect of hyperammonemia on glutamine-glutamate cycle

NH4

Astrocyte
Accumulate and
cause damage

Glutamine DH

Glutamine
Glutaminase

Glutamate

Glutamine
Glutamine
synthase

Alpha KG

TCA
Glutamate

NH4

NMDA

AMPA

Hyper NH4 affects the brain in two ways: 1. Neuron are affected because excess
ammonia favor the formation of glutamate depleting the cell from alpha KG, an
important substrate for TCA. 2. Glutamine built within the astrocytes a toxic
levels.

Fen-phen
Fenfluramie and phentermine are appetite suppressant drugs
that causes pulmonary hypertension and cardiac valvular
problems.

Vitamin D
7-dehydrocholesterol
( Provitamin D3 )

UV light ( 290-350 )

Previtamin D3
Isomerization induced by heat

Cholecalciferol

D2 ( Plant derived )

( Vitamin D3 )

25-hydroxycholecalciferol

( cytochrome enzyme 25-hydroxylase of the Liver )

1,25 dihydroycholecalciferol
1 alpha hydroxylase in the
kidney.

24,24 dihydroycholecalciferol
Biologically inactive made when
there is 1,25
dihydroycholecalciferol excess.

PTH

Proopiommelanocortin
POMC a polypeptide!

beta-Endorphins

ACTH

MSH

Polyol Pathway

Glucose
Aldose
reductase
NADPH

Glycolysis

NADP

Sorbitol

Sorbitol
dehydrogenase
NAD

NADH

Fructose

Active factor X

Inactive factor X

Unfractionated heparin
PLUS
Antithrombin
Thrombin

Inactive thrombin

Active factor X
LMWH
Plus

Inactive factor X

Antithrombin
LMWH only inactivate because due to its short length, that
renders it unable to bind to thrombin.

GnRH

Hypothalamus

GnRH agonists:
Leuprolide
Goserelin
Nafarelin

LH

Ant. Pit

They decrease LH and

Leydig cell stimulation.

Testosterone

Ketoconazole

Leydig cell

Cholesterol

Spironolactone

DHT

Peripheral tissue

Androgen-receptor
complex in target cell

Desomlase

Pregnenolone

Finasteride

Flutamide
Cyproterone

Nuclear receptors
Thyroid hormones
Retinoids
Perioxisomal proliferating activated receptors
Fatty acids

Hereditary Angioedema: C1 esterase inhibitor deficiency

C1 esterase inhibitor

Kallikrein

Kininogen

Plasminogen

Plasmin

Bradykinin

ACE
inhibitors

ACE

Inactive
products

Increased vascular permeability

Fibrin

Fibrin split products

C1 C1 esterase

Activated C1

C1 esterase inhibitor

Angioedema

Time line
0-4 hr
4-12 hrs
12-24 hrs
1-5 days

5-10 days

10-14 days

2 wks to 2
months

MI
Minimal changes
Early coagulation necrosis,
edema, hemorrhage and wavy
fibers.

CVA

12-48 hrs: red neurons

( eosinophilic cytoplasm,
pyknotic nucleus, loss of
nissel substance )

Coagulation necrosis

Coagulation necrosis and

neutrophilic infiltrate
Macrophage infiltration
Granulation tissue and
neovasculrization
Collagen deposition and
scar formation.

24-72 hrs : necrosis with

neutrophilic infiltration
3-5 days: macrophages
infiltration and phagocytosis

7-14 days: reactive gliosis

and vascular proliferation
around necrotic area
> 2 weaks: glial scar.

Auto-antibodies

Anti-SM = Anti-Smith = Anti small nuclear ribonucleoproteins ( snRNPs ).

Hurtnup Vs Fanconi
In hurtnup, there is aminoacidouria restricted to neutral amino acids.
This urinary excretion of proline, hydroxyproline and araginine remains
unchanged. This in contrast to Fanconi, in which there is generalized
aminoacidouria.

Monitoring of osteoblasts and osteoclasts activity

# Osteoblast activity is monitored by alkaline phosphatase.

# alkaline phosphtase of the bone could be differentiated from
that of the liver by the fact that alk. phos. of the bone is
denaturable by heat and that of the liver is not ( bone boils ).

# Urinary hydroxyproline and deoxypyradinoline are used to

monitor osteoclastic activity.

C. Difficile has two toxins: A & B

1. A toxin which is a neutrophil chemoattractant that cause
inflammation, leading to loss of H2O in the lumen of the bowel ( D )
and enterocytes death.
2. B toxin: causes actin depolymerization, loss of cellular cytoskeleton
and cellular death ( necrosis ).

Smocking cessation is the single most important modifier of mortality

including aspirin therapy and tight glycemic control.
Note: the role of tight glycemic control in reducing cardiovascular
mortality is not proved yet.

Process of T-cell Maturation

TCR rearrangement
+ve selection
T-cell linage committed precursor
Negative for all of TCR, CD3, CD4,
and CD8 ( double negative )

-ve selection

Subcaspular zone
Positive for all of TCR,
CD3, CD4, and CD8
( double positive )

Cortex

Aptosis

Positive selection by cortical epithelial cells

Insufficient
affinity for self
MHC

Positive
Medulla for CD4,
CD3 and
TCR

Sufficient affinity for self MHC

Positive
for CD3,
CD8 and
TCR.
Negative selection by medullary epithelial cells

Negative selection by medullary epithelial cells

No excessive affinity
Survival

Excessive affinity
for MHC
Aptosis

No excessive affinity

Survival

Minors Consents

Minors can consent to Rx for ( no parents consent required ):

1. Pregnancy
2. STDs
3. Birth control
4. Drug or alcohol addiction.

Pyrimidine Synthesis: Oratic Aciduria

NH4+CO2+2ATPS

Rx of oratic aciduria is via

uridine supplementation. This
uridine is converted to UMP via
nucleoside kinases. UMP
inhibits CPS-2 and decrease
oratic acid production.

CPS-2
Carbomyl-P

Deficiency leads to
oratic aciduria

Oratic acid
White crystals appear in urine

PRPP Oratate Phosphoribosyl transferase

Hydroxyurea

UMP
Ribonucleotide
reductase

dUMP
CH3
Thymidylate
Synthestase

dTMP
5FU
5-deoxyuridine

CMP
NH2

dCMP
Ribonucleotide
reductase

Hydroxyurea

Cutaneous lymph drainage from umbilicus to feet, including

the external genitalia and anal canal up to the dentate line
drain into superficial Inguinal lymph nodes. Exceptions being:
Testis ( paraortic lymph nodes )
Glans penis and skin of the posterior calf ( deep inguinal ).

Pentostatin is an anticancer that inhibits the enzyme adenosine

deaminase.
Cladribine is a cytotoxic purine analogue that is resistant to
degradation by adenosine deaminase.

