Path Exam 3 Flashcards
(681 cards)
1
Q
Autosomal recessive polycystic kidney disease
A
Enlarged kidneys composed of saccular or cylindrical cysts
Replace renal parenchyma
2
Q
when does Autosomal recessive polycystic kidney disease present
A
Usually presents in prenatal period, can present in childhood
3
Q
other effects of Autosomal recessive polycystic kidney disease
A
Can prevent lung development → stillborn, or die shortly after birth
Cysts and bile duct proliferation are seen in the liver
4
Q
effects of juvenile onset of Autosomal recessive polycystic kidney disease
A
hepatic fibrosis and disease is dominated by liver manifestations
5
Q
Autosomal dominant polycystic kidney disease
A
Genetic disease with high penetrance
Kidneys greatly enlarged with numerous cysts
Pressure atrophy effects from cysts tubules and vessels
6
Q
what do most cases of Autosomal dominant polycystic kidney disease result from?
A
gene defects on chromosome 16
7
Q
when does Autosomal dominant polycystic kidney disease present?
A
mid- adulthood but may manifest in perinatal period or in old age
8
Q
treatment for Autosomal dominant polycystic kidney disease
A
transplant
dialysis
9
Q
what can chronic dialysis cause?
A
atrophy of kidney
many small cysts
10
Q
what can cause acquired cysts?
A
long term dialysis patients
11
Q
simple cysts
A
Single or multiple cysts, translucent, filled with clear fluid and lined by single layer of simple epithelial cells
12
Q
when can simple cysts become problematic?
A
large cysts may rupture, hemorrhage
13
Q
Glomerulonephritis
A
Inflammatory disease of the glomeruli that can show different patterns of glomerular injury
14
Q
Glomerulonephritis symptoms
A
asymptomatic hematuria or proteinuria
nephrotic syndrome
nephritic syndrome
acute renal failure
15
Q
nephrotic syndrome
A
marked proteinuria that is indicative of significant dysfunction of glomerular ultrafiltration
16
Q
nephritic syndrome
A
presence of red blood cell casts in the urine that is indicative of severe glomerular injury
17
Q
diffuse
A
most or all glomeruli are affected by disease
18
Q
focal
A
only some glomeruli are affected by disease
19
Q
segmental
A
only part of the glomeruli is affected by disease
20
Q
global
A
entire glomeruli is affected by disease
21
Q
normal glomerulus
A
Highly specialized filter in which the blood in the capillaries are filtered through epithelium, BM, and endothelium
22
Q
type 1 mesangial cells
A
contractile
23
Q
type 2 mesangial cells
A
phagocytic
secretory
24
Q
features of endothelial cells of glomeruli
A
fenestrated with 70-100 nm pores
Anionic charges restrict negatively charged molecules
Size filter restricts proteins that are around the size of albumin
25
what composes the glomerualar BM?
collagen type IV, laminin, polyanionic proteoglycans, fibronectin, glycoproteins
26
role of glomerualar BM
size charge and filter
27
Visceral epithelial cell
podocyte with complex interdigitating processes
28
Bowman’s space
space for pre-urine ultrafiltrate from capillary loops
29
Parietal epithelium
epithelial cells lining Bowman’s space
30
3 mechanisms of immune injury within the glomerulus
Immune complexes formed within the glomerulus → anti-glomerular BM antibodies
Immune complexes formed outside the glomerulus and trapped by the glomerulus
Activation of immune response not involving antigen-antibody formation
31
Mesangial cell hypercellularity clinical correlation
hematuria
32
Mesangial matrix increase clinical correlation
decreased GFR
33
Epithelial cell foot process effacement clinical correlation
proteinuria
34
Crescent formation clinical correlation
acute renal failure
35
Pyelonephritis
Inflammation of the renal parenchyma, calyces and renal pelvis as a result of infection
36
acute pyelonephritis
Ascending bacterial infection from the bladder
37
Hematogenous seeding
Infection elsewhere in body that travels to kidney
38
what can hematogenous seeding lead to?
obstructed kidney
39
who is more prone to acute pyelonephritis
diabetics
40
___ papillae are convex and resist reflux urine
Renal
41
___ papillae are concave and allow easier access
compound
42
chronic pyelonephritis
Chronic tubulointerstitial disease with gross, irregular, and often asymmetric scarring and deformation of the calyces
43
gross appearance of chronic pyelonephritis
Dilated calyces
| Opaque urethral membranes
44
features of end stage renal failure
```
Tubules dilated with hyaline casts → “thyroidization” of kidney
Chronic inflammatory cells
Thickening of vessels
Fibrosis
Global sclerosis
```
45
global sclerosis
all scared, non functional glomeruli
46
what can scar tissue in the kidney lead to?
loss of renal cortex
47
calculi
renal stones
48
intrinsic obstructive lesions
calculi
strictures
tumors
blood clots
49
extrinsic obstructive lesions
pregnancy
endometriosis
tumor
50
Sclerosing retroperitonitis
Produces ill-defined fibrous masses with pronounced chronic inflammatory response
51
treatment for kidney stones
sound waves
| can pass on their own
52
most common patients with bladder outflow obstruction
elderly males due to prostatic hypertrophy or disease
53
80% of all malignant tumors are ___
renal cell carcinoma
54
renal cell carcinoma is ___% of all cancers
1-3
55
when do cases of renal cell carcinoma peak?
6th and 7th decade
56
hypernephroma
renal cell carcinoma
57
adenocarcinoma of kidney
renal cell carcinoma
58
renal cell carcinoma etiology
increased in smokers
| chromosome abnormalities in 3,8, 11
59
renal cell carcinoma sites
more common in upper pole
60
gross appearance of renal cell carcinoma
spherical
hemorrhagic or cystic
usually large size 3-15cm
61
where do renal cell carcinoma tend to invade?
renal vein
| can stretch to atria
62
microscopic appearance of renal cell carcinoma
commonly composed of large clear or granular cells
| Areas of hemorrhage and necrosis are common
63
Small basophilic cells with papillary patterns tend to have ___
chromosomal trisomies
64
large chromophobic cells tend to have ____
chromosome deletions
65
sacromatoid pattern cells tend to have ___
multiple cytogenic abnormalities
66
which cells in renal cell carcinoma have a poorer prognosis?
sarcomatoid pattern cells
67
complications of renal cell carcinoma
metastasis, commonly to lungs and bone
| Paraneoplastic syndromes from secretion of active compounds
68
secretion of erythropoietin from renal cell carcinoma causes ___
polycythemia
69
secretion of parathormone from renal cell carcinoma causes ___
hypercalcemia
70
secretion of renin from renal cell carcinoma causes ___
hypertension
71
secretion of ACTH from renal cell carcinoma causes ___
cushing's syndrome
72
signs and symptoms of renal cell carcinoma
```
painless hematuria
flank pain or mass
malaise
weakness
weight loss
```
73
how to clinically diagnosis renal cell carcinoma
X-ray
CAT
MRI
surgical exploration
74
how to lab diagnosis renal cell carcinoma
histologic examination
75
renal cell carcinoma treatment
nephrectomy
| chemotherapy
76
Transitional cell carcinoma usually arises in ___
the bladder
77
Transitional cell carcinoma is _% of all cancers
2-3
78
Transitional cell carcinoma risk factors
Occupational exposure to naphol and some phenols
Tryptophan
Cigarette smoking
Treatment with cyclophosphamide
79
gross appearance of transitional cell carcinoma
Flat pattern with plaque like thickenings
| Fingerlike papillary projections
80
microscopic appearance of transitional cell carcinoma low grade/grade 1
resemble normal transitional cell epithelium
81
microscopic appearance of transitional cell carcinoma high grade/grade 3
anaplastic
82
when is transitional cell carcinoma considered invaded?
penetration of BM
83
pre-neoplastic changes in transitional cell carcinoma
Hyperplastic
dysplasia
carcinoma-in-situ are commonly seen in uninvolved areas of bladder mucosa
84
carcinoma in situ
anaplastic, malignant cells with mitoses confined completely to the mucosa
85
____ is a precursor lesion of invasice TCC
carcinoma in situ
86
Hyperplasia of the transitional epithelium
increase in number of cell layers >7
87
Dysplasia of transitional epithelium
Cytological atypia and mitotic activity within transitional epithelium
Changes with or without hyperplasia
Cells lose polarity
88
clinical course of TCC
painless hematuria
89
what is Wilms tumor associated with
abnormality on chromosome 11
90
what does wilms tumor look like?
primitive kidney
91
prostate
retroperitoneal organ that encircles the neck of the bladder and urethra
92
2 layers of prostate
basal layer of low columnar epithelium
| Columnar, mucus secreting epithelium
93
if ____ is missing in the prostate, indicates cancer
basal layer of epithelium
94
where do most prostate cancers occur?
peripheral zone
95
where does BPH occur in the prostate?
central zone
96
what is the most common cancer in the US?
