Pathology

Front 1

after injury, tell me the pathway that leads to

cellular swelling

Back 1

depletion of ATP-->dec activity of energy pump (K/Na/ATP pump) -->inc Na influx-->(water follows Na)-->inc water influx

Front 2

after injury, tell me the pathway that leads to

chromatin clumping

Back 2

ATP depletion-->inc glycolysis -->lactic acid --> dec pH-->chromatin clumping

Front 3

after injury, tell me the pathway that leads to
lipid deposition

Back 3

ATP depletion-->detachment of ribosomes -->dec protein synthesis--> lipid deposition

Front 4

tell me all the effects of reversible injury
(don't look at the arrows)

Back 4

Front 5

fibroblasts, dermal epithelium are very/moderately/not sensitive to hypoxia

Back 5

not

Front 6

effects of irreversible damage

Back 6

Front 7

what does an early dead cell look like?

Back 7

Front 8

Back 8

mallory bodies

Front 9

what is this?

Back 9

lipid deposition in an alchoholic

Front 10

what is this?

Back 10

lipid deposition in an alcoholic

Front 11

another class of reversible changes (aside from mild hypoxia)--> intracellular accumulations

common in which 2 organs

Back 11

liver, heart

Front 12

fatty accumulation
can be large/small droplets

technical terms?

Back 12

macrosteatosis (large droplets)

microsteatosis (small droplets)

Front 13

why is the liver esp prone to fatty change

Back 13

cause it synthesizes lipoprotiens

so makes a lot of triglycerides-->any perturbation in lipoprotein assembly can result in fatty change

Front 14

causes of fatty change in liver?

Back 14

1) EtOH intake-->produces glycerophosphate which leads to inc esterification of fatty acids into tg's
2) untreated diabetes
(insulin controls lipolysis in adipocytes...no effective insulin-->escessive lipolysis-->too much FA's going to the liver)
3) decreased apolipoprotein synthesis (occurs in protein malnutrition, CCl4 and phosphorous poisoning...)

Front 15

what's the common features of the causes of fatty liver?

Back 15

either inc synthesis of lipids....or decreased packaging/export

Front 16

aside from fat, what are other chemical accumulations in cells?

Back 16

glycogen

nondegradable exogenous material (carbon pigment-->anthracosis)
iron-->hemachromatosis


nondegradable endogenous material: alcoholic hyaline aka Mallory's hyaline (which is crosslinked intermediate filaments, crosslinked by acetaldehyde, an aldehyde which comes from teh oxidation of ethanol)

neurofibrillary tangles (1 of 2 major lesions observed in neurons of Alzheimer's)

Front 17

how does the cell respond to injury?

Back 17

hypertrophy (inc cell number)
hyperplasia (inc cell size)
dec cell size ...autophagy
dec cell number...apoptosis


also
production of heat shock proteins

Front 18

name 4 clinical situations where heat shock proteins are induced

Back 18

MI
Crohn's
neuronal hypoxia
adriamycin administration

Front 19

hsp10 and hsp60 are

Back 19

heat shock proteins called chaperones--->help protein folding

Front 20

necrosis based on which 2 interdependent morph changes?

Back 20

enzymatic digestion of the cell constituents and protein denaturation

Front 21

Back 21

Alcoholic hyaline: composed of crosslinked intermediate filaments (prekeratin)

**mallory bodies

Front 22

hallmark of apoptosis

Back 22

endogenous endonuclease cleaves DNA at regular intervals..."ladder" on gel electrophoresis

Front 23

examples of growth factors, when taken away, apoptosis is induced

Back 23

prolactin for breast
estrogen for uterus

Front 24

histological differences bw APOPTOSIS and NECROSIS

Back 24

apoptosis
--no inflammation
--no cell swelling
--represent round masses (some of which contain basophilic condensed chromatin often within phagocytes)
-apoptoic cells dispersed, HARD TO FIND


NECROSIS

-response to injury
--sheets of cells, EASY to see
--eosinophilia of cytoplasm
-usually active inflammation
-swollen cells

Front 25

ultrastructure of apoptosis

Back 25

apoptosis:

chromatin marginates in condensed coarse aggregates, over entire nucleus or large crescentic caps

organelles intact but compacted

surface protrusions seperate to form apoptotic bodies

Front 26

ultrastructure of necrosis

Back 26

chromatin marginates loose aggregates; lysis ensues

organelles disrupted and swollen; characteristc mitochondrial densities (CALCIUM DEPOSITS!)