Bacterial vaginosis
( MCC of vaginitis )

Signs and Sx

Thin, off-white
discharge with
fishy odor.
No inflammation

Candida
Vluvovaginits
Trichomoniasis
( 2nd MCC of vaginitis )
Malodorous, graygreen, thin, frothy
vaginal discharge
Inflammation

Laboratory test/
microscopy

PH> 4.5
Clue cell
Positive whiff test
( amine odor with
addition of KOH )

PH> 4.5
Motile trichonads

First line Rx

Mitronidazole

Mitronidazole or
tinadazole
Must Rx sexual
partner

2nd line Rx

Clindamycin

None

Thick, white
discharge that
adherent to vaginal
wall.
Inflamed
Normal PH
( 3.8-4.2 )
Pseudohyphae

Fluconazole

OTC creams such

as clotrimazole and
miconazole

Polythysemia Vera
EPO receptor

EPO

Janus kinase -2
STAT

Translocate to nucleus,
control proliferation of
myeloprogintor cell

Mutated Janus
Kinase -2,
phosphorylated
without EPO.

Important Amino Acids Derivatives

Phenylalanine --(phenylalanine hydroxylase)--> Tyrosine -->(Tyrosine
hydroxylase) --> DOPA --(DOPA decarboxylase)--> Dopamine
Glutamate --(glutamate decarboxylase)--> GABA
Glutamate ---> Glutathione
Glycine + Succinyl Co A ----> Heme
Glycine + Arginine + SAM ---> Creatine
Glutamate + Aspartate ---> Pyrimidines
Glutamate + Aspartate + Glycine ---> Purines
Glycine + Proline ---> Elastin
Arginine ---> Nitric Oxide
Argnine + Aspartate ---> Urea
Histidine ---> Histamine
Tryptophan ---> Serotonin
Tryptophan ---> Melatonin
Tryptophan ---> Niacin
Tyrosine ---> Thyroxine, Melanin

Neural Control of ventilation

Sleep apnea

Upon exposutre to PTH,

osteoblasts incrause their
production of RANK L and MCSF,
which in turn, act on monocyte
and activate them to
differentiate into osteoclasts.

PTH receptor
Vitamin D receptor
Osteoblast

RNAK ligand
Osteoprotegerin
Osteoprotegerin is a protein
secreted from mesenchymal cells
and acts as a decoy receptor,
decreasing the interaction
between the RANK L and its
receptor, inhibiting monocytes
maturation into osteoclasts.

Monocyte colony
stimulating factor
( MCSF )
Monocyte
MCSF and RANK L
stimulate monocytes to
mature into osteoclast.
Calcitonin receptor, the
only receptor on
osteoclasts. It inhibits
osteoclasts.

Osteoclast
The ratio between RANK L: OPG determines bone turn over. Higher ratio leads to bone
resorption. RANK receptors are over expressed in hypoestrogenic states, accelerating
bone turn over.
A decoy receptor, or sink receptor, is a receptor that binds a ligand, inhibiting it from
binding to its normal receptor. Etanercept is another example of a decoy receptor.
See next page for VitD

Vit. D receotor

Vit. D

Osteoblast

Alkaline phosphatase
Alkaline phosphatase makes the appropriate
solubility product to mineralize cartilage and
bone.

Note: PTH is more involved in maintaining Ca levels in our blood ( so its

understandable that is increases Ca absorption and decrease Phosphorous
absorption to decrease the solubility factor ), while Vit D is more involved
in mineralizing our bones and cartilage, so increases both Ca and Ph
absorption to increase the solubility factor mineralizing osteoids.

Blood supply to ureters

Zone I: periportal zone:

Affected lst by viral hepatitis. Glycogen and protein systhesis
Zone II: intermediate zone. Yellow fever and Councilman bodies ( a
hepatocyte under going aptosis ).
Zone III: pericentral vein (centrilobular) zone:
Affected lst by ischemia
Contains P-450 system
Most sensitive to toxic injury
Site of alcoholic hepatitis
lipids, drugs and alcohol metabolism.

Leucovorin with methotrexate and 5-FU

Leucovorin rescue normal cells after methotrexate administration. It
enhances tne toxicity of 5-FU because it helps it to form an irreversible
complex with the enzyme thymdylate synthase, decreasing the amount of
Ts that are available.

Sympathetic Stimulation on beta cell

Beta stimulation
increase insulin
secretion.

Alpha stimulation
inhibits insulin
secretion.

Beta cell
Insulin

Beta brings!

Nuclear Receptors
1-Retinoid receptor (Vit A)
2-Calcitriol receptor (Vit D3)
3-T4/T3 (T3 binds more avidly)
4-Fatty Acids bind to PPAR
5-PPAR -alpha (Fibrates)
6-PPAR -gamma(Thiozolidinedions)

Cytoplasmic receptors
1. Androgen
2. Estrogen
3. Progestins
4-Glucocorticoids (e.g Cortisol)
5-Mineralcorticoids (e.g Aldosterone)

Think adrenal hormones

Maple Syrup Urine Disease

Leucine

Neurotoxicity

Isoleucine

The distinctive sweet odor

Valine

Malformation Primary defect in a cell or tissue [ the defect is intrinsic ]

Deformation

Structural defects due to extrinsic mechanical forces. E.g. Hip

dislocation secondary to breach presentation.

Disruption

Secondary break down of a previously normal tissue. E.g.

Limb amputations due to amniotic bands

Sequence

Just remember Porter syndrome

Agensis

Complete absence of an organ.

Ulcer Vs Erosion
Ulcer

Erosion
Mucosa
Musclaris mucosa
Submucosa
Muscularis propria
Serosa

Causes of lactic acidosis

Enhanced metabolic rate: seizure and exercise
Reduced oxygen delivery: shock
Diminished lactate metabolism: liver failure and hypo-perfusion
Decreased oxygen utilization: cyanide poisoning
Enzymatic defects in glycolysis and gluconeogenesis

Drugs That Cause Seizure

Burpropion
Isoniazid
Imiprnem

Neuronal reaction to injury

Type of response
Acute injury
[ red neuron ]

Axonal reaction

Neuronal atrophy

Type of injury
Transient severe insult that
lead to cell death

Loss of axons

Progressive degenerative
disease

Histologic change
Shrinkage of the cell body
Pyknosis
Loss of Nissl substance
Eosinophilic cytoplasm

Enlargement of the cell

body
Eccentric nucleus
Enlargement of the
nucleolus
Dispersion of Nissl
substance

Loss of neurons
Reactive gliosis

Xanthomas
Typically associated with hyperlipidemia and
lymphoproliferative malignacies
1. Eruptive Xanthomas: hypertriglycerides
2. Tuberous and 3. Tendinous Xanthomas
4. Plane Xanthomas: in skin folds. Associated with PBC
5. Xanthelasma: no associated lipid abnormality in 50% of the
affected individual.

Drugs used to Rx MRSA

Vancomycin

Blocks glycopeptide
polymerization by binding
tightly to D-alanyl-D-alanine

Damptomycin Depolarization of cellular

membrane

Linezolid

Inhibits bacterial protein

synthesis by binding to 50S
subunit.

