Pathology 2 Flashcards
1
Q
Functional unit of ovary
A
Follicle
2
Q
3 types of cells in the ovary
A
Oocyte, Granulosa, Theca
3
Q
Which hormone stimulates the theca cells?
A
LH; androgen
4
Q
Which hormone stimulates the granulosa cells?
A
FSH; converts androgen to estradiol
5
Q
The 2 phases of the endometrial cycle
A
- Proliferative
2. Secretory
6
Q
The corpus luteum primarily secretes
A
Progesterone
7
Q
Bleeding into the corpus luteum
A
Hemorrhagic luteal cyst
8
Q
Degeneration of ovarian follicles leads to…
A
Follicular cysts
9
Q
Multiple follicular cysts in ovary due to hormone imbalance. Which hormone is increased the most?
A
PCOD; LH:FSH >2
10
Q
In response to LH, theca cells produce
A
Androgen
11
Q
Describe hirsuitism and obesity seen in PCOD.
A
Hirsuitism, estrone (peripheral conversion of androgen leads to obesity), negative FSH feedback b/c of high estrone and hence the follicle degenerates
12
Q
Obese woman with infertility, oligomenorrhea, hirsuitism, insulin resistance (DM2), high risk of endometrial ca
A
PCOD
13
Q
3 major categories of ovarian tumors
A
- Germ cell (oocyte)
- Sex cord stromal (G,T)
- Surface epithelial
14
Q
Most common type of ovarian tumor
A
Surface epithelial
15
Q
Surface epithelial tumors of the ovary are typically derived from…
A
Coelomic epithelium that lines the ovary
16
Q
Single cystic ovarian mass with simple, flat lining arising in a pre-menopausal woman
A
Benign cyst adenoma
17
Q
What is the name for tumors in between benign and malignant ovarian tumors?
A
Borderline
18
Q
BRCA1 mutation carriers most classically p/w what subtype of ovarian carcinoma?
A
Serous cyst AC (ovary & fallopian tube)
19
Q
Malignant ovarian ca assoc w/ endometriosis. Any other cancer to look for??
A
Endometrioid tumor (of ovary & endometrium!)
20
Q
Malignant ovarian ca that contains urothelium.
A
Brenner tumor
21
Q
T/F Surface epithelial tumors generally present late.
A
True
22
Q
Useful serum marker for ovarian ca treatment/recurrence
A
CA-125
23
Q
Germ cell tumors of the ovary typically present in women of what age?
A
Reproductive age
24
Q
5 different types of ovarian germ cell tumors
A
- Teratoma (fetal)
- Embryonal
- Yolk sac
- Germ cell (dysgerminoma)
- Placental (choriocarcinoma)
25
Cystic ovarian tumor composed of fetal tissue derived from 2-3 embryologic layers
Cystic teratoma [B/L in 10% of patients]
26
Most common type of immature tissue in an immature teratoma
Neuroectoderm
27
The most common type of somatic malignancy that arises from a malignant teratoma
Squamous cell carcinoma of the skin
28
Cystic teratoma composed primarily of thyroid tissue
Struma ovarii
29
Ovarin tumor: large cells with clear cytoplasm and central nuclei; testicular counterpart is called __________. What is the serum tumor marker?
Dysgerminoma; Seminoma
| Serum tumor marker LDH
30
Malignant tumor that mimics the yolk sac; most common germ cell tumor in children. Serum AFP is elevated. What tumor and what is seen on histology?
Endodermal sinus tumor
| * Schiller-Duval bodies on histology (glomerulus-like structure)
31
Malignant-like proliferation of placenta-like tissue. Composed of trophoblasts and synctiotrophoblasts without villi.
Choriocarcinoma: small, hemorrhagic tumor with early hematogenous spread. High b-HCG; poor response to CTX
32
Response to CTX: gestational chorioca vs. germ cell chorioca
Gestational with very + response
33
Ovarian germ cell tumor with large, primitive cells; aggressive with early mets
Embryonal ca
34
Sex-cord stromal neoplasm of ovary that often produces estrogen [p/w estrogen excess]
Granulosa-theca cell tumor
35
Sex-cord stromal tumor of ovary that can produce androgen: hirsutism or virilization. What is the characteristic histology?