Front 27

apoptosis:
cellular fragments taken up by

Back 27

single phagocytic cells

Front 28

necrosis:

cellular debris taken up by

Back 28

many macrophages

Front 29

most important difference bw apoptosis and necrosis

Back 29

apoptosis is:

--programmed
--absence of inflammation (surrounding damage)

Front 30

differences in initiation of apoptosis for intrinsic and extrinsic pathways?

Back 30

intrinsic:
release of cytochrome c from intermembrane space of mitochondria into cytoplasm

extrinsic: plasma membrane ligation (TNF or Fas-L)

Front 31

caspases are

Back 31

proteases

Front 32

which caspase mediates extrinsic, intrinsic pathway

execution/effector caspases?

Back 32

caspase 9--intrinsic
caspase 8- extrinsic

caspases 3, 7 are effector

Front 33

apoptotic cells are quickly removed by

Back 33

phagocytosis
(macrophages, dendritic cells)

WITHOUT INFLAMMATION!

Front 34

t/f

the Bcl-2 family of proteins has both pro and ant apoptotic proteins

Back 34

t

Front 35

name some pro and anti apoptotic protiens in the Bcl-2 family

Back 35

survival (anti-apoptotic):
bcl-2
bcl-xl

pro-apoptosis:
bad
bax
bak
bid

Front 36

extrinsic pathway:

the TNF and the Fas receptor have ____ which are signal anchors for adaptor molecules

Back 36

DD; death domains

Front 37

what is the fate of apoptotic cells that aren't phagocytosed?

Back 37

undergo secondary necrosis

Front 38

adaptor molecules of TNF and Fas have what domain that connect to procaspases

Back 38

DED; dead effector domains

Front 39

the _____ domain of adaptor molecules separated from their death effector domains (DED) serve as dominant negative interrupters of cell death

Back 39

death domain

Front 40

why is the liver esp prone to fatty change?

Back 40

bc it produces lipoproteins....so high rate of TG synthesis

Front 41

what could this be? (the bronze/brown deposits)

Back 41

in liver:

could be 1 of 3:
bile, iron, lipofuscin

Front 42

iron is stored by what in the cell?

what carries iron to the cell?

Back 42

ferritin

transferin

Front 43

how do cells respond to stress?

Front 44

hypertrophy:
inc in cell

the opposite of hypertrophy

Back 44

size

autophage (dec in cell size)

Front 45

hyperplasia:
inc in cell

what produces the opposite?

Back 45

number

apoptosis

Front 46

morphological changes of the nucleus during necrosis?

Back 46

pyknosis
karyolysis
karyorrhexis

Front 47

necrosis is cell death following irreversible inury.

what stage is this (of the nucleus?)

dissolution of the nucleus

Back 47

karyolysis

Front 48

nucleus gets small, dense chromatin

Back 48

pyknosis

Front 49

the taking into a cell of exogenous material by phagocytosis or pinocytosis and the digestion of the ingested material after fusion of the newly formed vacuole with a lysosome.

Back 49

heterophagy

Front 50

differences bw reversible and irreversible changes?

Back 50

Front 51

which type of necrosis

Back 51

Two large infarcts of the spleen with “coagulative necrosis”. Etiology of this coagulative necrosis is vascular (with loss of blood supply), so the necrosis occurs in a vascular distribution and has a wedged shape.

Front 52

Back 52

Coagulative Necrosis in a Myocardial Infarct

Front 53

type of necrosis?

Back 53

liquefactive
The brain has little capacity for forming fibrous scars. Loss of blood flow (ischemia) results in liquefactive necrosis and cystic infarcts.

Front 54

which type of necrosis?

where?

Back 54

iquefactive necrosis in the brain due to focal loss of blood supply (ischemia) to a portion of cerebrum. Lesion shows loss of neurons and glial cell reaction, resulting in the formation of the clear space at center left.