Red man syndrome

Nephrotoxicity

Myopathy and CPK

elevation
Inactivated by
surfactant

Thrombocytopenia
Optic neuritis
High risk for
serotonin syndrome.

Apolipoprotein Functions
1. ApoLP to Functions:
A-I Activates lCAT (LCAT) (I look like non-cap L)
C-II Cofactor for lipoprotein lipase
E rEmnant uptake by Liver. Without these, liver cant clear remnants.
B Both main TG trasporter start with ApoLP B on their membrane:
- Chylomicron (secreted from intestine) have B48. Mediates chylomicron assembly
and secretion by intestine.
- VLDL (secreted from liver) have B100. Mediated LDL uptake by extrahepatic
tissue.
(The Intestine have to process food 1st in order to have material for Liver.)
The chains of processing is:
Chylomicron > Chylomicron remnant
VLDL > IDL > LDL
HDL
2. Both main transporters of Triglyceride (TG) to tissue (1 from Intestine
Chylomicron, and 1 from Liver VLDL) carry 3 ApoLP: B (B48/chylomicron, B100/
VLDL), C-II and E.
3. After they gave TG to tissue (C-II and LP Lipase role), they loss C-II, then
only B and E left on Chylomicron remnant and IDL.
4. After return the remnant to liver, they loss E, then only B left on LDL.
5. HDL role is to take Cholesterol back to liver: so it has A-I (to Activate LCAT to
make Cholesterol Ester), and E (to go back to liver afterward).

Result:
Chylomicron (B48,C-II,E) > Chylomicron remnant (B48,E)
VLDL (B100,C-II,E) > IDL (B100,E) > LDL (B100)
HDL (A-I,E)

DNA polymerases

Prokaryotic Polymerase
# All DNA polymerases [ I, II, III ] have proofreading activity to remove
mismatched nucleotides via 3'5' exonuclease activity.
# Only DNA polymerase I has 5'3' exonuclease activity to remove and
replace RNA primers.
# DNA polymerase III is responsible for DNA synthesis in the leading
and lagging strands
Eukaryotic polymerases:
: primase, but also adds a few DNA to the newly-made primer.
: repair.
: mitochondrial polymerase.
: lagging strand. Protein PCNA attaches to it with the help of RFC.
Proofreads.
: leading strand. Proofreads.

Colon cancers
HNPCC- associated colon
adenocarcinoma

Sporadic colon
adenocarcinoma

Age of occurrence

Younger than 50

Older than 50

Location

Predominately right sided

Predominately left
sided

Multiple cancers

Common: synchronous ( occur

simultaneously with primary
cancer ), metachronous ( occurs
after the resection of the
primary cancer )

Uncommon

Source

Common right sided

Adenomatous
polyp

Genetic bases

Mutation in DNA mismatch

repair

Adenoma
carcinoma
sequence

Medications associated with tachyphylaxis

Nitrates
Antihistamines
Decongestants, e.g. Phenylephrine

Hemoglobin Electrophoresis

HbA: contain Glutamic acid ( -ve ) at

position 6. As such, it migrate the fastest
toward the anode.
HbS: contains Val ( neutral ) at
position 6. As such, it migrate
slower than HbA toward the
anode.

HbC: contains Lysine ( +ve ) at position 6.

As such, it migrates the slowest to the
anode.

Cathode ( attracts cations )

Anode ( attracts
anions )

ANP

Kidney

Afferent arteriole
dilatation

Smooth
muscles of the
blood vessels

Adrenal gland

Decrease aldosterone

Vasodilation and
extravasation

Increased GFR

Increased urinary
excretion of Na and H2O

The receptor ANF-A

Syphilis

Tertiary:
Many years after infection

Primary:
Chancre

Secondary:
Desquamating rash
on palms and soles.
Condylomata lata

Latent: asymptomatic period

Early: within one year after
resolution of 2dry.
Late: after one year after
resolution of 2dry.

in untreated individuals.
1. Neurosyphilis:
Asymptomatic
Subacute meningioencephalitis
Tabes dorsalis
Others
2. CVS:
Ascending aortic aneurism
and resultant aortic
regurgitation.
3. Gumma:
Initially painless but when
ulcerate they become
painful.
Usually cutaneous but could
occur sub.Q, liver, bones,
and others.

Collagen, again!

Procollagen
Procollagen peptidases
Deficient in E-D

Tropocollagen
Aggregation

Collagen

Out side of
fibroblasts and
SMCs

Contact lens infection

A 30-year-old female using home-made saline solution for the
disinfection and tap water for storing her contact lenses . She noticed
redness of her eyes and deterioration of vision and visited an
ophthalmologist who diagnosed her with severe retinitis.
Culture of the water as well as vitreous fluid would most likely reveal
a. Naegleria
b. Pneumocystis
c. Acanthamoeba
d. chlamydia
e. staphylococcus

Osler nodes: Oslers nodes (painful, palpable, erythematous lesions most often
involving the pads of the fingers and toes). Caused by immune complexes (they want
you to know that for Step 2). Infectious endocarditis and Roth spots are also due to
immune complexes leading immune vasculitis.
Janeway lesions (nontender, macular lesions most commonly involving the palms and
soles). Janeway lesions occur more frequently in endocarditis caused by
Staphylococcus aureus. Janeway lesions are caused by septic emboli. Subcutaneous
abscesses are found on histologic examination.
Splinter hemorrhages aka fingernail hemorrhage: narrow, red to reddish-brown lines
of blood beneath the nails. They run in the direction of nail growth and are named
splinter hemorrhages because they look like a splinter beneath the fingernail. The
hemorrhages may be caused by tiny clots that damage the small capillaries under
the nails or by vessel damage from swelling of the blood vessels (vasculitis). The most
common cause for splinter hemorrhages is trauma to the nail.

The lesions in Figures

A-C were tender and
represent Oslers nodes,
while the lesion in
Figure D was nontender
and represents a
Janeway lesion.

Weber Test

Neurosensory:
Softer sound
Conductive:
Louder sound

In Weber's, both air conduction ( AC )

and bone conduction ( BC ) are utilized.
In this test, what we looking for is
lateralization ( the patient hear the
sound louder in one side or the other ).
1. If there is a neurosensory deafness in
one side, the sound is heard better in
the other side ( the test lateralizes
away from the affected side ).
2. It lateralizes TO the side of the
conductive deafness ( just close one ear
and say LA LA LA, you would hear it
better in the closed side ).
So, a louder sound in weber test could
either be a neurosensory loss in the
softer side, or conductive loss in the
louder side. The weber could not tell
them apart.
Bilateral hearing loss would not result in
lateralization. Which ever the case is, we
have to proceed to the next test.

