5-25-15

Pathology
o Inflammation apoptosis
Necrosis
Cell injury
Ischemia: susceptl areas
Infarcts: red vs pale
Shock
Atrophy
Inflammation
Leukocyte extravasation
Free radical injury
Wound healing
Granulmoatus dx
Exudate vs transudate
ESR
Iron poisoing
Amyloidosis
On histological exam, a dying cell is noted to
lack signs of acute inflammation in its
vicinity. What type of cell death has likely
occurred?
o Apoptosis

 Western blot is used to study this killer T cell

efector molc that degrades DNA and is
involved in extrinsic pathway?
o Granzyme
What immune cells utilize perforns and
granzymes?
o Killer (cytotoxic) T cells
Changes in the proprotions of what 2 factors
lead to increasd mitochondria permeability
and conseuqnetly cytochrome c release?
o Bcl-2 or Bax
Pro-aptotic factor
Bax (pro-apoptoic factor
Anti-apoptoic factor?
Bcl-2
o An increase in Bax and/or a decrease in
Bcl-2?
Induces apoptosis
Nuclear shrinkage is due to?
o Pyknosis
Where as nuclear fragmentation is due to?
o Karyorrhexis
Pro-apoptoic gene?
o Bax
o Anti-apoptoci gene?
Bcl-2

 Western blot is used to study this killer T cell

effector molc that punchesw hols int eh
plasma membrane?
o Perforin
Under what conditions does intrinsic
apoptosis occur?
o Embryogenesis
Hormone induction (i.e.
mensturation)
Menopause
Atrophy
o (injurious stimuli)
Radiation
HYPOXIA
Toxins
Before the formation of apoptoci bodies,
what 4 proccess occur in a cell underoing
apoptosis?
o Cell shrinkage; pyknosis and basophilia,
membrane blebbing and karyorrhexis
What is the final common pathway of the
intrinsic and extrinsic pathway of apoptosis?
o Activation of cytosolic caspases
What are the 2 extrinsic apoptoic pathways?
o 1) ligand-receptor interactions

Fas ligand binding to Fas receptor

(CD95) (death receptor)
o 2) cytocic T cells release of granzyne B
and performins
Which pathway or pathways of apoptosis
requires ATP (intrainsic and/or extrinsic)
o Both intrinsic and extrinsic
APOPTOSIS (Dr. Gojan) always
require energy
What is apoptosis?
o Programmed cell death.
Give an example of how withdrawing a
growth factor can lead to apoptosis via the
intrinsic pathway?
o Withdrawal of IL-2 after an immune
response lead to apoptosis of
proliferating effector cells.
What type of necoris is a/w with TB?
o Caseous
USMLE:
o An alcoholic has sveral bouts of acute
pancreatiis. If he does not stop rinking,
watht yep of necrosis can you expect in
hs pancrease?
Fatty necoriss (saponification via
lipase)

They can ask peripancreatic fat

which is the fat necoriss
Which parenchymal will be
liquefactive according to
firecrackers
enzymatic degradation and protein
denaturalizing caused by exogenous cell
injury results itn eh relase of intracell
component?
o Necrosis
Liquefactive necoriss occurs most commonly
in what organ?
o Brain
What is the main difference between dry and
wet gangrene?
o Ischemic coagulation gangrene?
Dry gangrene
o Necrosis superimposed with a bacterial
infection?
Wet gangrene
o Ischemia happens with both of them the
same cause and when infection happens
you get wet
What type of necoriss limbs and GI tract?
o Gangrenous necrosis

 What morphologic type of necoriss MC

occurs in the blood vessels?
o Fibrinoid necoriss
Coagualtive necoris soccurs msotc ommonly
in what organ?
o Heart, liver and kidney
USMLE:
o 49 yo male has a sudden onset chest
pain diagnosed as MI. what type of
necoris would b eseen?
Cogaulative necoriss
Pervuian immigrant peresnts with a
productive cough. Culture stain acid fast. If
he is not rx, what type of necoris do you
expect
o Pt has TB
not treated he will develop
casious necoris (also seen with?
Systemic fungi
50 yo man with pneumonia develosp a
parapneumonic effusion. What type of
necoriss occurs in this effucsion?
o Liquifactive nencorsis
What ist he main dif between necoris asnd
apotposi?
o Necoris s a/w inflammation