Prostatic adenocarcinoma
97
who is most at risk for Prostatic adenocarcinoma?
age >60
| African Americans
98
gross appearance of Prostatic adenocarcinoma
gritty and firm, poorly demarcated
Can infiltrate adjacent structures
Occurs in peripheral areas and posterior lobe of prostate
Usually yellowish or white-grey
99
histology of prostatic adenocarcinoma
glandular pattern with small disorganized gland architecture
Single cell layer of epithelium, no basal layer
Papillary or cribriform pattern
100
gleason score
Grade (1-5) + grade (1-5) = Score (2-10)
| primary pattern and secondary pattern
101
what is staging of prostatic adenocarcinoma based on?
degrees of access of tumor to different body parts
102
stage I-II of prostatic adenocarcinoma
confined to prostate
| Curable
103
stage IV of prostatic adenocarcinoma
pelvic node or other metastatic lesions
| 80% here when symptoms occur
104
symptoms of stage IV of prostatic adenocarcinoma
Pain
hematuria
dysuria,
frequency or urinary flow problems
105
where does prostatic adenocarcinoma metastasize
bone
106
prostatic adenocarcinoma treatment
surgery
castration
radiation
hormonal treatment
107
Prostatic intraepithelial neoplasia
Precursor to malignancy of the prostate
| Prostatic glands with intact basal layer, increased # and stratification of cells lining glands
108
when does Prostatic intraepithelial neoplasia incidence increase?
age 40
| 10 years before increase in cancer
109
G1 Phase
```
Cell grows in size
Monitors availability of growth factors, nutrients, amino acids, whether or not there is room to grow
Makes ultimate “go, no go” decision
Restriction; point of no return
6-12 hours
```
110
S phase
Replication of all genomic DNA
Accurate but not perfect
Proofreading and error correction mechanisms exist
6-12 hours
111
G2 phase
Cell continues to grow in size
Cell synthesizes all of proteins necessary for mitosis
2-4 hours
112
M Phase
Mitosis
Replicated chromosomes are equally segregated into 2 daughter cells
Stressful to cell
Only lasts 15-45 minutes
113
loss of ____ is a hallmark of all human cancers
G1/S regulation
114
pro-growth factors
RTKs
MAPK
PI3K
115
anti-proliferative factors
p52
Rb
PTEN
p16
116
RTKs are bound by ___
growth factors
117
RTK cascades lead to transcription of genes important for growth such as:
myc
| cyclin D
118
Elevated Cyclin D proteins binds and activates ___
Cdk4/6 kinases
119
Active cyclin D:Cdk4/6 complexes phosphorylate Rb protein, which sequesters ____
E2F transcription factors
120
E2F drive expression of?
genes necessary for S phase
121
oncogenes
genes that when activated/overexpressed promote cancer
122
tumor suppressors
genes whose functional loss promotes cancer
123
what is Rb
E2F inhibitor
124
what is p53
transcription factor
125
what is PTEN
PI3K inhibitor
126
what is p16
Cdk inhibitor
127
mutation
change in the nucleotide sequence of an organism
128
most common BRAF mutation
single nucleotide change from T to A at 1799
129
endogenous factors that contribute to cancer
ROS
| DNA replication mistakes
130
__% of cancer driving mutations arise from normal mutation rates
66
131
__ DNA repair genes in humans
150
132
BRCA mutation
predisposes women to breast and ovarian cancers
133
what is aneuploidy a consequence of?
abnormal mitosis
134
aneuploid
possessing an abnormal number/structure of chromosomes
135
aneuploidy can ___ oncogenes
amplify
136
aneuploidy can __ tumor suppressor genes
deplete
137
multi hit hypothesis
Multiple genetic changes are required for tumorigenesis
activation of an oncogene
loss of a tumor suppressor
replicative immortality
138
how many genetic changes for tumorigenesis to start?
4-6
139
why are oncogene specific inhibitors failing in trials?
developed resistance
140
Metastasis
spread of cancer cells from 1 organ to another via the bloodstream
141
how do tumors achieve immortality
expression of telomerase
142
what happens when solid tumors cause inflammation?
immune cells release ROS and cytokines
143
how do tumors avoid apoptosis?
overexpressing anti-apoptotic proteins
144
why do cancer cells have increased rates of glycolysis?
need to synthesize building blocks for rapid growth
145
goal of targeted therapeutics and personalized medicine in cancer
identify the relevant driving mutations in individual patients
146
neoplasia
The process of uncoordinated cell growth exceeding the limits established for normal tissues due to loss of responsiveness to normal growth conditions
147
tumor
Swelling that can be produced by edema, hemorrhage, or neoplasm
148
hyperplasia
An increase in the # of cells comprising a tissue or organ
149
hypertrophy
Increase in size of individual cells making up a particular tissue or organ
150
metaplasia
Reversible change from one adult cell type to another adult type
151
are metaplastic changes precancerous?
no but can lead to cancerous transformation
152
dysplasia
Loss of normal orientation of one epithelial cell to the other
Accompanied by alterations in cell size and shape, nuclear size and shape, mitotic activity and staining characteristics
153
where is dysplasia usually occur?
lining epithelia
154
are dysplasia changes precancerous?
yes
| assoc with anaplasi
155
anaplasia
lack differentiation
156
what marks anaplastic changes?
```
Pleomorphism
Nuclear pleomorphism
Increased nuclear:cytoplasm ratio
abundant/abnormal DNA content
Aneuploidy
Presence of prominent nucleoli
Increased mitotic activity
Tumors giant cell formation
```
157
how are tumor giant cell forms?
Result of nucleus dividing but cytoplasm not dividing
158
differentiation
Extent to which parenchymal cells of a particular growth resemble the normal cells in the tissue or organ from which the growth arose both morphologically and functionally
159
well differentiated tumors
cells that closely resemble normal cells of parent organ/tissue
160
poorly differentiated tumors
more primitive appearance
161
what is the degree of differentiation of glandular neoplasms dependent on?
Degree of differentiation is determined by ability of tumor cells to form well-defined glands or to occur in solid sheets with minimal gland formation
162
what is the degree of differentiation of squamous epithelial tumors dependent on?
Degree of differentiation depends on extent of keratinization
163
2 basic divisions of neoplasms
benign
| malignant
164
benign neoplasms
Abnormal growth of cells that cytologically closely resembles the normal cells of the tissue from which the tumor arises
165
what suffix denotes benign neoplasms?
oma
166
Benign tumor of fibroblasts
fibroma
167
Benign tumor of smooth muscle cells
leiomyoma
168
Benign tumor of chondrocytes
chondroma
169
Benign tumors of gland forming cells
adenomas
170
where do benign tumors of gland forming cells form tubular structures?
colon
kidney
thyroid
171
where do benign tumors of gland forming cells form solid sheet?
adrenal cortex
| liver
172
cysadenoma
large ovarian cysts
173
Benign tumors of squamous epithelium
epitheliomas or papillomas
174
verruca
wart
175
polyp
tumor that projects above a mucosal surface
176
where are glandular polyps?
colon
177
where are squamous polyps?
vocal cord
178
teratomas
tumors that arise from germ cells
179
hamartoma
results from disorganized collection of normal tissue
180
Benign tumor of meninges
meningioma
181
Benign tumor of ependymal cells in 3rd ventricle
ependymoma
182
2 fundamental properties define a tumor as malignant
Invasion and destruction of adjacent tissues
| Spread to distant sites → metastasis
183
Malignant tumors of mesenchymal tissue
sarcomas
184
Malignant tumors of fibroblasts
fibrosarcoma
185
Malignant tumor of chondrocytes
chondrosarcoma
186
Malignant tumor of smooth muscle
leiomyosarcoma
187
Malignant tumors of epithelial cells
carcinomas
188
Malignant tumors of squamous epithelial cells
squamous cell carcinomas or epidermoid carcinomas
189
Malignant tumors of glandular epithelial cells
adenocarcinomas
190
Malignant tumors of transitional epithelial cells
transitional cell carcinomas
191
grade 1 tumor
well differentiated
closely resemble parent cell of origin
less aggressive behavior
192
grade 3 tumor
poorly differentiated
departs from normal
aggressive behavior
193
what does the stage of a tumor tell you?
stage
194
what does tumor staging take into account?