Rinne test

This goes on the assumption that the amount of AC should be at least 2

times the amount of BC ( AC = 2 BC ). e.g. If the patient was hearing
the sound when the tuning fork is on the mastoid ( position 1 ) for 4 min,
then he should hear the sound when the fork directly next to the ear
( position 2 ) for additional 4 min.
In position 1: AC = 4 min
BC = 4 min
In position 2: AC = 4 min
BC = 0 min
Total AC = 8
AC = 2 BC
BC = 4
If the AC is less than 2BC, then their is air conduction problem ( i.e.
conductive hearing loss )
In neurosensory loss, the total duration of both AC and BC are equally
reduced, but AC still be 2BC. e.g. BC = 3 min, AC = 6 min ( 3+3 )

Chromosomal Translocations
Burkitt's Lymphoma : 8urkitt's Lymphoma = t(8:14). CMYC
Mantle cell lymphoma : mantle ce11 lymphoma = t(11:14). Cyclin D
Follicular lymphoma ( 18 letter ) = t(14:18). Bcl-2
Others:
CML: Ph. Chromosome = t(9:22). Abl
Acute promyelocytic leukemia = t(15:17)
ALL = (12:21). Associated with good prognosis

Seizure

Generalized

Partial
Carbamezapine

Absence
Euthoaximde
Valproic

Myclonic
Tonic-Clonic
Phenytoin
Carba.
Valproic

Valporic

Role of Calcium in contraction

T-Tubule
1. Skeletal muscle:
Depolarization of the T-Tubule activates
the L type Ca channel. This, in turn, will
directly, via physical interaction, leads to L-type Ca
opening of RyR1 gate on the sarcoplasmic channel
reticulum and release of Ca. This Ca then
RyR1
interact with troponin and contraction
Dantrolene
happen. Skeletal muscles DO NOT depend on extracellular Ca. As such, its not
affected by Ca channels blockers.
2. Cardiac muscle:
In this muscle, L-type channel-RyR1 mechanical
coupling does not exist. Depolarization will cause
Ca channels on plasma membrane to open and Ca
influx occur. This Ca is bind and activates
sarcoplasmic RyR1 channel releasing the stored Ca
which gets into cytoplasm ( Ca induced Ca release
). The released Ca then binds to troponin and
contraction happens.

Ca

Ca

Cardiac muscle depends on extracellular Ca. As such, its affected by Ca

channel blockers.
3. Smooth muscles:
Similar to cardiac muscle in every aspect except when the sarcoplasmic Ca
is released, it binds to calmodulin to initiate contraction ( there is no
troponin in smooth muscle ).
Smooth muscles depends on extracellular Ca. Ca channel blockers affects.

Alcohol and pancreatitis

Alcohol

Vicious pancreatic
secretion ( alcohol
induces high protein
content )

Direct cellular toxicity

Spasm of
sphincter of
Oddi

Hemicholinium
Choline

Choline
AcCoA
Bromoacetylcholine
Acetylcholine

Ca

Ca

Choline

Acetate

Acetylcholine
esterase inhibitors

Botolinium

Atropine

Scala vestibuli

Oval window

Stapes

Round window

Scala tympani
Basilar membrane

High frequency sounds are best

detected by cochlea near the
base ( oval and round windows ).

Low frequency sounds are best

detected by cochlea near the
apex ( helicotrema ).

Helicotrema

Acute Hepatitis

1%
Fulminant hepatitis

95%
Complete resolution

50-80%
Stable chronic hepatitis

4-5%
Chronic hepatitis

20-50%
Cirrhosis

10%
HCC

Blotting Technique

Substance detected
Northern

RNA

Southern

DNA

Western

Protein

Southwestern

DNA-binding protein

Type of probe
Single stranded DNA or
RNA ( hyberidization )
Antibody
Double stranded DNA

Renal Calculi
Ca oxalate or
Ca phosphate

70-80%

Radioopaque

Struvite ( Mg
ammonium
sulphate or
triple
phosphate )

15%

Radioopaque

Colorless octahedron ( squire

crossed by diagonal line in
These patients tend to have hypercalciuria because the
2D view )
absorb too much Ca in the gut.
Rectangular prism ( coffin led
shape )

Associated with infection caused by Proteus Spp.

Acidic environment prevent their formation.

Uric acid

5%

Radiolucent

Yellow or red-brown diamond

or rhombus

Cystine

1%

Radioopaque

Flat, yellow, hexagonal

Acidic environment promote their formation.

See next page for images ...

Ca oxalate or
Ca phosphate

Colorless octahedron ( squire

crossed by diagonal line in
2D view )

Struvite ( Mg
ammonium
sulphate or
triple
phosphate

Rectangular prism ( coffin led

shape )

Uric acid

Yellow or red-brown diamond

or rhombus or star-shaped.

Cystine

Flat, yellow, hexagonal

When there is an abundance of stored energy in the form of

adipose tissue, the resultant high levels of leptin cross the bloodbrain barrier, binding to leptin receptors. Leptin receptor signaling
has two effects: it inhibits anabolic circuits that normally promote
food intake and inhibit energy expenditure, and, through a distinct
set of neurons, leptin triggers catabolic circuits. The net effect of
leptin, therefore, is to reduce food intake and promote energy
expenditure.

Decreased Fat cell mass

Decreased Leptin/insulin ration

Neuropeptide Y
Neurons

POMC
Neurons

Increased food intake

Wight gain

Increased Fat cell mass

Increased Leptin/insulin ratio

Neuropeptide Y
Neurons

POMC
Neurons

Decreased food intake

Wight loss

Congenital QT prolongation

There are two congenital syndromes that cause QT prolongation:

1. Jervell and Lange Nielsen: AR, associated with neurosensory deafness
2. Romano-Ward syndrome: more common, AD, no deafness.
Both predispose to torsades in young age.

Metabolic acidosis

Bicarb loss

When bicarb is lost, the kidney

tries to maintain electroneutrality
by increasing Cl reabsorption
from loop and distal tubule. This
would lead to state of
hypercholerima; hence the name
hyperchloremic metabolic acidosis.
Since a negative ion is lost and
another negative ion is gained,
anion gap stays normal.

Causes of bicarb loss ( i.e. causes of

normal anion gap MA ) are:
1. Diarrhea ( duodenum )
2. RTA: peeing out bicarb
3. Patient may be given Cl and forced
to loose bicarb [ for more causes, see
the mnemonic HARD ASS ].
Obviously, the latter two are
rare, so, anytime we have met.
acidosis with normal AG, the
diagnosis is D.

Gaining of new H (e.g.

ketones, aspirin )
The body buffers the new gained
H by consuming bicarb leading,
eventually, to state of low bicarb (
MA ). Since no Cl is retained
[ because no bicarb is lost from
the body and the electroneutrality
is maintained ], anion gap will be
increased.
Causes of increased anion gap
MA:
MULEPAK,
M: methanol> formic acid
( blindness ) and increase
osmolarity
U: uremia
L: lactic acidosis, the most
common.
E: ethanol, ethylene glycol
P: paraldehyde ( a drug that is no
used anymore ). The other drug is
INH
A: aspirin
K: ketoacidosis

Acetoacetyl-CoA
HMG-CoA reductase

Fibrates

7-alpha hydroxylase

Estrogen

Cholesterol

Bile acids

Bile

Gall bladder

Estrogen induces HMG-CoA

reductase to produces more
cholesterol. Some cholesterol is
used to produce bile acids via
the enzyme 7-alpha
hydroxylase. These bile acids
are used to solublize cholesterol
within the bile. Since fibrates
inhibits the enzyme 7-alpha
hydroxylase, they precipitate
cholesterol stones formation,
esp. in obese ladies, in whom,
cholesterol production is
increased because estrogen
induces cholesterol synthesis.