 Regarding cell injury, is plasma membrane

damage reversible or irreversible?
o Irreversible
Regarding cell injury, are nuclear pyknosis,
karylosy and karyhexis reversible or
irreverabile?
o Irreversible
regardingClel injyr, is glycogen depletion?
o Reversible
Calcium influx that leads to capsse
activation R or I?
o Irrersible (caspse activation leads
aptosis, which is irreversible )
Lack of ATP leads ot cellular swelling.
o Reverislbe
w/o ATP, Na/K/ATPase pumps do
not work ledas to massive sliudm
and H2O influx. swelling
is fatty change R or I?
oR
Increased mitochondrial permaiblity R or I?
oI
Is lysoomsal rupture R or I?
oI
Ncuelar chromatic clumjkping R or I?
oR

 Ribosomal detachment R or I?
oR
USMLE
o Pts cell shows nuclear clumping and
fragmentation. Is this R or I signs of cell
injury?
Irreversible: pyknosis (nuclear
clumping) and karyolysis (nuclear
framgantion) are irrersbiel changes

What part of the kidney is most suscpeti to

hypoxia?
o Proximal tuble (cortex) and thick
ascending limb (medulla)
Because they are the watershed
areas.
Hypoxic ischemic ecneaplophaty primarily
affects which cells of the hippocampus?
o Pyramidal cells (purkinje cells are
affected as well)
Liver (most suscpetile to ischemia)
o Zone 3
Area around the central vein
USMLE
o A man with arterial stenosis often has
left upper quandra pain after eating a

large meal. What watershed area is most

likely affected?
Splenic flexure
Which parts of the brain are more suscpeti to
hypoxia?
o Bounadaires
Anteria, middle, posteiroe cerebral
artery
Watershed areas
What part of the hear tis most suscpet to
hyposxia?
o Subendocardial tissue
MOA?
Watershed area
An area that receives dual blood supply
fromt eh most distal branches of two
arteries?
o Watershed area
3 organs manifest irrerbisl eishema with a
pale infarction?
o Heart, spleen kidney
This colored infarct can occur after
reperfusion b/c it suggests hemorrhage
o Red infarct
Can los tissue with collateral circulation?
o Red

 Occur in soldi tusses with asingle blood

supply?
o Pale
3 organst manifest irrersibel ishcmeia with a
red infarction?
o Liver, lungs, intestines,
Why can reperfusion of an organ lead to
more dmanage?
o Injury is due to dmange ffree radicals
USMLE:
o A man with a gunshot wound is rushed to
the ER. HE is cold, clammy and has a low
BP and high TPR. What state is this?
Hypovolemic shock
Cardiaonci shock
o Low cardiac OUTput failure
Pt with sepetic shock can be warm to the
touch. Penhomnomen?
o Dilated arterials
TPR?
Low
In pts with septic shock, there is
o TPR?
Dfecreased
Hypovolemic shock?
o Cradiac output failure?

Low
Pt admitted to the ICU is cold and clammy.
o Hypovolemic or dardiogneic
In a pt with hypovolimc/cardiogenic shock,
TPR?
o Incrase
To componste for low CO
Pt expierences widespread bactermia. He is
warm to the touch. CO to be?
o High
Septic shock
Septic shock CO state?
o High
Reduction in the size or number of cells?
o Atreophy
Causes?
Decrase in hromones
Blood flow,
Innervation,
Nutrients
Occlusion of secretary ducts
Incrase in pressure
o A man severs his right bracial pleux can
cannot more his arm.
He develops vast mucsuclar atrophy,
unepxoed by lack of use alone.

MOA?
o Dnervation fo msucles in his
right arm accelerated the
atrophy
o Why does the endoemetrial ining of the
uterus undero atrophy after menopause?
It loses of growth signals from
endogenous hromeons
A man is diagnosed with CF. What sithe
pathogenesis of his pancreatic atrophy ove
rtthe long term?
o Occlusion fo secretary ducts
40 yo man has PF. Wha type cell type in his
lugns will repdomiante in cuasing the
pathologic hanges?
o Fibroblasts
50 yo man has left lower lobe exudative
inflammation from bacterial pneumonia.
What sepcts of the inflammatory process led
to this?
o Increased?
Vascular permability
o Vasodilation
o Endothelial injury
Abnormal ocmmuicatnion between 2
epitheliaized surfaces