Local growth → size, contiguous invasion
Lymph node metastasis
Distant metastasis
195
T of TNM cancer staging system
primary size of tumor
196
N of TNM cancer staging system
of node metastases
197
M of TNM cancer staging system
presence and extent of distant metastases
198
__ staging for colon adenocarcinoma
Duke
199
___ classification of melanomas of skin
Breslow and Clark
200
__ staging for ovarian carcinoma
FIGO
201
___ classification for lymphoid malignancies
Ann Arbor
202
most frequency cause of death due to cancer
colorectal carcinoma
203
pre invasive neoplasm of colorectal cancer
adenoma or polyp
204
when does risk for colorectal cancer start?
age 50
205
cumulative life risk for colorectal cancer
5%
206
60-80% of colorectal cancers are the ___ pathway
classical, APC
207
how does the classical pathway of colorectal originate?
bi-allelic mutation of the APC gene in a stem cell of the colonic mucosal crypt
208
classical pathway colorectal cancer mutation
crypt cell produces truncated version of APC protein
209
what critical function is lost because of the classical pathway of colorectal cancer?
function of sequestering beta catenin
210
what is the earliest stage of classical colorectal cancer?
one or a small # of effected crypts
| adenoma
211
formation of small dysplastic polyp leads to formation of ___
tubular adenoma
212
what is upregulated in tubular adenomas of colorectal cancer?
COX2 enzyme activity that inhibits apoptosis
213
Mutations of ___ are acquired in polyps that increase in size
oncogene Kras
214
adenomatous phenotype
adenomas show low-grade dysplasia
215
High grade dysplasia is present when there is _____
increased nuclear atypia and extreme gland architectural abnormality
216
APC pathway is associated with __ mutation
p53
217
PIK3CA mutation is present in _% of CRC
15-25
218
what is the marker for COX2 mutation in CRC?
PIK3CA mutation
219
Specific region on ___ is deleted in ~75% of colon cancers and in 50% of advanced adenomas
chromosome 18q
| encompasses a suppressor gene
220
what characterizes the endpoint of the classical CRC pathway?
MSS
| chromosomal instability
221
where is classical CRC found?
distal colon
| rectum
222
appearance of classical CRC
flat, plaque-like, ulcerated or polypoid
223
histological appearance of classical CRC
moderately differentiated
| grade 2-3/4
224
___ pathway accounts for 20-30% of colorectal adenocarcinomas
serrated polyp
225
appearance of serrated poylp CRC
series of polyps that have glands or crypts with a characteristic saw tooth/serrated outline
226
how does serrated polyp CRC originate?
crypt stem cell that develops an activating mutation of an oncogene in the RAS-RAF-MAPK intracellular signaling pathway
227
senescence
crypts enlarged to accommodate colonocytes that have normal nuclei but increased cytoplasmic volume and reduced tendency to slough into the lumen
228
BRAF mutation CRC
marked serration of crypts
Cytoplasm of cell is filled with small mucin vacuoles
Microvesicular serrated polyp
229
Microvesicular serrated polyp appearance
Predominance of microvesicular cells
| Serration extending deeply but not to crypt base
230
KRAS mutation CRC
less prominent serration
Marked by tufting of surface
Increased number of goblet cells
Goblet cell serrated polyp
231
where do hyperplastic polyps occur
distal colon
| rectum
232
what is upregulated in hyperplastic polyps?
cell cycle inhibitors → p16, p14
233
what can happen to BRAF mutated hyperplastic polyps?
develop disordered growth → atypical variant called sessile serrated adenoma (SSA)
234
dysplastic serrated polyp
sessile serrated adenoma with cytological dysplasia
| This can develop into cancer
235
Endpoint carcinomas of BRAF mutation are ___ located and show ____
proximally
| microsatellite instability
236
what drives BRAF mutation
epigenetic process of CpG methylation
237
what leads to microsatellite instability?
mismatch repair gene hMLH1 becomes inactivated due to bi-allelic methylation of its promoter region
238
what is the equivalent of p53 mutation of APC pathway in the serrated pathway?
development of microsatellite instability
239
location of serrated polyp BRAFmut CRC
proximally
240
mean age of serrated polyp CRC
later than APC
| 76
241
histologic appearance of serrated pathway CRC
Serrated glands/undifferentiated
Mucin
Lymphocytic response
242
which has more CpG island methylation BRAF or KRASmut?
KRAS
243
which occurs more proximally BRAF or KRASmut?
BRAFmut
244
environmental pathology
disorders that occur because of exposure to harmful chemical and physical agents in the immediate environment
245
toxicology
study of harmful agents and their distribution, effects, and mechanisms of action
246
xenobiotics
environmental chemical agents
247
how are xenobiotics metabolized?
cytochrome P450 enzymes
248
particulates
Combustion particles and mineral dusts derived from major compounds in the earth → coal, silica and iron
249
when are particulates harmful?
<10um diameter
| too small to be trapped by the nasal hairs or mucociliary lung epithelium
250
what happens after particulates are phagocytosed?
Release inflammatory mediators that may cause lung damage
| Can lead to heart rate irregularities
251
main outdoor air pollutants
```
particulates
sulfur dioxide
CO
ground level ozone
nitrogen dioxide
```
252
symptoms of mild CO poisoning
dizziness
confusion
headache
253
symptoms of severe CO poisoning
depression of CNS
heart damage
death
254
what generates ground level ozone
photochemical reaction between NOs with UV light
255
adverse effects of ground level ozone
Forms free radicals → inflammation, damage lung epithelium
256
what can smog cause?
inflammation
| lung damage
257
formaldehyde sources
foam insulation
glues
wood
258
formaldehyde toxic effect
asthma
eye/nose/throat irritation
contact dermatitis
nasopharyngeal cancer
259
asbestos source
insulation
| floor and ceiling tiles
260
asbestos toxic effect
mesothelioma
lung fibrosis
lung cancer
261
radon source
soil
| uranium mines
262
radon toxic effect
lung cancer
263
lead source
water
lead paints
leaded gas
264
lead toxic effect
```
hematologic
skeletal
neurologic
GI
renal
more in children than adults
```
265
lead mechanism of toxicity
binds to sulfhydryl groups in proteins and blocks Ca metabolism
266
mercury source
contaminated fish
| dental amalgums
267
mercury toxic effect
tremors
confusion
mental retardation
death
268
mercury mechanism of toxicity
binds to sulfhydryl groups in proteins
| esp in CNS and kidney
269
arsenic source
soil
water
wood preservers
herbicides
270
arsenic toxic effect
```
acute GI
CVS and CNS damage
hyperpigmentation
hyperkeratosis
lung, bladder, skin cancers
```
271
arsenic mechanism of toxicity
trivalent arsenic replaces phosphates in ATP which inhibits mito ox phos
272
cadmium source
nickel cadmium batteries get into water, soil, food
273
cadmium toxic effect
obstructive lung disease
kidney damage
lung cancer
274
cadmium mechanism of toxicity
increased ROS?
275
lead effects on bone
lead lines
| poor remodeling of cartilage and bone trabeculae
276
burtonian line
characteristic blue line at the junction of the gums and teeth due to deposition of sulfate in lead poisoning
277
volatile organic compounds
choloform
carbon tetrachloride
benzene
1,3 butadiene
278
where do you find carbon tetrachloride?
degreasing agents → dry cleaning, paint remover
279
where do you find benzene and 1,3 butadiene?