Gibbs free energy describes the both the direction in which a chemical
reaction will tend to proceed and and the concentration of reactants and
products that will be present at equilibrium. It can be calculated by the
following equation:

Deta G = - RTInK

Eq

If delta G un a negative number, Keq will be greater than 1 and the

concentration of the products will exceed that of the substrate. And if
delta G is a negative number, Keq will be lesser than 1 and the
concentration of the substrate will exceed that of the products.
Deta G of 0 will give us Keq of 1.

Retroperitoneal organs
Vessels: aorta, IVC and their branches
Solid organs: pancreas except the tail, kidneys and suprarenals
Holo organs: part 2,3 of the duodenum and part of part 4, the
ascending and descending colon, rectum, ureters and bladder.
Vertebral column and pelvic organs

NPH
Neither paroxysmal nor nocturnal

PIG-A gene [ defective in NPH ]

GPI protein
This proteins anchors CD55 and CD59 proteins to
RBCs surfaces. These CD proteins inactivate complex
preventing hemolysis and thrombosis.

Normal

NPH

Chromosomal Instability Disorders

XP
Ataxia Telangectasia
Fanconi Syndrome
Blooms Syndrome
Wischot Aldrich

Empysema
Tobacco stuff

Proteinase 3
Cathepsin G
Elastase
Matrix metaloprotinase

Proteases

Antioxidants
Free radicals that inhibit
antiprotease activity of alpha 1
antitrypsin.
Oxidants

Samter's Triad
Asthma, aspirin hypersensitivity and nasal polyposis. Occurs in
10% of patients with asthma treated with aspirin. The polyps
develop due to high concentrations of leukotrienes that results
from the fact that aspirin inhibits COXs pathways shunting all
arachidonic acid products to lipooxigenase pathway.

TTP: Adults

HUS: pediatrics

Renal failure

Fever Thrombocytopenia MAHA

CNS manifestations

MAHA: microangiopathic hemolytic anemia.

Note: unlike DIC, coagulation system is not activated in HUS-TTP.
As such, PT and PTT stay normal.

Glycogen breakdown control

Glucagon ( liver )

Epinephrine ( muscle )

Increased cAMP

Glycogen break
down.

Cognitive disorders

2
Coefficient of determination = ( the correlation Coefficient )

Likelihood ratio =

Sensitivity
1specificity

Types Of Studies

Descriptive Studies
Individual level
Case report
Case series
Cross-Sectional
Population level
Correlational ( ecologic )

Analytic Studies
Observational Studies
Case-Control
Cohort
Interventional
Randomized clinical trial

Ubiquitin
Mallory bodies, Lewy bodies, and neurofib tangles are all examples of
ubiquintation.

Biochemistry of fatty changes in alcohol

All problems arise from the high NADH/NAD ratio:
NADH
NADH
Acetate
Acetaldehyde
EOH
Malik enzyme

Oxaloacetate

Malate

NAD

Pyruvate

NADPH

G-3-P

DHAP
NADH

FAs synthesis
TG backbone

NAD

Hypoglycemia and acidosis:

Lactate

Pyruvate
NADH

Lactic acidosis

NAD

No pyruvate is available for gluconeogensis leading

to hypoglycemia.
Hydroxybutyric acid

Acetoacetate
NADH

NAD

Alcohol also inhibits VLDL assembly and release.

Acidosis

Homocysteinuria
Def: excess homocysteine in urine. Caused by three genetic defects ( lucus
heterogeneity ):
1. Cystathionine synthase deficiency
2. Decreased affinity for cystathionine for B6
3. Homocysteine methyltransferase deficiency
Homocysteine

Methionine

methyltransferase

B12/folate

Cystathionine
synthase

Homocysteine

B6

Cystathionine

Cysteine

Treatment according to the cause:

1. In Cystathionine synthase deficiency, all of the homocysteine will be
shunted toward methionine, as such, a lot of methionine will be formed and
B12 and folate will be consumed. No cysteine is formed. So treatment
consists of:
I. Decreasing methionine intake
II. Increasing B12 and folate intake
III. Supplying cysteine
2. Decreased affinity for cystathionine for B6:
Treated by giving maga doses of B6.
3. Homocysteine methyltransferase deficiency:
Nothing to be done except supplying cysteine.

Cluster Designations
CD
CD1: histiocytes
CD3: all T cell
CD4: Helper T cells
CD8: Cytotoxic T cells
CD10: this is the marker for most common leukemia in children; B
cell leukemia. It known as CALLA and that is common ALL antigen.
CD15, 30: RS cell
CD21: B lymphocytes
CD45: every WBC

Osmolarity Vs Osmolality
Both of them is defined as the concentration of osmotically active
particle in a solution. The difference is this:
In Osmolarity, this concentration is expressed in terms of osmoles
of solute per kg of the solvent.
While in Osmolality, this concentration is expressed in terms of
osmoles of solute per litter of the solution.
Osmole: the amount of substance that dissociate to form one
mole of osmotically active particle. E.g. One mole of glucose =
one osmole because its not ionizable. But one mole of NaCl = 2
osmoles because it dissociate into Na and Cl, all of which is
osmotically active.
Anyhow, Dr. Goljan says that the difference between these two is
garbage!

Five Causes of Hypoxemia

PAO2

PaO2

( P. Atm - H2O vapor

pressure )* 0.21 PCO2/0.8 = 150 MMHg

Cellular O2

Measured by ABG

Low O2 here = hypoxemia

Low O2 here =
hypoxia

1. High altitude:
# In high altitudes, P. Atm drops while other parameters, e.g. fiO2, stays the
same, i.e. 0.21.
# This will lead to low PAO2 and subsequently low PaO2.
# As such, no A-a gradient
# When the patients is given high conc. O2, e.g. 100%, his/her PaO2 rises.
# In these high altitudes, hypoxemia leads to hyperventilation which clear
more PCO2, giving more room for O2. Remember, in the equation, PCO2 is
subtracted.
Hyperventilation will lead to resp. alkalosis which is corrected after days by
the renal system via bicarb excretion. And by the way, this is the only acid
base disturbance in which the body is able to fully compensate for it.