Sertoli-Leydig cell tumor: Reinke crystals [pink cells with crystals]
36
Sex-cord stromal tumor of ovary with fibroblasts. What is the KEY association?
* Fibroma.
| - - Pleural effusion and ascites: Meigs syndrome
37
Kruckenberg tumor
From the *stomach* (diffuse -- signet ring), breast (lobular), colon ca
38
Mucinous tumor of ovary vs. Kruckenberg
Mucinous: unilateral
Kruckenberg: B/L
39
Pseudomyxoma peritonei tumor is primarliy from
Appendix with ovarian mets
40
Implantation of fertilized ovum at site other than uterine wall; key risk factor
Scarring; endometriosis
| * Common site: mpulla lumen
41
Spontaneous abortion presents at what week or before? Classic causes include...
20 weeks
| * Chromosomal anomalies, hypercoaguable states (SLE), congenital infection, teratogens
42
Teratogens can lead to:
Until week 2:
Weeks 3-8:
After week 8:
Until week 2: spontaneous abortion
Weeks 3-8: malformation
After week 8: hypoplasia
43
Implantation of placenta in lower uterine segment (overlies cervical os)
Placenta previa
44
Separation of placenta from decidua prior to deliver; p/w 3rd trimester bleeding and fetal insufficiency
Placental abrutption
| * Still birth
45
Placenta previa vs. abruption vs. accreta
Previa: Internal os
Abruption: Separation
Accreta: Myometrium
46
Improper implantation of placenta into the myometrium with little or no intervening decidua. p/w difficult delivery of the placenta and post-partum bleeding. Requires hysterectomy
Placenta accreta
47
What is the decidua?
Endometrium under the influence of progesterone
48
Pregnancy induced HTN, proteinuria and edema. Underlying pathophysiology
Pre-eclampsia; 2/2 abnormality of MF vascular interface in placenta [GEPH]
49
Pregnancy induced HTN, proteinuria and edema & seizures.
Eclampsia
50
What is the classic histologic finding in a pregnant woman with pregnancy induced HTN, proteinuria and edema.
Fibrinoid necrosis of placental vessels
51
Pregnancy induced thrombotic microangiopathy associated with pre-eclampsia
*HELLP*
| Hemolysis, elevated liver enzymes, low platelets
52
Risk factors for SIDS (1 month-1 year)
Stomach, *smoking in households*, prematurity
53
Abnormal conception characterized by swollen and edematous villi with proliferation of trophoblasts
Hydatidiform mole; uterus expands faster than normal / b-HCG higher than expected
54
Passing of grape-like masses through vaginal canal in 2nd trimester
Hydatidiform mole
55
Snow-storm appearance on U/S with absent fetal heart sounds
Hydatidiform mole
56
Partial vs. Complete mole
* Genetics
* Fetal tissue
* Villous edema
* Trophoblastic proliferation
* Risk for chorica
Complete
* Genetics: all from dad 46
* Fetal tissue: absent
* Villous edema: all!
* Trophoblastic proliferation: complete!!
* Risk for chorica: high risk!
57
What cells make beta-HCG?
Synciotrophoblasts
58
What is monitored to ensure adequate hydatidiform mole removal?
Beta-HCG
59
The key complication to screen for following a choriocarcinoma
Gestational choriocarcinoma
60
Do you see villi in a choriocarcinoma?
No
61
Secondary amenorrhea 2/2 loss of basalis of endometrium and subsequent scarring. What is the syndrome and what is the cause?
Syndrome: Asherman
Cause: Overaggressive D & C
62
Lack of ovulation; results in estrogen-driven proliferative phase w/o progesterone-driven secretory phase; common cause of dysfunctional uterine bleeding during menarche and menopause
Anovulatory cycle
63
Common cause of acute endometritis
Retain products of conception
64
Characteristic cell seen in chronic endometritis
**Plasma cell**
| Arises 2/2 retained products, PID, IUD, TB
65
Hyperplastic protrusion of endometrium that p/w abnormal uterine bleeding. What is the high yield cause?