Used in manufacturing of plastics, lubricants, rubbers, and dyes
280
how do volatile organic compounds enter the body?
lungs
281
symptoms of volatile organic compounds
headache
| dizziness
282
chronic exposure to volatile organic compounds causes?
impaired liver and kidney function
283
organochlorines
polychlorinated biphenyls
dioxin
DDT
284
organochlorines source
old capacitors and transformers
incompletely incinerated waste
pesticides
285
organochlorines toxic effect
chloracne
rashes
liver damage
endocrine disorder
286
organochlorines mechanism
probable carcinogens bind to aryl hydrocarbon R on cells and cause transcriptional changes
287
vinyl chloride source
manufacturing of polyvinylchloride products
288
vinyl chloride toxic effect
liver angiosarcoma
289
vinyl chloride toxic mechanism
processing of metabolites in liver
290
phthalate esters source
flexible plastics
291
phthalate esters toxic effect
reproductive toxin in animals
292
BPA source
bottles
| coating of cans
293
BPA mechanism and effect
estrogen mimic
| proliferative effect
294
chloracne
acne-like eruption of cysts, hyperpigmentation, hyperkeratosis
295
what causes 90% of lung cancers?
cigarette smoking
296
Life expectancy for smokers is __ years lower
10
297
how does nicotine work?
Binds to nicotinic ACh R in the brain → release of catecholamines from sympathetic neurons → increased HR, BP, CO
298
Polycyclic hydrocarbons
toxic compound in cigarettes
Bind to aryl/aromatic hydrocarbon R
carcinogen
299
nitrosamines
toxic compound in cigarettes
| Associated with increased risk of gastric cancer
300
why are smokers at increased risk for MI?
Toxins injure endothelial cells → atherosclerosis
301
why are smokers at increased risk for chronic bronchitis?
Tar, formaldehyde, NOs → irritants → inflammation with mucus production → chronic bronchitis
302
why are smokers at increased risk for emphysema?
inflammatory mediators in the lung recruit neutrophils that produce elastase → destroys elastin in alveolar walls
Leads to enlarged air spaces
insufficient gas exchange and impaired respiratory function → irreversible lung disease called emphysema
303
Chronic bronchitis and emphysema → ?
COPD
304
ADH decreases __
NAD
305
what does ADH form?
toxic acetaldehyde
306
why is acetaldehyde toxic?
Carcinogen that acts by interfering with DNA replication and repair
Contributes to incoordination, memory impairment, sleepiness, facial flushing, nausea, rapid HR
307
what does ALDH form?
converts acetaldehyde into acetic acid
308
what cofactor does ALDH use?
NAD
309
what do variants of ADH and ALDH enzymes cause?
acetaldehyde level and tolerance to alcohol
310
effects of fast ADH and/or slow ALDH
higher levels of acetaldehyde
Lower tolerance to alcohol
Protects against alcoholism
311
BAC of 200 mg/dL → ?
drowsiness
312
BAC >300 mg/dL → ?
stupor with greatly diminished responsiveness
313
acute alcoholism
1 time high alcohol consumption
314
effects of acute alcoholism
```
Affects CNS
Depression of neuronal centers
Reversible liver and stomach damage can occur
Fat accumulation in hepatocytes
Gastritis, ulceration
```
315
chronic alcoholism
repeated long-term high alcohol consumption
316
liver effects of chronic alcoholism
Liver shows fatty change and alcoholic hepatitis (inflammation of liver)
Progresses to fibrosis and cirrhosis → irreversible replacement of hepatocytes by scar tissue
Impairs blood flow through liver → portal hypertension with large swollen veins in GI
These varices can rupture → internal bleeding with life threatening complications
317
fetal alcohol syndrome
From consumption of alcohol during pregnancy, especially in the 1st trimester
318
fetal alcohol syndrome symptoms
Microcephaly
Facial abnormalities
Growth retardation
Reduced mental functioning
319
fetal alcohol syndrome incidence
3/1000 children in US
320
leading cause of death for those <44
Unintentional injuries
321
mechanical injury
whenever a force of sufficient magnitude is applied to the body
322
most significant sites of mechanical injury
Soft tissues
bones
head
323
abrasion
scraping or rubbing
| removes superficial layer of skin
324
contusion
bruise from a blunt object
| extravasation of blood into tissue
325
laceration
tear or disruptive stretching from a blunt object
| intact bridging blood vessels
326
incised wound
from a sharp object
| severed bridging blood vessels
327
puncture wound
pierced tissue from penetration of a long and narrow sharp object
328
when is a puncture wound perforating?
if exit wound if formed
329
what determines clinical significance of thermal burns?
Depth of burn
% of body surface involved
Presence of internal injuries from inhalation of hot and toxic fumes
Promptness and efficacy of therapy
330
superficial burn
Limited to epidermis
Appears red and dry
Painful
331
partial thickness burn
Destroys the epidermis and part of the dermis
Read and moist with blisters
Painful
332
full thickness burn
Destroys epidermis and dermis
Anesthetic → not painful because nerve endings in skin are destroyed
Not capable of regeneration
Pose high risk of infection
333
hyperthermia
Consequence of prolonged exposure to high ambient temperature
334
heat cramps
occur as a result of loss of electrolytes via sweating
335
heat exhaustion
most common, manifestation as prostration (extreme physical weakness) and a brief period of collapse
336
what causes heat exhaustion
hypovolemia caused by dehydration
337
heat stroke
cessation of sweating due to failure of thermoregulatory mechanisms with prolonged core temperature >40 C
338
why is heat stroke the most serious hyperthermia?
Leads to peripheral vasodilation
| Can lead to reduced blood flow to the brain and heart → confusion, coma, death
339
hypothermia
Consequence of prolonged exposure to low ambient temperature
340
mild hypothermia
32-35 C core temp
Hyperventilation
lethargy
vigorous shivering to generate heat
341
moderate hypothermia
28-32 C core temp
Hypoventilation
confusion
loss of coordination
342
severe hypthermia
<28 C core temp
Unconsciousness
slow or no breathing
low or no pulse
343
effects of local hypothermia
```
frostbite
trench foot (gangrene)
```
344
how does frostbite occur?
Suppression of vital metabolism
Crystallization of intra and extracellular water
Increased permeability of vessels
Ischemia, hypoxia, infarction
345
Wet skin lowers resistance to the conductance of the current ___
100x
346
what determines severity of electrical injury?
type and intensity of current
path of current
resistance of tissue
duration of exposure
347
types of electrical injury
Burns at entry and exit sites and internal organs
ventricular fibrillation or cardiac and respiratory center failure
paralysis of medullary centers and extensive burns from high voltage current
348
what can AC current cause?
tetanic muscle spasms, prolonged clutching of current source → asphyxia from spasm of chest wall muscle
349
particulate radiation
Arises from nuclear decay and comprises alpha and beta particles and neutrons
350
ionizing forms of radiation
X-rays and gamma rays, and alpha, beta and neutron particles
351
what does ionizing radiation induce formation of?
free radicals by molecules with which they collide
352
ionizing radiation is ___
mutagenic
353
how does ionizing radiation cause mutation?
directly by free radical formation in DNA and indirectly by inducing other free radicals (ROS)
If DNA is not repaired → mutations lead to cell death or contribute to carcinogenesis
354
cells with highest sensitivity to ionizing radiation
rapidly dividing cells → lymphoid cells, hematopoietic cells, germ cells, and GI epithelium
355
rapidly dividing cells die when exposed to __SV
<25
356
cells with moderate sensitivity to ionizing radiation
Skin
blood vessels
squamous epithelium
growing bone and cartilage
357
cells with lowest sensitivity to ionizing radiation
```
kidney
muscle
brain
endocrine organs
adult bone and cartilage
```
358
injuries from ionizing radiation
Vascular damage
inflammation
Fibrosis
Radiopneumonitis in the lungs
359
Radiopneumonitis
Alveolar spaces are filled with CT
360
most energetic and harmful UV
UVC
361
ozone layer absorbs which UV?
UVC
362
UVB causes?