Front 55

type of necrosis?

Back 55

Two lung abscesses contain liquefactive necrosis: a liquid center in an area of tissue injury.

Front 56

Back 56

Liquefactive necrosis: often seen in infections (here, an abscess)

Front 57

Back 57

Caseous
necrosis,
tuberculosis:

Similar to coagulative necrosis microscopically, but with a “cheesy” appearance grossly

Front 58

Back 58

Fatty necrosis

Front 59

Back 59

Microscopically, fatty necrosis is basically liquefactive necrosis in which one can see deposits of Ca++ soaps.

Front 60

Back 60

Benign Fat Necrosis in the Breast

(Arrows show Ca++ soaps with foreign body giant cell reaction. There has also been some scarring.)

Front 61

Back 61

Coagulative necrosis in the kidney, due to ischemic necrosis (infarct).

Outlines of glomerulus and tubules can be seen, but cells are dead.

Front 62

Back 62

Coagulative necrosis in the kidney, due to ischemic necrosis (infarct).

Outlines of glomerulus and tubules can be seen, but cells are dead.

Front 63

Back 63

Caseous necrosis in kidney infected by Mycobacterium tuberculosis. Caseous necrosis appears deeply eosinophilic – i.e., compared to the first slide of coagulative necrosis.

Front 64

Back 64

“Gummatous” necrosis, in the liver of a patient with tertiary syphilis (causative agent: Treponema pallidum.)

Front 65

Back 65

Testicular hemorrhage and necrosis, caused by torsion on spermatic cord and obstruction of venous pedicle

Back 66

“Fibrinous” necrosis: a bad term still in use: bright pink staining resembles that of fibrin.

Shown here in an artery of a patient with severe hypertension

Front 67

Back 67

“Fibrinous” necrosis: a bad term still in use: bright pink staining resembles that of fibrin.

Shown here in an artery of a patient with severe hypertension

Front 68

Back 68

salli

Front 69

Necrotic hepatocyte after the “point of no return”

what do you notice?

Back 69

Mitochondria are highly dilated, and contain matrix densities (arrows). The nuclear chromatin is coarse, but in contrast to apoptosis, the pattern is more-or-less that of a normal cell.

Front 70

permeability of mitochondria decreases after injury

t/f

Back 70

false ...increases

(we see mitochondrial swelling)

Front 71

most Ca is sequestered by which 2 cellular organelles

Back 71

mitochondria and ER

Front 72

name 4 effects of an inc intracellular Ca+ concentration

Back 72

Front 73

how does inc intracellular Ca cause membrane damage?

(mainly through 2 ways)

Back 73

Front 74

Even in ischemic necrosis, [O2] ≠ 0, and ______ may occur. Reduced (reactive) oxygen species are among the common agents injuring cells.

Back 74

reperfusion injury

Front 75

Even in ischemic necrosis, [O2] ≠ 0, and ______ may occur. Reduced (reactive) oxygen species are among the common agents injuring cells.

Back 75

reperfusion injury

**when cells are injured, can't really protect itself from oxygen radicals

Front 76

effect of ionizing radiation on proliferating and non proliferating cells?

Back 76

Front 77

what does catalase do and where in the cell?

Back 77

Front 78

what does glutathione peroxidase do?

converts what to what?

Back 78

hydrogen peroxide into 2 waters

Front 79

explain how ischemia (loss of blood supply) could lead to coagulative necrosis?

Back 79

Front 80

how can CCl4 poisoning affect the liver?

Back 80

Front 81

ways in which membrane can be harmed

Back 81

Front 82

Back 82

salli

Front 83

tell me the signalling chain of the extrinsic pathway of apoptosis involving Fas

Back 83

Front 84

which imp transcription factor is pro-survival

Back 84

nf-kappa b

Front 85

signaling chain of intrinsic pathway?

Back 85

Front 86

whats the apoptosome?

Back 86

Front 87

what induces cytochrome c leakage from mitochondria?

Back 87

Front 88

what are some responses to unfolded proteins?

Back 88

Front 89

differences bw apoptosis and autophagy?