Endometrial polyp 2/2 AE of Tamoxifen
66
Endometrial glands AND stroma outside the endometrial lining p/w dysmenorrhea and pelvic pain
Endometriosis
67
3 theories of endometriosis
1. Retrograde menstruation
2. Metaplastic (Mullerian duct derivatives)
3. Lymphatic dissemination (can see in lung!)
68
```
Common sites of involvement of endometriosis:
**Ovary
Uterine ligaments
Pouch of Douglas
Bladder wall
Bowel serosa (gunpowder lesions)
Fallopian tube mucosa
```
```
Ovary: chocolate cyst
Uterine ligaments: pelvic pain
Pouch of Douglas: defacation
Bladder wall: urination
Bowel serosa: Abdominal pain/adhesions
Fallopian tube mucosa: scarring
```
69
Endometriosis in the myometrium is called
Adenomyosis
70
Does endometriosis increase risk of ovarian cancer?
Yes
71
Hyperplasia of endometrial glands relative to stroma is driven by:
Endometrial hyperplasia: ESTROGEN
| - P/W post-menopausal uterine bleeding
72
Most important predictor for progression to carcinoma in endometrial hyperplasia
Cellular atypia
73
2 pathways of endometrial carcinoma. What is the classical histology of each?
1. Hyperplasia: fat, young
* Endometrioid sub-type
2. Sproadic: skinny, old
* Atrophic [serous/papillary histology -- psammoma bodies]
74
The sporadic pathway of endometrial cancer is driven by what mutation?
p53 mutations
75
Can sporadic endometrial cancer lead to psammoma body formation?
Yes
76
Psammoma body formation (4) cancers
1. Papillary ca thyroid
2. Meningioma
3. Papillary serous ca ovary
4. Mesothelioma
77
Benign proliferation of smooth muscle arising from myometrium in pre-menopausal women who p/w multiple, well-defined white whorly masses
Leiomyoma
78
Most common symptom of leiomyoma
Asymptomatic (can cause abnormal UB, infertility, pelvic mass)
79
Malignant proliferation of smooth muscle arising from myometrium; arises de novo in a post-menopausal woman; single lesion with nex/hemorrhage
Leiomyosarcoma
80
The neck of the uterus is called
The cervix
81
Endocervix, Exocervix epithelium; transformation zone
Endo: columnar
Exo: squamous
82
E6, E7 of high risk HPV
p53, Rb
83
T/F Phosphorylated Rb releases E2F
True
84
T/F Hyperphosphorylated Rb leads to unregulated cell growth
True
85
Secondary risk factors for cervical cancer (besides HPV)
Smoking, immunodeficiency
86
2 important cancers that can be caused by smoking [non-classically]
1. Cervical
| 2. Pancreatic
87
Can HPV cause cervical AC?
Yes [not picked up by pap smear]
88
T/F Cervical ca can often p/w hydronephrosis
T
89
One of the most common causes of death in cervical ca
Renal failure 2/2 hydronephrosis
90
Abnormal pap smear is followed by...
Colposcopy and bx
91
2 major limitations of pap smear
1. Not at transformation zone [false negative]
| 2. Does not detect AC
92
Quadrivalent HPV immunization covers against
HPV 6, 11, 16, 18
93
Focal persistence of columnar epithelium in the upper vagina is called ____________. What is the major risk factor?
1. Vaginal adenosis
| 2. DES exposure in utero
94
Vaginal derivatives
Upper 2/3
Lower 1/3
Upper 2/3: Mullerian duct [cervix, uterus]
| Lower 1/3: UG sinus
95
During development, the Mullerian duct's epithelium (name it) is replaced by (name it)
Originally: columnar
| Replaced by: st. squamous
96
Rare complication of DES-associated vaginal adenosis
Clear cell adenocarcinoma
97
Key complications DES daughters & mom's
Daughters:
1. Clear cell AC
2. Pregnancy/gestational [smooth muscle problems]
Mom's: BRCA
98
Malignant mesenchymal proliferation of immature skeletal muscle p/w bleeding & grape-like mass protruding from vagina or penis of child < 5 yo
Embryonal rhabdomyosarcoma (Sarcoma boytrides)
99
Embryonal rhabdomyosarcoma histology and IHC
- Rhabdomyoblast with cytoplasmic cross-striations
| - Positive IHC for desmin and myogenin
100
Cancer from lower 1/3 of vagina goes to what LN
Inguinal nodes [UG sinus]
101
Cancer from upper 2/3 of vagina goes to what LN
Iliac nodes [Mullerian duct]
102
Cystic dilation of Bartholin gland usually unilateral and in the lower portion of the vaginal vestibule
Bartholin cyst 2/2 inflammation in a woman of repro age
103
Warty neoplasm 2/2 HPV 6, 11 characterized by koilocytic change
Condyloma accuminatum
104
How is HPV classfied into high and low risk?