Causes dimerization of pyrimidines in DNA → transcriptional errors → cancer
363
UVS causes ____ damage
non neoplastic
364
sun burn symptoms
Erythema → reddening of skin
Pigmentation → tanning
Depletion of Langerhans cells
All these changes are reversible
365
long term exposure to UVA causes?
irreversible degeneration of skin elastin and collagen → wrinkles, leathery skin
increased risk of cataracts
366
what can high electromagnetic field radiation cause?
burns and possibly cancer
367
what gives off electromagnetic field radiation
radiowaves
| microwaves
368
anemia
reduction in oxygen carrying capacity of blood
369
what is the most common form of nutritional deficiency?
anemia
370
total body iron in women
2g
371
total body iron in men
6g
372
__% of iron is in Hb
80
373
storage pool of iron
ferritin, hemosiderin
374
transport of iron
transferrin
375
what regulates iron balance?
absorption of dietary iron
376
Most iron required to maintain erythron is salvaged from ___
the turnover of senescent RBCs
377
Daily loss of iron
1-2 mg/day through shedding of mucosal and skin cells
378
primary iron absorption site
duodenum
379
causes of iron deficiency anemia
low intake
malabsorption
increased demand
chronic blood loss
380
Sprue
inflammation of duodenum, loss of villi
381
most common cause of iron deficiency anemia in western world
chronic blood loss from ulcers, tumors, dysfunctional uterine bleeding
382
Megaloblastic anemia
Condition where RBC are larger than normal with a hypercellular bone marrow
383
what can cause Megaloblastic anemia
dietary deficiency of vitamin B12 or folic acid
| pernicious anemia
384
Pernicious Anemia
A megaloblastic anemia associated with atrophic gastritis
| Complete achlorhydria and malabsorption of vitamin B12 due to a deficiency of intrinsic factor
385
source of B12 in diet
animal products
386
how is B12 absorbed in salivary gland?
R binders
387
what 2 rxns require B12?
Methyltransferase in conversion of homocysteine → methionine
Isomerization of methylmalonyl coenzyme A to succinyl coenzyme A
388
Atrophic gastritis
Chronic inflammation of mucosa associated with atrophy of glands and intestinal metaplasia
389
most common autoantibodies in pernicious anemia
90% → antiparietal cell antibodies
75% → anti-IF antibodies
50% → antibodies to thyroid tissue
390
risk factors for PA
Northern Europeans
More common in males
50-80 years old
391
Atrophic glossitis
shiny, glazed, depapillated tongue
392
GI tract symptoms of PA
Epithelial atrophy
Atrophic glossitis
Atrophic gastritis
393
what is seen in the bone marrow of PA pts
```
hypercellular
erythroid hyperplasia, megaloblasts
nuclear/cytoplasmic dyssynchrony
giant metamyelocytes
Larger cells, neutrophils with more lobes
```
394
what is seen in the peripheral smear of PA pts
macroovalocytes
hypersegmented polys
giant platelets
395
neurologic symptoms of PA
symmetric numbness and tingling of extremities
impaired vibratory and position sense
spastic ataxia
Degeneration of posterior and lateral columns of the spinal cord
396
lab tests for PA
serum B12
| schilling test
397
serum B12 test
measured by radioisotope dilution assay
| <100 confirms PA
398
schilling test
measures absorption of labeled vitamin B12
| repeat test with IF to confirm PA
399
PA therapy
Lifelong therapy with B12
Initial dose of 1000 ug
1000 ug weekly, then every month for life
~10-15% of administered dose is retained
400
why is folate important?
Folic acid acts an intermediate in the transfer of 1C units to various components involved in synthesis of purines, methionine → homocysteine, deoxythymidylate monophosphate (DNA)
401
folate deficiency impairs ___ and leads to___
DNA synthesis
| megaloblastosis
402
where do we get folate?
diet, no stores
| Green vegetables, fruits, liver
403
where is folate absorbed?
prox jejunum
404
3 major causes of folate deficiency
Decreased intake, inadequate diet, malabsorption
Increased requirement
Impaired use
405
what causes Decreased intake, inadequate diet, malabsorption folate def?
Chronic alcoholism, elderly, poor, sprue, lymphoma, drugs
406
what causes increased req of folate?
Pregnancy, infancy, malignancy
407
what causes impaired use of folate?
Folic acid antagonists inhibit dihydrofolate reductase in the recovery of tetrahydrofolate
408
what does hemolytic anemia include?
altered shape of the red cells as in hereditary spherocytosis
immune hemolytic anemia as may occur in Rh incompatibility
mechanical trauma to the red blood cells
409
aplastic anemia
Defect of the stem cell of the bone marrow
410
what causes Polycythemia Rubra Vera
mutation of JAK2
411
babesiosis
Endemic to cape cod
| Inclusions within RBC
412
2 main components of lymph node cortex
central germinal center surrounded by mantle zone
413
central germinal center of. lymph node
Composed of follicular cells
Represent various stages of B cell maturation
Follicular dendritic reticulum cells form the scaffolding for the germinal center and are antigen presenting cells for B cells
414
mantle zone of lymph node
composed of small round to slightly irregular lymphoid cells and represents an early stage of B cell activation
415
paracortex of lymph node
area between the secondary follicles
| composed primarily of small lymphocytes with admixed larger transformed lymphoid cells called immunoblasts
416
sinuses of lymph nodes
Vascular-like channels extending throughout the node lined by histiocytes
Act as filters to cleanse the lymph via the phagocytic activity of the lining histiocytes
417
medullary cords of lymph nodes
inner medulla of the lymph node is composed of predominantly plasma cells and extensions of the vascular sinusoids that contain histiocytes
418
where is the B cell area of the lymph node
secondary follicles
419
B cell associated antigens
CD19
CD20
CD10
420
where is the T cell area of the lymph node
paracortex
421
T cell associated antigens
```
CD2
CD3
CD4
CD5
CD7
CD8
```
422
non neoplastic lymph node disorders
Neutrophilia with reactive changes → increase neutrophils
| Infection
423
Neoplastic transformation of lymphoid cells results in ___
malignant lymphomas
424
non hodgkin's lymphoma
malignant lymphomas represent clonal expansions of discrete stages of differentiation of the cell as it progresses from a small round regular B cell to a plasma cell
425
A malignancy of the small round regular lymphocytes (circulating lymphocyte) gives rise to
malignant lymphoma, small lymphocytic type/chronic lymphocytic leukemia
426
A malignancy of germinal center cells (small and large cleaved, small and large non-cleaved) gives rise to
group of lymphomas collectively or known as follicular center cell lymphomas which may grow in a follicular (nodular) or diffuse growth pattern
427
A malignancy of germinal center small non-cleaved cells →
Burkitt's lymphoma
428
A malignancy of plasma cells →
multiple myeloma, plasmacytoma
429
Luke Collins B cell lymphomas
```
small lymphocytic
follicular center cell- small and large cleaved
small non cleaved (Burkitt's)
large non cleaved
immunoblastic sarcoma
```
430
Luke Collins T cell lymphomas
small lymphocyte
mycoses fungoides/sezary
immunoblastic sarcoma
431
are more lymphomas T or B cell type?
B cell (80%)
432
how to determine lineage of malignant lymphoma
Immunophenotypic studies
| Determination of lineage via detection of specific surface antigens
433
what is the most common lymphoma
follicular lymphoma
| tries to mimic B cell follicles
434
__ is neg in a normal lymph node but is pos in a lymphoma
Bcl-2
435
WHO classification
Sorts lymphoid neoplasms into 5 categories
436
Hodgkin lymphoma is a neoplasm of ___
Reed Sternberg cells
437
Hodgkin lymphoma
Lymphoid malignancy composed of distinctive large bi-nucleated cells called Reed-Sternberg (RS) cells associated with a characteristic mixed inflammatory background
438
classical RS cell histology
large, binucleated
Prominent eosinophilic centrally located nucleoli surrounded by a halo
Abundant eosinophilic/amphophilic cytoplasm
439
RS variant histology
mononuclear and multinucleated forms of RS cells
Lacunar cells
Popcorn cells
Malignant cell, but usually <5% of the population
440
Proportion of RS and RS variants present determines ___
the subclassification of Hodgkin’s lymphoma
441
Rye classifications
lymphocyte predominance
nodular sclerosis
mixed cellularity
lymphocyte depletion
442
Going from LP to LD there is an __ relationship between the proportion of lymphocytes present and the number of RS cells
inverse
443
4 major cell types in marrow
Erythroid → RBC
Myeloid → white blood cells
Megakaryocytes → platelets
Lymphocytes → B cells, T cells, plasma cells
444
leukemia
presence of circulating abnormal cells in blood
445
acute leukemia
circulating blasts of either myeloid origin (acute myelogenous leukemia) or lymphoid origin (acute lymphoblastic leukemia)
446
chronic leukemia
circulating mature cells of myeloid origin (chronic myelogenous leukemia) or lymphoid origin (chronic lymphocytic leukemia)
447
Acute Myelogenous Leukemia
Replacement of normal marrow elements by blasts
| >30% of the marrow cellularity
448
Myeloblasts in AML have:
large eccentrically placed nuclei
delicate nuclear chromatin
2-4 nucleoli and abundant cytoplasm which may or may not contain granules
myeloperoxidase positive
449
what surface antigens ID myeloid blasts in AML?