Back 89

Front 90

what are some changes that come with aging?

Back 90

Front 91

t/f
there's a decline in maximal oxygen uptake

Back 91

true

Front 92

Exercise protects against secondary aging by reversing

Back 92

abdominal obesity.

Front 93

Abdominal obesity results not so much from high calorie intake, but from ____ and relatively ____ -->abdominal obesity, NIDDM.

Back 93

low physical activity

and

high fat intake

Front 94

with aging, there is accumulation of protein _____ and glycosylation

Back 94

crosslinks


glucose will react with anything that has an amine group-->that's basically all proteins!

Front 95

the extent to which proteins get glycosylated depends on _______

for this reason, diabetics have higher levels of _____ than non-diabetics

Back 95

blood glucose concentration

glycosylated hemoglobin

Front 96

why do diabetics have vascular complications?

Back 96

Front 97

t/f

the less the ROS (reactive oxygen species), the better for the cell

Back 97

false

there's a balance!

Front 98

Major ____ are activated in response to oxidative stress.

Back 98

signalling pathways

Front 99

?

Back 99

lipofuscin

Front 100

lipids get crosslinked through free radical rxns and form

Back 100

lipofuscin

Front 101

lipids get crosslinked through free radical rxns and form

Back 101

lipofuscin

Front 102

abdominal obesity results mainly from genetics and physical inactivity.
_____ may not be as important a factor as the other factors

Back 102

food intake

Front 103

lipofuscin is derived from _____ and accumulates in lysosomes of post-mitotic cells (brain, liver, heart)

Back 103

peroxidized lipids

Front 104

name the 3 enzymes that are the major parts of the antioxidant defense system

Back 104

catalase
superoxide dismutase
glutathione peroxidase

Front 105

HSF1 (heat-shock transcription factor 1) is responsible for activating

Back 105

the heat-shock response

Front 106

oxidative stress
modifies amino acid chains
can cause protein misfolding

also damages what?

Back 106

DNA

Front 107

ROS can originate outside the cell or may be generated intracellulary in response to

Back 107

external stimuli

Front 108

pacemaker theory of aging?

Back 108

a key organ system declines with age and the loss of this function drives the entire aging process

the theories have focused on
1) immune system
2) neuroendocrine system

Front 109

a rhythm that follows the course of a day

Back 109

circadium rhythm

Front 110

In model organisms, Sir2 activity increases in response to calorie restriction, and this is believed to be responsible, in part, for ______

Back 110

increased longevity.

Front 111

what does this say about chromosome 1?

Back 111

Something in chromosome 1 induces aging then…

Front 112

Back 112

Human fibroblasts: “young” cells and “old” cells

The late passage cells show nuclear irregularities and cytoplasmic inclusions – “cellular senescence”.

Front 113

mutation accumulation theory of aging?

Back 113

old age permits accumulation of late-acting deleterious mutations

Front 114

pleiotropic gene theory?

Back 114

genes are selected for benefits early in life even if they have bad effects at later ages

Front 115

disposable soma theory?

Back 115

selection pressure to invest metabolic resources in somatic maintenance and repair is limited

Front 116

in animal testing, there is usually a tradeoff bw longevity and

Back 116

fitness

Front 117

what's the metabolic syndrome (aka dysmetabolic syndrome aka Syndrome X)

Back 117

characterized by obesity, HTN, dyslipidemia, and abnormalities of glucose metabolism

is thought that the obesity-->some insulin resistance (not enough to be diabetes)

they have chronic mild hyperinsulinermia (which is a compensation for insulin resistance)

Front 118

Sir2 homologues in mammals are called?

Back 118

sirtuins (there's 7 of them)

Front 119

cells from patients with progeria--syndromes of accelerated aging--show fewer/more doublings than cells from normal subjects

Back 119

fewer

Front 120

The ____ limit is the number of times a normal cell population will divide before it stops,

Back 120

Hayflick

Front 121

Many progeria syndromes are syndromes of ______

Back 121

genetic instability.

Front 122

14 year old with progeria

Back 122

subhanAllah

Front 123

direction of DNA transcription

Back 123

5-->3

remember thissssss!