DNA sequencing [6, 11 vs. 16,18, 31, 33]
105
Thinning of epidermis and fibrosis of dermis; leukoplakia with parchmant-like vulvar skin in post-menopausal .
Lichen sclerosis
106
Lichen sclerosis: any increased risk of squamous cell carcinoma?
Yes: slightly increased risk
107
Hyperplasia of vulvar squamous epithelium; leukoplakia with thick, leathery vulvar skin associated with chronic irritation/scratching
Lichen simplex chronicus
108
Lichen sclerosis vs. Lichen simplex chronicus
Sclerosis: thinning-parchmant, inc. risk
Simplex: thickening-leather, no inc. risk
109
Does vulvar carcnioma p/w leukoplakia?
Yes
110
What are the 2 pathways of vulvar carcinoma? What are the risk factors for each?
1. HPV
2. Non-HPV
* Long-standing lichen sclerosis
111
**Malignant epithelial cell in epidermis** of the vulva that p/w erythematous, pruritic, ulcerated skin that represents carcinoma in situ, but not necessarily underlying cancer
Extra-mammary Paget Disease
112
What is the DDX of extra-mammary Paget disease? What IHC stains can help you tell the difference?
Melanoma: PAS-, keratin-, S100+
Carcinoma: PAS+, keratin+, S100-
113
Goal of primary hemostasis & secondary hemostasis
Platelet plug; stabilize the plug
114
The step just prior to primary hemostasis is mediated by
Transient vasoconstriction [neural stimulation & endothelin]
115
VWF binds to
Sub-endothelial collagen & gp1b (adhesion)
116
VWF comes from
Platelet itself & endothelilal cells [Weibel Paliade body]
117
Weibel Paliade body contains
1. P-selectin
| 2. VWF
118
2 mediators released by de-granulated platelets
1. ADP (dense core granules) that promotes gp2b/3a expression
2. TXA2 (COX)
119
ADP induces platelets to express
Gp2B/3a for platelet aggregation
120
Platelets link to one another through what molecule?
Fibrinogen
121
Four steps of primary hemostasis
1. Vasoconstriction
2. Adhesion
3. Degranulation
4. Aggregation
122
A pt w a disorder of primary hemostasis p/w
Mucosal (nose, cough, GI, hematura, menstrual) and skin bleeding [petechiae, purpura, eccymoses > 1 cm]; easy bruising
123
Severe thrombocytopenia can result in this worrisome complication
Intracranial bleeding
124
Do patients with qualitative disorders of platelets get petechiae?
No; only quantitative
125
What are the useful laboratory studies in a patient with bleeding?
Platelet count, bleeding time, blood smear, bone marrow bx
126
Autoimmune production of IgG against platelet antigens [most common cause of thrombocytopenia in children and adults]
ITP [Ab-bound platelets are consumed by splenic macrophages resulting in thrombocytopenia]
127
ITP in childrens vs. adults
Children: acute 2/2 viral infection/immunization and self-limiting
Adults: women of child-bearing ages; primary or secondary [SLE]; may cause tbopenia in offspring (IgG)
128
One of the most important secondary causes of ITP in adults
SLE
129
Lab findings in ITP
Low platelets; normal PT/PTT; increased megakaryocytes on BM bx
130
3 treatment of ITP (3)
* CS: initial
* IVIG (splenic macrophages start to eat the IVIG to distract them)
* Splenectomy: eliminate source of Ab and site of destruction
131
Pathologic formation of platelet microthrombi in small vessels
Microangiopathic hemolytic anemia (Schistocytes); platelets are consumed
132
Any difference between a schistocyte and a helmet cell?