CD13
| CD33
450
Auer rods
abnormal granules
| diagnostic of AML
451
normal age range for AML
15-39
452
Clinical presentation of AML
```
Generally abrupt
Fatigue
Fever
infection
Easy bruising/bleeding
```
453
leukopenia
decrease in white cells
454
thrombocytopenia
decrease in platelets
455
AML prognosis
60% of patients achieve remission with chemotherapy but only 15-30% remain free of disease in 5 years
456
Acute Lymphoblastic Leukemia
Replacement of marrow by lymphoblasts of B or T cell origin
457
Lymphoblasts in ALL have
Predominantly round nuclei
Condensed chromatin
Single nucleoli
Scant agranular cytoplasm
458
most common form of ALL
pre-B cell type and primarily occur in childhood
459
how to distinguish btwn B and T cell ALL
immunophenotypic studies → flow cytometry
460
Presence and detection of the DNA polymerase → TdT (terminal deoxy-transferase) is very useful in the diagnoses of ___
ALL
461
when do cases of ALL peak
age 4
462
Infiltration of lymph nodes, spleen and liver is more common in ___
ALL than in AML
463
CNS involvement is more common in ALL than in AML
ALL than in AML
464
treatment of ALL
aggressive chemo cures 2/3 pts
465
Chronic Myelogenous Leukemia
Proliferation in the bone marrow of myeloid elements
466
who does CML primarily affect?
age 25-60
467
CML is associated with a specific chromosomal translocation
Involves the bcr gene on chr 9 and the abl gene on chr 22 → Philadelphia chromosome - PhP1P
468
clinical presentation CML
Mild to moderate anemia, fatigue, weight loss
| Dragging sensation in LUQ due to enlarged spleen
469
Majority of CML patients undergo ___ with evolution to acute leukemia
blast crisis
470
how many CML pts develop AML vs ALL?
~70% AML, 30% ALL
471
what drug treats CML?
gleevec
472
plasma cell neoplasms
Proliferation of a B-cell clone (plasma cells) that secrete a single homogeneous immunoglobulin or its fragments
473
multiple myeloma
Characterized by multiple tumorous masses scattered throughout the skeletal system
474
M component
Monoclonal immunoglobulin in the blood of multiple myeloma pts
aka monoclonal gammopathy
475
Bence Jones proteins
Free light chains of Igs are small enough to be excreted in the urine
476
Plasmacytoma
localized plasma cell tumors
477
what organ system is predominantly affected by multiple myeloma?
bone
478
multiple myeloma risk factors
men, people of African descent and older adults
479
how to diagnose multiple myeloma
Bone marrow electrophoresis
480
pathologic fracture
Multifocal destructive bone tumor composed of plasma cells → erode bone cortex
481
what bones are most affected in multiple myeloma
```
Bones in the axial skeleton
vertebra 66%
skull 41%
pelvis 28%
femur 24%
```
482
microscopic appearance of multiple myeloma
bone marrow reveals an increase in plasma cells (mature, immature, binucleated, multinucleated)
comprise greater than 30% of the cellularity
483
lab findings in multiple myeloma
Serum Ig > 3 gm/dL
M spike on SPEP
Bence Jones proteinuria may present as an isolated finding
normocytic/normochromic anemia, decreased WBC, decreased platelets
hypercalcemia due to increased bone resorption
rouleaux formation → high Ig causes red cells to stick to each other
484
clinical presentation of multiple myeloma
```
Confusion, weakness, lethargy due to hypercalcemia
Recurrent infections (Strep, Staph, E. coli) due to suppression of humoral immunity
Renal insufficiency (50% pts) due to the toxic effects of BJ proteins on renal tubular cells
Amyloidosis
```
485
Myelodysplastic syndromes
Disease often affects older patients who present with cytopenias involving varying lineages that are often refractory to treatment
486
Myelodysplastic syndromes eventually progress to __
AML
487
Disseminated intravascular coagulation
Activation of the coagulation cascade → microthrombus formation in the vasculature
488
causes of DIC
Sepsis
Malignancy
Major trauma
Obstetric complications
489
what can DIC cause
hemolytic anemia
| Can be fatal
490
Von Willebrand’s disease
bleeding disorder
| Characterized by bleeding from mucous membranes
491
most common from for VWf disease
type 1 → autosomal dominant
492
coagulation disorders
hemophilias
493
why is factor VIII replacement therapy no longer used?
Iatrogenic HIV from replacement from patients with HIV
494
Acute neuronal cell injury and neuronophagia
manifestations of acute, lethal injuries
495
Central chromatolysis
morphological manifestations of a reparative response to injury
496
Acute (hypoxic-ischemic) neuronal injury → ?
cell body shrinks, pyknosis, red neurons
497
red neurons
cytoplasms becomes hypereosinophilic
498
Neuronophagia
dying neuron is overrun by inflammatory cells
499
what remains after neuronophagia?
microglial nodule
500
where is central chromatolysis usually seen?
lower motor neurons
501
components of central chromatolysis
swelling of cell body, disappearance of Nissl bodies, displacement of nucleus to periphery
502
gliosis
proliferation of astrocytes upon brain tissue injury
503
Most common dementing disorder
AD
504
AD presentation
```
Memory failure
Especially short term
Deficiencies in abstract thinking, problem solving, visual-spatial orientation, mood regulation
Profound disabilities
Mute
Immobile
```
505
AD brain morpholgy
Diffuse symmetrical cerebral atrophy
Mainly in temporal, frontal, parietal lobes
Thinning of cortical ribbon
Prominent atrophy of medial temporal lobe structures
Mainly in hippocampus
506
microscopic features of AD
neurofibrillary tangles
senile plaques
amyloid angiopathy (sometimes)
507
neurofibrillary tangles
intracellular inclusions containing abnormally phosphorylated tau protein
508
where are NFTs found
neuropil threads
| dystrophic neurites
509
senile plaques
extracellular deposits of beta amyloid
510
amyloid angiopathy
deposits of Aβ in vascular walls of meningeal and parenchymal vessels
511
how to visualize amyloid angiopathy
Congo red
512
how is amyloidogenic Aβ generated
If APP is not cleaved by a-secretase
513
what does Cleavage by β-secretase and g-secretase cuase
Aβ which promotes inflammation that can alter tau phosphorylation and induce neuronal oxidative injury
514
where is APP located
chr21
515
familial AD
point mutations in APP
| develops in 20s/30s
516
what do mutations in presenilins cause?
gain of function of g-secretase → generates increased amounts of Aβ
517
sporadic AD is more likely in patients with
individuals of a particular allele (e4) of ApoE gene
| This isoform promotes Aβ generation and deposition
518
what is the mutation in frontotemporal dementias, not AD
Mutations in gene encoding tau (MAPT)
519
clinical presentation of frontotemporal dementias
progressive deterioration in language and changes in personality
520
morphology of frontotemporal dementias
Atrophy of frontal and temporal lobes
| Degree and combo affects presentation
521
subtypes of frontotemporal dementias
Pick disease
Corticobasal degeneration
Progressive supranuclear palsy
522
Molecular genetics and pathogenesis of frontotemporal dementias
Some families with FTD have mutations in tau-encoding MPTP gene → tau forms with 4 or 3 MAP binding regions (4R or 3R tau)
523
how to tell difference btwn AD and frontotemporal dementias?
neuropathological diagnosis
524
what clinically characterizes PD?