Front 124

______ acts as template for reverse transcriptase activity – then translocates to new 3´ end of telomere DNA and repeats the process.

Back 124

Telomerase

(telomerase has RNA)

Front 125

Back 125

Adenoma (benign tumor of epithelial origin, monoclonal proliferation of cells) of pituitary

Front 126

pituitary adenoma can cause what syndrome?

where else can a tumor form that has the same effect

Back 126

cushings

the lungs!

Front 127

Back 127

Cushings!

Front 128

label the different adrenal glands

Back 128

normal
hypertrophy
atrophy

hypertrophy:
The cells are pale bc they have lipid


for the atrophy one:

pituitary resection (was used as treatment for breast cancer)----absence of ACTH…no production of corticosteroids
Faint red line (boundary bw adrenal cortex and medulla)…..so very atrophic gland (due to absence of ACTH)

Front 129

Back 129

acromegaly!
Pituitary adenoma……ACIDIPHILIC pituitary adenoma…..
This is a tumor that produces growth hormone-->acromegaly

Front 130

PTH causes bone ____…increases intestinal _____of Ca too

Bones suffer the most--> osteitis fibrosa (terrible name..it’s not an itis at all)
Hypercalcemia can lead to kidney stones
Calcium in the body of the kidney—______

Back 130

resorption
absorption

nephrocalcinosis

Front 131

Back 131

A: muscle wasting due to cancer
B: Normal heart
C: Hypertrophic heart

Front 132

Back 132

lipofuscin granules

Front 133

The increase in tissue mass in hypertrophy can result from what 2 sources?

Back 133

---Proliferation of remaining cells (example of partial hepatectomy)
Recruitment of stem cells (example of chronic liver injury)

----Many stem cells come from the bone marrow, and can differentiate into specialized cells such as hepatocytes. Underscores plasticity of adult stem cells.

Front 134

Many stem cells come from the bone marrow, and can differentiate into specialized cells such as hepatocytes. Underscores ______ of adult stem cells.

Back 134

plasticity

Front 135

Most pathologic hyperplasia is due to excess of

give 2 examples

Back 135

hormones and growth factors.

1) endometrial hyperplasia:

Normally, after a menstrual period, there is endometrial proliferation induced by estrogen (ovaries) and pituitary hormones.

This stops after 10-14 days because of rising progesterone levels.
An absolute or relative increase in estrogen -->endometrial gland hyperplasia --> abnormal menstrual bleeding.

2) benign prostatic hyperplasia: induced by androgens.

Why are these examples not called neoplasia?

because the process, though abnormal, is controlled. Hyperplasia regresses when hormonal stimuli are eliminated.

Front 136

Adenoma: is ____CLONAL
Hyperplasia: _____CLONAL

Back 136

Adenoma: is MONOCLONAL
Hyperplasia: MULTICLONAL!!

Front 137

which one is normal and which one

Back 137

hyperplastic epidermis (right) in psoriasis (increased numbers of squamous epithelial cells)

Front 138

examples of metaplasia

Back 138

Bone morphogenetic proteins (related to TGF-β) induce bone and cartilage, but suppress fat or muscle differentiation of stem cells.
Retinoic acid regulates cell growth, differentiation, and tissue patterning of stem cells.
Some cytostatic drugs disrupt DNA methylation patterns and can transform fibroblasts to muscle or cartilage

Front 139

smokers usually don't have a lot of

Back 139

cilia

Front 140

t/f
type IV is fibril forming

Back 140

false

Front 141

In triple helix of collagen, every third amino acid must by ____: no room for a b carbon atom. Pro residues favor triple helical structure, OH-Pro make H-bonds with water and amino acids in triple helix.

Back 141

Gly

Front 143

aa sequence of collagen

Back 143

Gly-X-Y

X: often proline
Y: hydroxyproline

Front 144

what does the striated appearance of collagen on EM tell about its packing?

Back 144

Front 145

t/f
the hydroxylation of collagen (of prolines and sometimes lysines) happens after translation

Back 145

true

Front 146

which ECM protein is involved in platelet function, angiogenesis, apoptosis, activation of TGF- and Immune regulation

Back 146

thrombospondin

Front 147

EM glycoproteins that are abundant in embryos and reappear around healing wounds and in the stroma of some tumors.