No
133
2 disorders (really one) in which microangiopathic hemolytic anemia is seen
TTP & HUS
134
Why are platelet thrombi formed in TTP?
Decrease in ADAMSTS13 enzyme: inability to de-polymerize & degrade VWF
135
Decreased ADAMSTS13 is usually due to
1. Acquired Auto-Ab
| 2. Genetics
136
HUS is due to
Endothelial damage by drugs or infection
* E. coli 0157:H7 [verotoxin] in kidney and brain [exposure to undercooked beef w/ mucusy diarrhea]; also damages ADAMSTS13
137
Skin and mucosal bleeding, microangiopathic hemolytic anemia, fever, renal insufficiency, and CNS abnormalities
TTP/HUS
TTP: neurological
HUS: renal
138
Lab finding differences between ITP & TTP/HUS
Same; TBOpenia, normal coag, anemia with schistocytes, megakaryocytes on BM bx
139
Treatment of TTP
Plasmapheresis and CS
140
gp1b deficiency & impaired platelet adhesion
Bernard-Soulier
| * Mild thrombocytopenia with enlarged platelets
141
Genetic defect of gp2b/3a [platelet aggregation]
Thrombasthenia of Glanzmann & Nagelli
142
Genetic defects of platelet adhesion and aggregation
Adhesion: Bernard Soulier
Aggregation: Thrombasthenia of Glanzman Nagelli
143
ASA irreversibly inactivates
COX; lack of TXA2 impairs platelet aggregation
144
T/F Uremia disrupts platelet function
True: adhesion & aggregation
145
Activation of coagulation factors requires:
1. Exposure to activating substance
2. Phospholipid surface [platelet surface]
3. Calcium
146
Clinical features of 2ndary hemostasis disorders
Deep bleeding into muscles and joints; re-bleeding 2/2 surgical procedures
147
PT vs. PTT
PT: extrinsic
PTT: intrinsic
148
Name the factors in both the intrinsic and extrinsic coagulation cascades
12, 11, 9, 8 vs. 7 [10, 5, 2, 1]
149
What activates factor 12?
Sub-endothelial collagen [SEC]
150
What activates factor 7?
Tissue thromboplastin
151
Heparin monitored with
PTT
152
Warfarin monitored with
PT
153
Genetic XLR of Factor 8
| T/F Can arise from a new mutation without any family hx
Hemophilia A
| * True
154
Most common coagulation factor inhibitor
Anti-Factor 8
155
Mixing study to differentiate between Hemophilia A & Anti-Factor 8 Ab
Mix with normal: Hemophilia results in corrected PTT
156
Most common inherited coagulation disorder
VWF deficiency (AD)
157
Inheritance of most common inherited coagulation disorder
AD: VWF deficiency
158
Abnormal ristocetin test
VWF deficiency
159
Treatment of VWF deficiency
Desmopressin; increases VWF release from WP bodies of endothelial cells
160
Vitamin K gamma-carboxylates which coagulation factors?
2, 7, 9, 10, Factors C + S
161
Vitamin K deficiency occurs in which patient populations?
1. Newborns (lack of GI colonization)
2. LTM ABX therapy
3. Malabsorption
162
In what organ is epoxide reductase present?
Liver
163
Effect of liver failure on coagulation is followed using: PT or PTT
PT
164
Platelet destruction that arises 2/2 heparin therapy is called:
Heparin-induced thrombocytopenia: fragments of destroyed platelets may activate remaining platelets leading to thrombosis
165
Heparin complexes with... on the surface of platelets (Think HIT)
Platelet factor 4
166
Pathological activation of coagulation cascade: thrombosis and thrombocytopenia
DIC
167
DIC is 2/2
Obstetric complication, sepsis, AC [mucin], APML, rattlesnake bite
168
Which type of leukemia can lead to DIC?
APML
169
Decreased platelets, increased PT, PTT, decreased fibrinogen, microangiopathic hemolytic anemia, elevated fibrin split products
DIC
170
Product of lysed cross-linked fibrin
D-dimer (fibrin split product)
171
Two examples of excessive fibrinolysis.