o Fisutal
Present?
Resolution phase of
inflammation
What is the ce3lularl component of the
inflammatory process?
o Neutrophil extrvation (circulation to the
in injured tissue) to mediate?
Phagocytosis;
Degranulation
Inflammatory mediator release
What cells and proteins mediate acute
inflammation?
o Neutrophils, esoinphopls
o And antibodies
Chronic inflammation?
o Persistent destruction and repair
Charc of granulation tissue?
o Highly vascularized fibroti citssue
Present?
Resolution phse of inflammation
Inflammation:
o What should normally happen in the
resoluation phase of inflammation?
Restoration Normal tissue structure
What is an abscess?

o Fibrosis surrounding pus

When are abscess present?
Resolution phase of inflammation

USMLE:
o Chronic inflammation is mediabed by
cells?
Mononuclear cells
W
What are the pathological charc
of such an inflammation?
o Persistent destruction and
repair
Nodular collecitons of epithelioid
macorphages and giant cells?
o Granuloma
Chronic phase of inflammation
4 main cytokinase
o Triggered by bacterial prodcuts) that
guide leukocytes to a site of injury or
infection (CILK)
C5a
IL-8
LTB4
Kallikrein
Tight binding is mediated by?

o ICAM-1
On the vascular endotheium
o And by binding to what? Ont eh
leukyoctyes
LFA-1 (integrin)
4 steps involved in leukocyte extrvation:
o Rolling
o Tight binding
o Diapedesis
o Migration
Leucokcytes travel between endotehliuc
cells adne xits the blood vessel?
o Diapedesis
Mediated by ?
Ont eh vascular endothium?
o PECAM-1
And binding to on the leukocytes?
o PECAM-1
The cell travesl to the site of infection or
injury with tethe guidance of chemotactic
signals?
o Migration
Rolling is medicated by what ont eh vascular
endoium?
o E and P selectins
o By binding on the leukocytes

Sialyl Lewis
Name 3 pathays for free radical
degradation?
o Antioxidants
(vitamins, ACE)
o Enzymes (i.e.?
Catalase, superoxide dismutase)
o Spontaneous degradation (decay)
Free radical damage by carbon tetrachlrodi
causes what pathlogic change int eh uman
body?
o Fatty change in the liver
Some enzyems that degrade free radicals:
o Catalase
o Glutathione peroxidase
o Superoxide dismutase
Via what mechiansid do free radicals
damage cells?
o Membrane lipid peroxidation,
o Protein modification
o DNA breakage
3 vit with antioxidants properties that
involve in degrading free radicals?
o E, A, C
Fat soluble vitamins?
o DEAK

 USMLE:
o An infant is born at 22 weeks gestation.
Exposure to free radicals predispose him
towha tpathological processes in his
eyes and lung?
Bronchopulmonary dyslplaisa (lungs)
Retionphaty of prematurity (eyes )
Pt undergoes thrombolysis for acute limb
ischemia. What type of fre radical injury is
of most concern?
o Reperfusion injury
o MI pt that had fibrinolysis: why do
troponin rise again?
Free radiacl injury can be induced by expose
to what substances and processes?
o Radiation
o Heavy metals
o Metabolism of drugs (phase 1)
o Redox reactions
o NO
o Leukocyte oxidative burst
Wound healing
o Which phase of wound healing has
infiltration of paltelets, neutorphils and
macrophages at the site of injury?
Inflammatory phase!!!

o Has infiltration of fibroblasts,

myofibrblyasts, endotehlic cells, and
keratinocytes at the site of injury?
Proliferative phase
o Which cells are most important in
mediating the remodling process of
wound healing?
Fibroblasts
o In which phase of wound healing is type
III collagen replaed by type I collagen?
Remodeling phase
o MOA?
To increase tensile
strength of tissue .
What are the 3 phases of wound healing, in
order?

o Inflammation, proliferative, remodeling

Whend eos the prolifeative phase of wound
healing occur?
o 2 to 3 dyas

After wound
In which phase is the wound healing process
one week after an injury?
o Remodeling phase
What are the charc of the inflma phase?
o Clot formation
o Incrased vessel permability
o Neutrophil migrate into tissue
o Macoprhage clearance of debris two
days later
Which wound healing phase has collagen
deposition, angioegeniss, clot dissolution,
epitheliuc cell rplofieration and wound
contraction?
o Prlofieratif phase
When does the ifnlammaotyr phase of
wound healing occur?
o Immediatlye after injury
Granlumotase dixses
o Why must you check for granulmostu dx
before starting an anti-tumor necoriss
factor medication?
b/c these medication break down
granulomas and can predispose to
dissiminated disease