Rigidity
Bradykinesia
resting tremor
525
what are clinical manifestations of PD due to?
decreased dopaminergic input to the striatum because of degeneration of dopaminergic neurons of the substantia nigra
526
Clinical hallmark on gross exam of PD
pallor of substantia nigra
527
microscopic appearance of PD
Loss of pigmented (dopaminergic) neurons
Gliosis in substantia nigra
Presence of Lewy bodies
528
Lewy bodies
intraneuronal inclusions that contain primarily alpha-synuclein (protein associated with synaptic transmission)
assoc with PD
529
Parkinsonism
```
clinical syndrome characterized by:
Decreased facial expression
Stooped posture
Slowness of movement
Rigidity
“Pill-rolling” tremor
```
530
what causes the symptoms of parkinsonism
damage to nigrostriatal dopaminergic system or blockade of postsynaptic R
531
a-synuclein
lipid binding protein associated with synapses
| 1st gene to be identified as a cause of autosomal dominant PD encodes
532
Mutations in ___ are more common causes of autosomal dominant PD
LRRK2
533
parkin
E3 ubiquitin ligase
534
Juvenile autosomal recessive PD is caused by a loss of function mutation in the gene encoding __
parkin
535
DJ-1
protein involved in regulating redox response to stress
| involved in autosomal recessive PD
536
PINK-1
kinase important for mitochondrial function
| kinase important for mitochondrial function
537
what causes HD
mutation in gene that codes for huntingtin protein
538
what sequence is important in huntingtin
CAG repeat
| abnormally long in HD pts
539
when doe HD start
middle/late life
540
symptoms of HD
Chorea
| Cognitive and affective disorders
541
gross exam of HD brain
striatal atrophy of caudate nucleus
| Frontal atrophy in later stages
542
microscopic exam of HD brain
neuronal loss and astrogliosis
543
ALS
Neurodegenerative disorder affecting upper and lower motor neurons
544
symptoms of ALS
Severe muscle atrophy
| Hyperreflexia
545
why does severe muscle atrophy occur in ALS
Due to anterior horn loss
546
why does hyperreflexia occur in ALS
Due to degeneration of corticospinal tracts
547
fasciculations
Involuntary contractions of individual motor units
| symptom of ALS
548
__% patients have an autosomal dominant inherited form of ALS
10
| *starts 10 years earlier than sporadic
549
ALS gross exam
```
atrophy of anterior motor nerve roots of the spinal cord
Precentral gyrus (motor cortex) may be atrophic
```
550
ALS microscopic exam
loss of anterior horn cells (motor neurons) and astrocytosis in the spinal cord
Loss of motor neurons in brainstem and motor cortex
Degeneration of corticospinal tracts
Skeletal muscle shows denervation atrophy
551
what mutation causes most familial ALS cases?
Mutation in SOD1 on chr21
552
SOD1 role
removes superoxide radicals
553
clinical presentation of MS
```
Hyperreflexia
Weakness
Spasticity
Dysarthria
Tremor
Ataxia
Extraocular muscles and vision disturbances
Spontaneous exacerbations and remissions
```
554
why does MS have distinct episodes of neurologic deficits separated in time
white matter lesions
555
microscopic MS appearance
Active plaques of demyelination show ongoing myelin breakdown
Abundant macrophages containing lipid rich debris
Lymphocytes are found around vessels
556
appearance of inactive MS plaque
thinning of axons and prominent astrogliosis
| Macrophages are mostly gone
557
common location of MS plaques
periventricular area
558
symptoms of CTE
```
Deterioration in attention, concentration, memory
Disorientation
Confusion
Dizziness
Headache
Later, dementia
```
559
distinct abnormalties in. what in CTE?
phosphorylated tau
560
why is CTE unique?
represents progressive tauopathy with obvious environmental etiology
561
Neurofibrillary degeneration in CTE characterized by
Preferential involvement of superficial layers of frontal and temporal cortices with patchy distribution and propensity for sulcal depth
Tau-immunoreactive NFTs, neuropil threads, astrocytic tangles
Prominent perivascular involvement
562
cerebral infarct
An area of CNS tissue necrosis localized to a particular territory of vascular supply
All cellular elements are rendered non-viable by hypoxia/ischemia
563
stroke
clinical term for syndrome of rapidly evolving or sudden-onset, non-epileptic neurologic deficit that lasts for >24 hrs
564
venous infarction
tissue ischemia is due to occlusion of a large vein and consequent stasis
565
what is most sensitive to neuronal ischemia
protein synthesis
566
when is protein synthesis suppressed?
0.40 ml/g/min
567
what happens to glc use when there is neuronal ischemia
Glucose utilization transiently increases at a flow rate below 0.35 before sharp decline to 0.25
568
anoxic depolarization
rise in extracellular K+ below 0.15 and parallel influx of Ca++ → demise of membrane potential and structural integrity
569
presentation of brain hemorrhage
```
Sudden headache
Onset of neurologic deficit
Edema
Increased intracranial pressure
Herniation
Bloody CSF
```
570
common causes of brain hemorrhage
```
Hypertension
Cerebral amyloid angiopathy
Anticoagulant administration
Primary or secondary brain neoplasm
Arteriovenous malformations
Aneurysms
Recreational drug use
```
571
Hypertensive intraparenchymal hemorrhage
Results from rupture of parenchymal arterioles that have become less compliant and weakened due to replacement of smooth muscle by fibrocollagenous tissue
Usually attributed to arteriosclerosis due to chronic hypertension
572
what characterizes Hypertensive intraparenchymal hemorrhage
```
Intimal hyperplasia
Elastic tissue reduplication
Presence of foamy macrophages in arterial wall
Thickening of media
Adventitial fibrosis
```
573
where do SAH usualyl occur
Commonly develops from rupture of aneurysm in the circle of Willis
574
berry aneurysms
most common cause of non traumatic SAH
Certain segments of smooth muscle media prone to develop aneurysms
Associated with hypertension and atherosclerosis
575
concussion
no structural damage, brief impairment of consciousness
576
contusion
bruise of brain parenchyma
577
skull fracture
no consequences or accompanied by brain contusion, CSF leak due to meningeal tear, or epidural hematoma due to vascular tear
578
how does an epidural hemorrhage happen?
Results from a skull fracture → tearing of middle meningeal artery
579
what does epidural hemorrhage affect in adults?
temporal fossa
580
what does epidural hemorrhage affect in children?
posterior fossa
581
clinical presentation of epidural hemorrhage
Momentary loss of consciousness
Followed by asymptomatic period
1-48 hours
Followed by symptoms of elevated intracranial pressure
Without surgical intervention → herniation of medial temporal lobe, coma, death
582
acute SDH results from?
Rapid acceleration or deceleration → brain inertia, traction/tearing of bridging veins between brain and dura occurs
583
chronic SDH
Rupture of bridging veins → cycles of organization and re-bleeding due to formation of densely vascular granulation tissue tend to bleed spontaneously and perpetuate pathologic process
584
most common sites of metastatic tumors
```
Lung
Breast
Skin → melanoma
Kidney
GI
```
585
how do tumors spread to the. brain?
Spread to brain is mainly by hematogenus dissemination
586
Meningeal carcinomatosis
tumor nodules studding surface of brain, spinal cord, intradural nerve roots
587
what is meningeal carcinomatosis associated with?
small cell carcinoma and adenocarcinoma of lung
| Carcinoma of breast
588
Primary tumors arise from _____
cells that are intrinsic to the CNS
| Including calvarium and tumors of neuroepithelial origin and non-neuroepithelial origin
589
where do gliomas occur?
throughout CNS
590
what are low grade gliomas more likely to how?
phenotypic markers of mature cells
591
microscopic appearance of high grade gliomas
mitoses, microvascular proliferation, necrosis
592
WHO grade diffuse astrocytomas
II
593
what age is affected by diffuse astrocytomas
30-40
594
macroscopic appaerance of diffuse astrocytomas
tumors enlarge and distort involved brain structures
| Often blur normal anatomic landmarks
595
microscopic appaerance of diffuse astrocytomas
moderately cellular tumors composed of well-differentiated astrocytes
596
diffuse astrocytomas are __% of adult primary brain tumors
80
597
WHO grade anaplastic astrocytomas
III
598
where do anaplastic astrocytomas occur
Arise in setting of preexisting low-grade diffuse astrocytoma
Can also present de novo
599
microscopic appearance of anaplastic astrocytomas
tumors are more cellular and pleomorphic than grade II tumors
Contain mitoses or vascular proliferation
600
glioblastoma WHO grade
IV
601
what age do glioblastomas peak
45-70
602
radiologic/macroscopic presentation of gliomas
butterfly pattern caused by spread of tumor across the corpus callosum into opposite hemisphere
603
microscopic presentation of gliomas
high cellularity, marked pleomorphism, mitoses, microvascular proliferation, pseudopalisading necrosis
604
oligodendroglioma WHO grade
II
605
oligodendroglioma peak ages
30-60
606
oligodendroglioma
Diffusely infiltrating glioma composed of cells morphologically resembling oligodendrocytes
Relatively benign, slowing growing
607
oligodendroglioma presentation
Patients may often present with a long history or neurological symptoms
Often chronic seizure
608
Anaplastic Oligodendroglioma WHO grade
III
609
Anaplastic Oligodendroglioma microscopic appearance
histological appearance of oligodendroglioma with focal or diffuse features of overt malignancy
Increased cellularity
Cytologic atypia
Frequent mitoses
Sometimes microvascular proliferation and necrosis
610
where do ependymoma arise?