1. Radical prostatectomy (release of urokinase that activates plasmin)
2. Cirrhosis of liver (reduced production of alpha-2-antiplasmin)
172
Alpha-2-antiplasmin
Inactivates plasmin (think cirrhosis)
173
DIC vs. disorder of fibrinolysis
Fibrinolysis: normal platelet count; increased fibrinogen split products; no elevation of d-dimers!
174
Symptoms very similar to DIC without elevated d-dimers
Disorder of fibrinolysis
175
Treatment of disorder of fibrinolysis
Aminocaproic acid
176
Most common location of a thrombus
DVT below the knee
177
Lines of Zahn & attachment to a vessel wall [what do these help distinguish]
Both features help distinguish a thrombus from a post-mortem clot
178
Lines of Zahn
RBC, fibrin, RBC, fibrin
179
Three major risk factors for thrombosis [Virchow's triad]
1. Endothelial damage
2. Stasis: stasis or turbulence of blood flow (non-laminar)
3. Hypercoagulable state
180
3 examples of stasis (Virchow's triad)
1. Immobilizaton
2. Cardiac wall dysfunction
3. Aneurysm
181
PGI2 and its vasoprotective effect
PGI2 blocks platelet aggregation
182
Anti-thrombin 3 inactivates
Factor 10 and thrombin
183
Thrombomodulin
Redirects the function of thrombin to activates protein
184
3 major causes of endothelial damage (Virchow's triad)
1. Atherosclerosis
2. Vasculitis
3. High levels of homocysteine
185
High levels of homocysteine can increase risk for thrombosis. Give several examples
1. B12/Folate deficiency
| 2. Cystathionine beta synthase deficiency; Homocystinuria
186
Cystathionine beta synthase deficiency
Results in homocystinuria; characterized by vessel thrombosis, mental retardation, lens dislocation and long, slender fingers
187
6 major causes of hypercoagulable states (Virchow's triad)
1. Lack of protein C/S [Factors 5 & 8]
2. Factor 5 Leiden
3. Prothrombin 20210A
4. AT3 deficiency
5. Lupus anti-coagulant
6. OCP
188
Increased risk for warfarin skin necrosis is seen in patients with
Protein C/S deficiency [increased thrombus formation because of uninhibited 2, 7, 9, 10]
189
The coagulation factors with the very shortest half-life
Proteins C + S [and hence an increased risk for the activation of factors 2, 7, 9, 10]
190
Mutated form of this factor that lacks the cleavage site for deactivation by proteins C & S
Factor 5 Leiden: most common cause of inherited hypercoagulable state
191
Inherited point mutation in prothrombin that results in increased gene expression and promotes thrombus formation
Prothrombin 20210A
192
In patients with an AT3 deficiency, what happens to the PTT when you dose them with heparin
PTT does not rise
193
An intravascular mass that travels and occludes downstream blood vessels
Embolism
194
Most common source of an embolus.
Thrombus
195
The histologic hallmark of an atherosclerotic embolus
Cholesterol cleft in the embolus
196
What type of embolus is associated w/ long bone fractures? What are the presenting features?
Fat embolus
| * Dyspnea & petechiae on the skin overlying the chest
197
Decompression sickness can lead to...
Gas embolus: Nitrogen precipitates as you ascend; p/w joint and muscle pain [Benz] and respiratory symptoms [Chokes]
198
The chronic form of gas embolus is called...
Caisson disease: characterized by multifocal ischemic necrosis of the bone
199
T/F Laparacopic surgery can lead to a gas embolus
T
200
Why can an AF embolus lead to DIC?
Tissue thromboplastin in the amniotic fluid [squamous cells and keratin debris from fetal skin]
201
Keratin debris in the blood vessel of the lung of a female
AF embolus
202
Most common source of DVT
Femoral, iliac or popliteal vein
203
T/F Most PE is clinically silent
T
204
What % of PE cause pulmonary infarction?
10%
| * Pre-existing CP compromise
205
T/F D-dimer is elevated in PE
T
206
What does gross exam of a PE demonstrate?
Hemorrhagic, wedge-shaped infarct
207
What type of PE leads to sudden death?