 Th1 cells secrete gamma-interfern activagin

macrophages, macropahgese secrete TNFalpha, inducing/maintain granulmona
formation?
o Granuloma forms
G dxs:
o TB
o Fungi (histoplasmosis)
o Syphilis (T. pallidum)
o M. leprae (leprosy)
o Cat scrath fever (B. henselae)
o Sarcoidosis
o Crohns
o berylliosisUSMLE
a Mexican immigrant not up to date
on vaccines presents wth liver
granulmoas secondary to a
productive cough. What cuased his
granuloma?
TB
o Does increased fluid pressure cause
formation of a transudate or exudate?
Transudate
Serous exudate
Transudate
Types[edit]

Purulent or suppurative exudate consists of plasma with both active and

dead neutrophils, fibrinogen, and necrotic parenchymal cells. This kind of exudate is consistent
with more severe infections, and is commonly referred to as pus.

Fibrinous exudate is composed mainly of fibrinogen and fibrin. It is characteristic of

rheumatic carditis, but is seen in all severe injuries such as strep throat and bacterial
pneumonia. Fibrinous inflammation is often difficult to resolve due to blood vessels growing into
the exudate and filling space that was occupied by fibrin. Often, large amounts of antibiotics are
necessary for resolution.

Catarrhal exudate is seen in the nose and throat and is characterized by a high content of
mucus.

Serous exudate (sometimes classified as serous transudate) is usually seen in mild

inflammation, with relatively low protein.[6] Its consistency resembles that of serum, and can
usually be seen in certain disease states like tuberculosis. (See below for difference between
transudate and exudate)

Malignant (or cancerous) pleural effusion is effusion where cancer cells are present.[7] It is
usually classified as exudate.

Exudates vs. transudates[edit]

Transudate vs. exudate

view

talk

edit

Transudate

Exudate

Increased hydrostatic
Main causes

pressure,
Decreased colloid

Inflammation-Increased Vascular Permeability

osmotic pressure
Appearance

Clear[8]

Cloudy[8]

Specific gravity

< 1.012

> 1.020

Protein content

< 2.5 g/dL

> 2.9 g/dL[9]

< 0.5

> 0.5[10]

fluid protein/

serum protein
Difference of
albumin content

> 1.2 g/dL

< 1.2 g/dL[11]

< 0.6 or < 23

> 0.6[9] or > 23[10]

< 45 mg/dL

> 45 mg/dL[9]

with blood albumin

fluid LDH
upper limit for serum
Cholesterol content

There is an important distinction between transudates and exudates. Transudates are caused by
disturbances ofhydrostatic or colloid osmotic pressure, not by inflammation. They have a low protein
content in comparison to exudates. Medical distinction between transudates and exudates is through
the measurement of the specific gravity of extracted fluid. Specific gravity is used to measure the
protein content of the fluid. The higher the specific gravity, the greater the likelihood
of capillary permeability changes in relation to body cavities. For example, the specific gravity of the
transudate is usually less than 1.012 and a protein content of less than 2 g/100 mL (2 g%). Rivalta
test may be used to differentiate an exudate from a transudate. It is not clear if there is a distinction
in the difference of transudates and exudates in plants.

Trausndate can occur in the setting of excess

sodium ?
o Retention
Transudate are protein poor compared to
exduates
o Sepcfici gravity < less than 1.012

Transudates are characted by few cells, little protein and specfici gravity?

< 1.012

Exudates many cells, much

protein, specfici gravity?
o > 1.020

USMLE:
o A pt with decompensated CHF has

a pelural effusion.l Is the fluid

more likely to be T or E?
Transudative
Increased hydrostatic
pressure
o A 40 yo man with bacterial
pneumonia has a pleural effusion
on chest xray.
Exudative
Damage to endothelium
2 pathologica processes that lead to
the formation fo exudates:
o Lympathic obsturciton and
inflammation
Transudate can result from

o Oncotic pressure in the

vasculature?
Decreased
ESR (erythrocyte sedimentation rate)
o Least 2 conditions that can
predispose pts to a lower ESR
Sickle cell anemia
Polycythemia
CHF
USMLE:
o A med student worries a pregnant
women has an b/c of her high ESR.
Do you agree?