Back 147

tenascin

(Some tumors have embryo-like phenotypes in certain respects....tenascin is found in the stroma of some tumors)



Tenascin C:
Has anti-adhesive properties. It causes cells to become rounded in tissue culture, perhaps by blocking interaction of fibronectin with cell surface glycosaminoglycans (syndecan).
Tumors expressing high levels of tenascin-C often have a poor prognosis.

Front 148

integrins is a transmembrane protein that connects to ECM proteins on one side and to _______ inside the cell on the other side

Back 148

Front 149

which enzymes degrade ECM

Back 149

matrix metalloproteinases (MMPs).

Front 150

Highly invasive cancers express a LOT of MMP’s

why is this helpful for them?

Back 150

easier to metasize

Front 151

along with being an antibiotic, tetracycline does what to MMPs

metalloproteinases (MMPs): degrade ECM

Back 151

inhibits MMPs

Front 152

osteogenesis imperfecta

Back 152

caused by Type 1 collagen

blue sclerae: you don't have enough collagen....so

perinatal letal: their skeletons are so fragile that they can't even undergo childbirth....usually born still born with like 200 fractures

Front 153

why does heavy ethanol intake cause fatty liver?

Back 153

-->production of glycerophosphate-->inc esterification of fatty acids into TG's

Front 154

which cells are involved in acute and chronic inflammation?

Back 154

The components of acute and chronic inflammatory responses: circulating cells and proteins, cells of blood vessels, and cells and proteins of the extracellular matrix

Front 155

The major local manifestations of acute inflammation include:

Back 155

(1) Vascular dilation and increased blood flow (erythema and warmth),

(2) extravasation and deposition of plasma fluid and proteins (edema), and

(3) leukocyte emigration and accumulation in the site of injury.

Front 156

Vascular changes early in inflammation:

Back 156

-active hyperemia
-peripheral pooling of blood
-leakiness of capillaries and post-capillary venules.



Functional hyperemia, or active hyperemia, is the increased blood flow that occurs when tissue is active.

When cells within the body are active in one way or another, they use more oxygen and fuel, such as glucose or fatty acids, than when they are not. The blood vessels compensate for this metabolism by dilatation, allowing more blood to reach the tissue. This prevents deprivation of the tissue.

Front 157

gaps in blood vessels caused by

Back 157

endothelial cell contraction

Front 158

failure of cell production

Back 158

aplasia

Front 159

during fetal development, aplasia results in

Back 159

agenesis

Front 160

absence of an organ due to failure of production

Back 160

agenesis

Front 161

t/f
hypoplasia is more extreme than agenesis

Back 161

false!
agenesis is more extreme than hypoplasia

Front 162

dec in the size of an organ or tissue resulting from dec in the mass of preexisting cells

Back 162

atrophy

Front 163

associated conditions of squamous metaplasia

Back 163

chronic irritation (eg squamous metaplasia of the bronchi with long-temr use of tobacco) and vitamin A deficiency

Front 164

osseous metaplasia

Back 164

formation of new bone at sites of tissue injury

Front 165

myeloid metaplasia (extramedullary hematopoiesis)

Back 165

proliferation of hematopoietic tissue at sites other than the bone marrow, such as the liver or spleen

Front 166

in early stage hypoxic cell injury, what's the cause of :
-cellular swelling (or hydropic change)
-ER swelling
-mitochondria swelling

Back 166

low production of ATP-->reduced activity of Na-K-ATPase

Front 167

what's the point of no return, after which cell death is imminent

Back 167

irreversible damage to cell membranes
massive calcium flux
extensive calcification of the mitochondria

Front 168

t/f
neurons are more vulnerable to hypoxic injury than myocardial cells

Back 168

true

Front 169

which type of necrosis:

results from interruption of blood supply

Back 169

coagulative necrosis

Front 170

which type of necrosis:

tuberculosis is the leading cause

Back 170

caseous

Front 171

type of necrosis most often affects the lower extremities or bowel and is secondary to vascular occulsion

Back 171

gangrenous necrosis