2. Hypoventilation:
( P. Atm - H2O vapor pressure )* 0.21 - PCO2/0.8 = 150 MMHg
# The major consequence of hypoventilation is increased PCO2
in the alveoli which forces alveolar O2 to go down as will. This
will result in low PaO2, i.e. hypoxemia.
# This means there is no increase in A-a gradient ( see the
equation for A-a gradient below:

( P. Atm - H2O vapor pressure )* 0.21 - PCO2/0.8

- PaO2
a

# Hypoventilation is seen in patients on narcotics

# It responds to supplemental O2 very well.

= 16

3. Diffusion
# Gas diffusion from alveoli to capillary is impaired.
# This could either be caused by interstitial deposits that prevents
O2 from diffusing, or because RBCs has been speed up so no enough
time for O2 to get to them as might occur in exercise.
# This would lead to increased A-a gradient.
# It does respond to supplemental O2.

4. Shunting

Normally, the blood retaining to the heart

is 70% saturated. It enters the lung and
get out 95% saturated.
In shunt situation, certain % is bypassed
the lung ( 50% in the example ) and get
out with that 70% saturation.
When these two percentage combine in the
pulmonary vein, the resultant percent will
be the mean of them, i.e. the mean of 95%
and 70% = 82.5. Of note, this calculation is
applicable only if the shunted % is 50%.
Lower % have lesser effects.
# This will results in increased A-a
# And this form of hypoxemia does not
responds to O2 supplementation because
shunt % does not get O2 what so ever. If
the saturation of blood passing through the
lung is raised to 100%, this will results in
new combined sat of 85%. So no big
increase.

Alveoli
Pulmonary
artery

50% 95% sat. Pul. Vein

50%

70% sat

The 50% represents the % of blood

that goes either through the shunt or
the ventilated capillaries. Here we
have chosen 50% just for illustration
purpose. The bottom 50% would not
go through the alveoli to get O2, i.e.
forming shunt.

Examples of shunts:
Revered ASD, VSD, PDA
ARDS ( many alveoli are taken out
by the fluid in them ) and
pulmonary edema ( same as ARDS )

Area of high V/Q ratio. It receives

lesser amount of blood ( in this
example is 20% of blood entering the
lung ), and almost all of the RBCs get
their O2.

5. V/Q mismatch

20%

98%

P.E

89%

70%
80%

Area of high V/Q because

the clot preventing blood
from reaching the alveoli.
The blood will redistribute
to other areas ( e.g. The
green shaded area )
resulting in low V/Q ratio.

80%

This is an area of low V/Q ratio due

to higher % of blood goes through it.
This will results in lesser O2
saturation.
At the pulmonary vein, the combined
saturation will definitely be below the normal
(95%). In this example it will be the mean of
98%+80% which is 89%. When the patient is
supplemented with O2, his/her combined O2
will rise.

# V/Q mismatch is the MCC of hypoxemia because the causes for this are so
common: pneumonia, pulmonary embolism ( see the PE diagram above ), COPD.
# There is increased A-a gradient
# It respond to O2

Five causes of hypoxemia

Time to tell them apart!

A-a gradient
High A-a gradient

Normal A-a gradient

PaCO2

High

Hypoventilation

Responds to supplemented O2

Low

High
altitudes

Yes

V/Q mismatch
Diffusion limited

Clinically differentiated

No

Right to
left shunt

# Hyperkeratosis: increased thickness of stratum

corneum.
# Parakeratosis: hyperkeratosis with retention of nuclei
in stratum corneum.

In SSSS, the attachment

b/w keratinocytes in this
layer is lost.

# Acantholysis: separation of epidermal layers, with

the separation usually occurs at the level of stratum
spinosum.
# Acanthosis: epidermal hyperplasia ( increased
thickness of the stratum spinosum.

Recticulocytes filaments Vs basophilic stippling

Using special Gimmsa stain, reticulocytes will show RNA filaments. This
should not be confused with basophilic stippling, which represents
ribosomes and look like dot.
Note: basophilic stippling does not require special giemsa stain. Its
pathophysiology is explained below:
Lead denatures ribonuclease, and the purpose of ribonuclease is to break
down ribos; so if it get denatured ribosomes will persist.
Howell Jolly body is a peace of the nucleus in the RBCs in patients without
spleen.
Heinz bodies represents precipitated Hb as a result of oxidative
stress as in G6PD deficiency.

Spinal Cord Cross Section

Legs

Arms

Legs

Descending

ArmsAscending

For normocytic anemia, you need to look at the reticulocyte

count. First, you have to correct for the degree of anemia (Hct/
45 X ret ct). Then look to see if there is polychromasia, if there
is polychromasia (then divide by 2); 3% or higher = BM
responding normally, and 2% or lower = not responding

Eosinophilia
Note:
Protozoa, e.g. Malaria parasite, do not induce eosinophilia. Only
INVASIVE helminthes do.

What 2 tissues are resistant to invasion by cancer cells?

Cartilage and elastic tissue.

Cytotropoblast
Synctiotropoblsat
Wharton jelly
Blood sinusoid

Blood vessel
O2

Layers of the umbilical cord that O2 should cross

Umbilical vein has the highest O2 content,
Umbilical artery has the lowest O2 content,

Anatomy of the Juxtaglomerular Apparatus

Distal straight tubule

Extraglumerular mesangial cell

Macula densa,
detects low Na.

Afferent arteriole

Juxtaglomerular cells [ AKA

granular cell ], detects low
BP.

Metabolic Acidosis
All in here!
Metabolic acidosis is caused by low CHO3. CHO3 because low via one of
two ways:

1. Gain of H+ ions
Increased anion gap

2. Loss of HCO3Normal anion gap

For the list of causes,

see MUD PILES
1. We either poop it out, i.e. D
2. Pee it out: RTA type II ( proximal RTA ).
In these two cases, the kidney retains Cl to maintain
the electroneutrality, producing normal anion gap.
3. Forced to loose HCO3, i.e. saline infusion which
causes hyperchloremia, which causes bicarb loss to
maintain electroneutrality.
Anyway, causes of normal anion gap MA could be
memorized using HARD ASS mnemonic, in which, the
only clinically relevant are the D ( diarrhea ) and the
R ( RTA ). These two could be differentiated using
urine anion gap.
See the next page for detailed pathophysiology of
some of HARD ASS ...

Causes of normal anion gap metabolic acidosis

HARD ASS
H: Hyperalmentation
A: Addison's: No aldo. > decreased H excretion > HCl formation ( i.e. Cl
retained ).
R: RTA
Type I ( distal ): in ability to excrete acid in the distal tubules. This will
results in accumulation of acid in the body. The urine PH rises, leading
to renal stone formation.
Type II ( proximal ): inability to reabsorb bicarbs in the PCT. Urine PH
will not be low, so, no renal stones. Low serum bicarb induces calcium
resorption from bones leading to osteomalacia/rickets.
Type IV: decreased aldosterone production or effect ( similar to
addison's )
D: patient poops out bicarbs, with secondary retain of Cl that maintains
electroneutrality.
A: acetazolamide, just like RTA type II.
S: Spironolactone, like in addisons and RTA type IV.
S: saline infusion. Causes hyperchloremia, that forces the body to loose
bicarb to maintain electroneutrality and producing acidosis as a side
effect.