No. ESR can naturally be increased

in pregnancy w/o superimposed
infection
Name at least 3 conditions that can cause an
elevated ESR
o Infection, inflammation, cancer,
pregnancy
o SLE
SOAP BRAIN MD
SEROSITIS
ORAL ULCERS

 ARTHRITIS
PHOTOSENSITIVTY
RAYNAUDS PHENOMENOM
Anti-histones
SHIPP
o Q-chimppps
Quinidine
Chlorpromazine
Hydralzine
Isoniazide
Methyldopa
Procainamide
Phenytoin
Penicylamine
Sulfonamides
What is the Mecnahims of cell death iron
poisoing?
o Membrane lipid peroxidation
In what population are your particularly
worried about iron poisoing?
o Children
o Why?
Iron poisoining is one of the MCC of
death in children secondary to
toxco.lgoci agents
What is the acute sign of iron poisoining?

o Gastric bleeding
What are the isgns of chronic iron poisoing?
o Metabolic acidosis scarring leading to
GI obstruction
USMLE:
o A man with no surgical history decides to
take 5 iron supplemnts a day. He later
develops a small bowle obstctruion?
MOA?
Chronic iron poisoing cause
scarring leads to the
gastrointestinal obstruction.
USMLE:
o A 5 yo is rushed to the ER after
swallowing 10 mutlivtamin pills. He has
acute gastric bleeding.
Likely cause?
Iron poisoing from the MVs
Amyloidosis
o Tissue affected by amyloidosis may
have?
Waxy appearance
o What protein is depsoisted in mayloidoss
in pts with medullary carcinoma of the
thyroid?
A-CAL

o What ist he precursor protein?

Derived rom calcitonin
Dialysis-asosicated amylidsoi is charac by
dpeostion of what protein?
o B2-microglobulin
What is the name of its precursor protein?
o Derived from Major histocopatiblity
complex class 1 protein (MHC1)
2ndary maylodiss is charc by the deposition
of AA rptoein. From what protein is AA
rpteoin derived?
o Serum amyloid-accoisted rptoein.
High serum levels chornic
inflammation USMLE
USMLE
o Pt suffers from RA. If her tisseus are
found to have amyloid deposition.
Expect?
Secondary amylodis
Pt suffers from horrible form of cardiac and
neurological amylodis.s wha mutation is
responbile
o The pt has ATTR neurlogic/carida
amylodiss, due to transthyretin (TTR or
prealmbumin) gene mutation

ATTR

transthyretin

ransthyretin is a protein that is mainly formed in the liver that transports

thyroxine and retinol binding protein.[4] A mutant form of a normal serum
protein that is deposited in the genetically determined familial amyloid
polyneuropathies. TTR is also deposited in the heart in senile systemic
amyloidosis.[11] Also found in leptomeningeal amyloidosis.

Pt suffers from a heritable form of cardiac

and neurlogica amyldoisis
o Gene mutation?
Primary amlydoiss is charac by the dpeosion
of AL protein.
o Form what priteoin is this AL derived
from?

Ig Light chain
Which type of amylidos is charc by AL
protein derived from Ig light chain?
o Bence jones amyloidosis
What dx can cause amyloidsi from an
cexcess of Ig light chain?
o Multiple myeloma
What is charc hisotlogica finding in tissed
affected by amlyodis?
o B pleated sheet that show apple green
birefreingche when stain with Congo red
and viewed under polarized light
Amyloidosis in AD pts is charac by
deposition of what protein?
o B-amyloid
What is the name of its precursor
protein?
Derived from ?
o Amyloid precursor protein
Senile cardiac amyloidosis sis characterized
by the depsitn of what protein?
o tr

o Transthyretin
What is the name of its repcurs
protein?
Derived from AF
AF Amyloidosis Amyloidosis Center | Boston University
www.bu.edu/amyloid/research/laboratory.../af-2/
o
o
Boston University

AF Amyloidosis. Studies on the familial forms of systemic amyloidosis are aimed at

understanding the pathogenetic mechanism by which normally soluble ...

o
Describe the pathophyskogy fo age related
(senile) systemic amlyodis)