next to ependymal-lined ventricular system
611
where do ependymomas occur in <20yr
near 4th ventricle
612
where do ependymomas occur in adults
spinal cord
613
why are ependymomas difficult to remove
Difficult to remove because of proximity to vital pontine and medullary nuclei
614
microscopic appearance of ependymoma
perivascular pseudorosettes
615
anaplastic ependymoma WHO grade
III
616
microscopic appearance of anaplastic ependymoma
cellular pleomorphism, necrosis, mitoses, vascular proliferation
617
Gangliocytomas WHO grade
I
618
what do gangliocytomas consist of?
Consist entirely of mature readily recognized ganglion cells (mature neurons)
Mitoses and necrosis are absent
619
gangliogliomas
Mix of mature appearing neurons and glial cells
| Glial component can become anaplastic
620
medulloblastoma WHO grade
IV
621
where do medulloblastoma arise
cerebellum
| Usually in vermis
622
what can medulloblastomas cause
Ataxia
Headache
Vomiting
Obstruction of 4th ventricle with hydrocephalus
623
medulloblastoma histology
small blue cell tumors with mitoses, necrosis, apoptosis
624
meningiomas
Benign, slow growing tumors of adults
| Usually attached to dura
625
what do meningiomas arise from?
meningothelial cells of arachnoid
626
common sites of meningiomas
```
Parasagittal aspect of brain convexity
Dura over the lateral convexity
Wing of sphenoid
Olfactory groove
Sella turcica
Foramen magnum
```
627
schwannoma WHO grade
I
628
what CN do schwannomas arise on?
vestibular branch of CN XIII → acoustic neuroma
629
where do schwannomas arise in spinal nerve roots?
sensory nerve roots in the lumbosacral region
630
neurofibroma WHO grade
I
631
what are neurofibromas composed of?
fibroblasts and pericytes mixed with Schwann cells and scattered mast cells
632
Cutaneous neurofibromas
nodular lesion in the skin
633
peripheral single nerve neurofibroma
solitary neurofibroma
634
peripheral major nerve trunk neurofibroma
plexiform neurofibromas
635
Malignant peripheral nerve sheath tumors
Highly malignant sarcomas → WHO grade IV
| De novo or from transformation of plexiform neurofibromas
636
Neurofibromatosis type 1 symptoms
multiple neurofibromas
gliomas of the optic nerve
LIsch nodules
cafe au lait spots
637
lisch nodules
pigmented nodules of iris
638
cafe au lait spots
cutaneous hyperpigmented macules
639
Neurofibromatosis type 1 frequency
1/3000
640
NF1 gene and product
tumor suppressor gene
| neurofibromin
641
neoplasms associated with neurofibromatosis type 1
MPNSTs, rhabdomyosarcomas, pheochromocytomas, carcinoid tumors
642
Neurofibromatosis type 2
Develop a range of tumors
Commonly bilateral VIII nerve schwannomas and multiple meningiomas
Gliomas occur in the spinal cord
643
Neurofibromatosis type 2 frequency
1/40,000
644
NF2 gene product
merlin
645
NF2 associated neoplasms
Bilateral schwannomas, neurofibromas, ependymomas, other gliomas, multiple meningiomas
646
meningitis
inflammatino of meninges
647
encephalitis
inflammation of brain
648
Route of entry of microorganisms into CNS
hematogenous spread
Retrograde spread through venous system is possible
Direct implantation can follow traumatic injury or following surgery
Extensions of local infections, such as a tooth
Spread from peripheral nerves
649
Acute pyogenic meningitis cause in elderly
Streptococcus pneumoniae, Listeria monocytogenes
650
Acute pyogenic meningitis cause in young adults
Neisseria meningitides
651
Acute pyogenic meningitis cause in young adults
E. coli, B streptococci
652
classic presentation of acute pyogenic meningitis
Stiffness in neck due to irritation of meninges
653
gross exam of acute pyogenic meningitis
diffuse swelling of brain with focal collections of pus beneath meninges → clouding and opacification
Pus
654
complications of acute pyogenic meningitis
Swelling → compromise of blood flow→ cerebral infarction
Herniation
Compromise of respiratory centers or cranial nerve impingement
Long term → fibrosis of meninges can occur with development of chronic adhesions
655
Aspergillosis
2nd most common fungal infection of CNS encountered at autopsy
Cause → inhalation of airborne spores with hematogenous dissemination to the brain
656
Mucormycosis
regional brain infection due to spread from nose or sinuses, or from systemic disease with hematogenous dissemination in immunocompromised hosts
657
myocytic infections
aspergillosis
| mucormycosis
658
what can myocytic infections lead to?
invade blood vessels growing directly through the wall
| Can lead to thrombosis and subsequent brain infarction and necrosis
659
Toxoplasma gondii
intracellular protozoan parasite of domestic cats
660
Acquired toxoplasmosis
Acquired through contamination with feces from infected cats
Neurologic impairment can be localized or diffuse
Fatal in immunocompromised patients
661
what characterizes acquired toxoplasmosis
necrosis
Encapsulated form of trophozoites → bradyzoites are found near necrosis
Abscess formation
662
symptoms of congeintal toxoplasmosis
Infant convulsions
Chorioretinitis
Hydrocephalus
663
pathology of congeintal toxoplasmosis
areas of parenchymal necrosis and calcifications
664
symptoms of CNS viral infections
Meningoencephalitis with similar features regardless of specific agent
Brain is edematous with petechial hemorrhages and necrosis
665
microscopic symptoms of CNS viral infections
perivascular lymphocytic infiltrate
666
RNA viruses
```
enteroviruses
paramyxoviruses
rubella
rabies
arboviruses
```
667
Progressive rubella panencephalitis
rare and delayed complication of childhood or congenital rubella infection
668
Congenital rubella syndrome
low birth weight, cardiac defects, cataract, chorioretinitis, neurologic defects
669
Rabies
Acute neurologic disease develops after incubation and prodrome
Virus replicates in muscle and is transported by axons to the CNS
670
how to diagnose rabies
Diagnosed by identification of Negri bodies in neuronal cytoplasm
671
arboviruses
Cause encephalitis
Usually have animal or mosquito vectors
Example: West Nile, Western equine encephalitis (infants), Eastern equine encephalitis (children and elderly), St. Louis, La Crosse
672
gross pathology of arboviruses
generalized edema and focal petechial small hemorrhages in the gray and white matter
673
CNS DNA viruses
HSV
varicella-zoster
cytomegalovirus
674
how does HSV-1 work
travels by retrograde axonal transport along sensory fibers to the trigeminal ganglion where latency is established
675
how does HSV-2 work
established latency in the sacral dorsal root ganglion
| Can infect brain of fetus passing through the canal
676
how does varicella zoster affect CNS
Virus post infectious encephalitis due to latent infection in dorsal root or trigeminal ganglia
After retrograde axonal transport of virus from periphery
677
cytomegalovirus
Typically in fetuses and immunocompromised patients
Most common intrauterine viral infection with residual lesion in survivors of acute neonatal illness
Intranuclear viral inclusions within large cells
678
microscopic path of prion disease
spongiform change
Neuronal death
Synaptic loss
679
spongiform change
microvascular bubbles within neuropil
680
CJD
prion disease
Typically begins with subtle motor signs
Followed by severe cerebellar ataxia and global dementia in under a year
Death within 3 years
681
kuru
```
prion disease
Found among tribes of Papua New Guinea
Decreased since cannibalism has declined
Motor signs
Characteristic amyloid plaques in cerebellar cortex
```