Urine Anion Gap ( UAG )

# Used to differentiate between diarrhea and RTA, the most clinically
relevant among the causes of normal anion gap metabolic acidosis.
# UAG = urine Na Cl.
# Acid excreted from the kidney, goes out as chloride. So, if the kidney
is able to excrete acid, then urine chloride goes up, generating negative
UAG. But when its unable to excrete acid, i.e. RTA, then urinary Cl drop,
generating positive UAG.
Bottom line is:
Negative UAG = kidney works
= diarrhea
Positive UAG = kidney did not work = RTA.

Metabolic alkalosis
Saline resistant
Saline sensitive
Urine Cl > 20 Eq/L
Urine Cl < 10 Eq/L
Causes:
Causes:
1. Vomiting
2. Diuretics

1. Hyperaldosteronism
2. Patter syndrome

Pathophysiology:

Pathophysiology:

Vomiting leads to loss of fluids and HCl

( which explains why urine Cl is low in
this category ).
Normally, pancreatic secretion, which is
rich is bicarb, is stimulated by acid in
the small intestine. As such, when H is
lost during vomiting, there would be
less of an stimulation for the pancreas
and it retains the bicarbs. So, up to
now, we have two causes for this
metabolic alkalosis: H loss and bicarb
retention.
Also, the fluid loss ( due to vomiting,
diuretics or any other cause ) will lead
to renal hypo-perfusion with
subsequent activation of RAA system.
Aldosterone is the important one here
because it causes more H loss and
generation of new bicarb, worsening
the alkalosis. There would also be
hypokalemia.

High aldo. ( as in Conn's ) leads to

hypernatremia, hypokalemia and major loss of
H ions, i.e. alkalosis.
Also, for every H lost, a new HCO3 will be
gained, contributing to alkalosis.
The resultant volume expansion will activate
ANP will force the kidney to loose a lot of Na
at the PCT level. A long this lost Na, there
would be Cl loss, hence, high Cl in urine.

In partter's, the famous Na/K/2Cl

cotransporter is not working ( as if the
patient is on continuos loop diuretic )
causing the body to loose a lot of fluid
leading to a state of hyper aldosteronemia,
with same pathophysiology as the above
results.

Rx:
Saline resistant: treatment of the
cause, e.g. Surgical resection of the
This would be called hypokalemic,
tumor.
hypochloremic metabolic alkalosis.
Volume contraction contribute much to the Saline sensitive:
Normal saline + potassium.
pathophys.

Hypersensitivity Pneumonitidis
Hypersensitivity pneumonitis (farmers lung, silofillers dz, bysinosis)
These are restrictive lung dzs.
Dont confuse farmers lung and silofillers dz they are BOTH seen in farmers.
So, remember one, the other is the other!
Silofillers dz put things in silos, which is a closed space, and fermentation of
gas occurs, the gas is nitrogen dioxide
Example: farmer went into a room in his barn and suddenly developed
wheezing and dyspnea, why? B/c he took in nitrogen dioxide, which is a
fermenting problem. (silo can explode b/c gas from fermentation).
Farmers lung thermophilic actinomyces (a mold).
Example: on tractor, dust being blown up in the air and thermophilic
actinomyces(which is a mold) is inhaled; leading to hypersensitivity and HPY
pneumonitis and they end up with a restrictive lung dz.
Bysinosis worker in textile industry(Lenin,cotton ,hemp), and they get
dyspnea.
Workers feel better over the weekend (no exposure to antigens), depression
occurs when returning to work on Monday .
These are the HPY and restrictive lung dzs.

Eosinophilia
Eosinophilia is the state of having high eosinophil granulocytes in the blood.
Normal ranges are between 0 and 0.5 109 per litre of blood. Eosinophilia is
presence of more than 450 cells/microL in blood.
The release of interleukin-5 by T cells, mast cells and macrophages
stimulates the production of eosinophils.
Diseases that feature eosinophilia: They can be easily be remembered by
the famous mnemonic "CHINA".
C - Connective tissue diseases
H - Helminthic (ie, worm) infections
I - Idiopathic HES
N - Neoplasia
A - Allergies
Connective tissue disease
# Eosinophilia-myalgia syndrome (due to tryptophan in the United States
in 1989)
# Rheumatoid arthritis
# Toxic-oil syndrome (due to contaminated rapeseed oil in Spain in 1981)
# Churg-Strauss vasculitis
# Coccidioidomycosis fungal infection
# Eosinophilic fasciitis

Parasitic infestations
# Ascariasis
# Schistosomiasis
# Trichinosis
# Strongyloidiasis
# Visceral larva migrans
# Gnathostomiasis
# Fascioliasis
# Paragonimiasis
Idiopathic hypereosinophilic syndrome
Neoplasia
# Lymphoma (e.g. Hodgkin lymphoma, non-Hodgkin lymphoma)
# Adult T-cell leukemia/lymphoma (ATLL)
# Human T-cell lymphotropic virus I (HTLV-I)
# Gastric or lung carcinoma (i.e. paraneoplastic eosinophilia)
# Eosinophilic leukemia (very rare)
Allergic
# Asthma
# Allergic rhinitis

Primary Immune Deficiences

1. B-cell: A, B, C
A: selective Ig A Deficiency
B: B ruton's
C: C ommon variable immunodeficiency
2. T-cell: TICH
T: Thymic aplasia
I: IL-12 deficiency
C: chronic mucocutanous candidiasis
H: hyper-IgE syndrome ( Job's ). Don't confuse it with hyper IgM
syndrome.
3. Combined B and T cell deficiencies:
SCID
Ataxia Telangectasia
Hyper-IgM syndrome
Wiskott-Aldrich

Thymic aplasia and SCID

have absent thymic shadow.
Thymic aplasia has the
feature of CATCH-22 that
set it apart.

Phagocytic dysfunctions:
Leukocyte adhesion deficiency
Chediac hegashi
CGD

WBC are X-linked

W: wiskott
B: brutons
C: CGD

Antibody diversity is generated by:

Random "recombination" of VJ (light-chain) or V (D)J (heavy-chain) genes
Random combination of heavy chains with light chains
Somatic hypermutation (following antigen stimulation)
Addition of nucleotides to DNA during recombination (see lst entry in this
list) by terminal deoxynucleotidyl transferase.

Haldane Vs Bohr effect

CO2

Cl HCO3

Cl
CO2 + H2O

CA

HCO3 + H
H+ + Hb-

HHb
O2

In the lungs, the high conc. of O2 will force the HHb form of Hb to
release its proton, forming a relaxed form of Hb. This proton is
combined with HCO3 to form CO2 and H2O ( via carbonic unhydrase,
CA ). When the reaction goes in this direction, i.e. the red direction,
the effect is called Haldane effect.
In tissues, the high conc. of CO2 will force the reaction to go into
the direction of the black hemi-arrows, an effect known as Bohr
effect.

Statistics
1. Relative risk ( RR ): incidence exposed/incidence non exposed.
2. Relative risk reduction ( RRR ): 1 RR
3. Absolute risk reduction/increase: this is AKA attributable risk.
When we speak about interventional study, the attributable risk will be calculated
as absolute risk reduction ( because the intervention we are doing is supposed to
reduce the absolute risk ), which equal to: incidence of cases incidence of control.
If we speak about exposure Vs non-exposure, then the attributable risk will be
calculated as absolute risk increase, which equals to incidence of exposed
incidence of non-exposed.
E.g. In studying the effect of smocking on lung cancer, the incidence of lung cancer
in smokers is 6/10 and in non smackers is 4/10. The ARR, which is the attributable
risk = 6/10 - 4-10= 2/10, i.e. the smacking has the increased the risk of lung
cancer by 2/10 from the base line of 4/10 to become 6/10.
4. ARP is the attributable risk percent that represents the excess risk in the
exposed population that can be attribute to the risk factor. It = ( Risk in exposed Risk in unexposed)/ Risk in exposed. Also it can be calculated as follows: ARP =
(RR-1)/RR.
5. NNT = 1/ ARR. Absolute risk reduction ( ARR ) is the same good old attributable
risk! Just here we calculate it as 'incidence of non-treated ( control ) incidence of
treated ( experimental group )'.
Obviously, ARR and NNT are calculated in clinical trials.
6.NNH = 1/ ARI. Relative risk increase ( ARI ) is the same good old attributable risk!
Just here we calculate it as 'incidence of exposed ( cases ) incidence of non
exposed ( control )'.

Hirsutism

Caused by an excess of either of two hormones:

Testosterone, which is mainly

form the ovary.

DHA sulphate, which is an

androgen that comes from
adrenal gland.

# Hirsutism = increased hair in normal hair bearing areas

# Virilization = hirstuism, plus male secondary sexual characteristics (zits,
acne, deeper voice), clitoromegaly (pathognomonic)

Visual field defects: craniopharyngioma Vs Pituitary adenoma

Pituitary adenoma begin as a bitemporal superior quadrantopia while a

craniopharyngioma begin as a bitemporal inferior quadrantopia.
Pitutary hormone are lost in the following order:
1. Gonadotrphic hormones: leading to amenorrhea or impotence
2. Growth hormone: Pituitary Dwarfism, fasting hypoglycemia
3. TSH
Note:
4. ACTH: fatigue, hypoglycemia
Sleep is the strongest stimulant for GH.
5. Prolactin
Arginine and histidine are the next best
stimulant ( body builders use these ).
Action of growth hormones

Increase AA absorption
Involved in gluconeogensis

Act of the liver to increase the

secretion of ILGF

Insulin-like growth factor ( AKA

somatomedin )
Increase bone and tissue growth

Trisomy 16 is the most common form of trisomy. Its incompatible with

life ( 1st trimester demise ). Starting from the 2nd trimester, the most
common trisomy is trisomy 21.

Fibrates and cholesterol gall stones

HMG-CoA reductase

Cholesterol
( insoluble )

7-alpha hydroxylase

Fibrates

Bile acids
( soluble )

Fibrates increase the activity of the enzyme HMG-CoA reductase ( increasing

cholestrol synthesis ) and inhibit the enzyme 7-alpha hydroxylase ( decreasing
cholesterol solublization ). These two effects lead to increased tendency to form
cholesterol stone in patients on fibrates.

Fibrates mechanism of action:

1. The are PPAR agonist that lead to increased synthesis of lipoprotein lipase,
causing a significant reduction in triglycerides (TGs ) level.
2. They increase theexpression of enzymes involved in fatty acids break down,
which results in a decreased availability of TGs for VLDL synthesis.
3. They increase level of Apo-AI and Apo-AII, both of which promote increased
HDL level.

Note: inhibition of 7-alpha hydroxylase will lead to accumulation of

cholesterol within the liver thus down regulating LDL receptor in the liver
with resultant hypercholesterolemia.

Porphyrias
Succinyl-CoA
Glycine
Aminolaevulinic acid

Porphobilinogen
Acute intermittent
porphyria

Porphobilinogen deaminase ( PBGD )

AKA Hydroxymethylbilane Synthetase

Hydroxymethylbilane

Uroporphyrinogen
Uroporphyrinogen
decarboxylase

Porphyria cutanea tarda

Coproporphyrinogen

There are about 7 different types of

porphyria, only TWO are important
for USMLE step 1.

Heme

Porphyria

Beez!
B1

Thiamine

B2

Riboflavin

B3

Niacin

B4

Lipoic acid

B5

Pantothenic acid

B6

Pyridoxine

B7

Biotin

B9

Folic acid

B12

Cyanocobalamin

DNA and RNA polymerases

Eukaryotes Vs prokaryotes
DNA polymerases
Eukaryotes

primers . Proofreads.
: leading strand. Proofreads.

Prokaryotes
Pol I: removes RNA primer and replace
it with DNA.
Pol II: repair functions, SOS repair.
Pol III: the main enzyme for
polymerization because it works really
fast and have proof-reading capability.
It synthesizes both leading and lagging
strands
Pol IV, V: repair functions, SOS repair.

RNA polymerases
RNA Pol I: rRNA
RNA Pol II: mRNA
RNA Pol III: tRNA, snRNA

Prokaryotes RNA polymerase is one

that has several subuints:
Alpha, beta, beta prime ( these three
are called corenzyme ) and sigma
factor ( when added, the whole thing
is called holoenzyme). BTW: Rifampin
blocks beta subunits.

Substitution mutation

Transition
Purine is replaced by another purine
or
Pyrimidine is replaced by another
Pyrimidine

Transversion
Purine is replaced by Pyrimidine
or
Pyrimidine is replaced by purine

Sensory nerves of the external ear

Posterior half of the external
ear canal:
Auricular branch of vagus nerve

Upper part of the auricle:

Lesser occipital nerve

Anterior half of the

external ear canal:
Auriculotemporal
nerve

Lower part of the auricle:

Greater auricular nerve
Lesser occipital nerve, The great auricular nerve : cervical plexus
Auriculotemporal nerve: mandibular nerve
And I have a feeling that the auricular branch of the vagus is from
the vagus.

Branches of Vagus to the Neck

SLN

PN

Vocal cords

RLN

Cricothyroid

Three nerves:
1. Pharyngeal Nerve supplies all of the muscles of pharynx and soft
palate EXCEPT stylopharyngeus, which receives its intervention from the
9th. The 9th also sensory innervates the pharyngeal mucosa.
2. Superior laryngeal nerve. This nerve has two branches:
I. Internal branch that is sensory and supplies the laryngeal mucosa
above the vocal cords [ piriform recess ]. The superior laryngeal artery
runs with this nerve - be careful during thyroid surgery. BTW: Sensory
innervation below the vocal cords is from the recurrent L. nerve.
II. External branch that supply the cricothyroid. The superior thyroid
artery runs with this nerve.
3. The recurrent nerve (under the aorta) supplies all the muscles of
larynx EXCEPT the cricothyroid and cricoretinoid that open glottis only
muscle behind trachea .