Saddle embolus
208
Chronic pulmonary emboli can lead to...
Pulmonary HTN
209
Systemic embolism usually arise in the... ? Where is the most common site of occlusion?
Left heart; lower extremities
210
Hb values for anemia in males vs. females
M: < 13.5
F: < 12.5
211
MCV values in different anemias
Microcytic: < 80
Normocytic: 80-100
Macrocytic: > 100
212
T/F Microcytosis is due to an "extra" division 2/2 decreased production of Hb
True: heme or globin
213
4 major causes of microcytic anemia
1. Fe deficiency & 2. ACD
3. Sideroblastic anemia
4. Thalassemia
214
Lack of ____ is the most common nutritional deficiency in the world
Fe
215
Iron is consumed in heme and non-heme. Which is meat derived?
Heme & more readily absorbed
216
Fe is absorbed in the ...
Duodenum; enterocyte
217
Transporter/key regulatory step in Fe absorption biochemistry
Ferroportin [no way to get rid of Fe] ** major site of absorption **
218
________________ transports Fe & delivers it to the liver and bone marrow macrophages for storage
Transferrin
219
Stored IC Fe in liver and macrophages is bound to...
Ferritin
220
Fe-deficiency anemia
| * Infants, children, adults, elderly
Infants: breast feeding
Children: poor diet
Adults: M- PUD; F- Menorrhagia/Pregnancy
Elderly: Colon polyps/carcinoma; hookwork (developing world)
221
The 2 hookworms associated with Fe-deficiency anemia
Necator, Ancylostoma
222
Fe2+ or Fe3+: which is more easily absorbed? Why is this clinically relevant?
Fe2+ : maintained by the acidity of the stomach [decreased Fe2+ w/ GASTRECTOMY]
223
Stages of Fe deficiency
1. Storage depleted
2. Serum depleted
3. Normocytic anemia
4. Microcytic, hypochromic anemia
224
T/F The initial stage of Fe-deficiency anemia is normocytic
True
225
What is RDW?
The spectrum of size of RBC's
* Low is normal
* High is abnormal
226
RDW in Fe-deficiency anemia
Increased
227
Increase/Decrease: Free erythrocyte protoporphyrin in Fe-deficiency anemia
Increased
228
Fe-deficiency anemia with esophageal web & atrophic glossitis. P/W Anemia, dysphagia and beefy-red tongue
Plummer-Vinson Syndrome
| [redundancy of esophageal mucosa]
229
Chronic disease results in increased acute phase reactants. Which one of these is associated with ACD?
Hepcidin: sequesters Fe in storage sites; limits Fe transfer from macrophages to erythroid precursors; suppresses EPO production
230
Increase/Decrease: Free erythrocyte protoporphyrin in ACD
Increased
231
Treatment of ACD in cancer
EPO
232
First step in heme synthesis is RLS. What vitamin is a co-factor?
Succ CoA --> ALA
| * ALAS / B6 *
233
Second step in heme synthesis.
ALA --> Porphobilinogen
| * ALAD *
234
Ferrochelatase is located in what part of the cell?
Mitochondria
235
T/F If protoporphyrin is deficient, Fe remains trapped in mitochondria
True
236
What is the classical cell seen in sideroblastic anemia? Where is the Fe present?
Ringed-sideroblast [iron-laden mitochondria form a ring around the nucleus of erythroid precursors]
237
What special stain marks iron?
Prussian blue
238
Most common congenital defect in sideroblastic anemia?
ALAS deficiency
239
Acquired casues of sideroblastic anemia
EOTH, lead poisoning [ALAD, ferrochelatase], vitamin B6 deficiency
240
T/F Sideroblastic anemia is an Fe-overloaded state
True
241
Carriers of the thalassemia trait are protected against which species of malaria?
Plasmodium falciparum
242
The 3 normal types of Hb seen in humans.
HbA: Alpha2, beta2
HbF: Alpha2, gamma2
HbA2: Alpha2, delta2
243
There are how many copies of the alpha gene in Hb? What chromosome? What is the genetic defect in alpha-thal?
4 in Chromosome 16
| * Gene deletion
244
1-4 genes deleted in alpha-thal. What are the clinical features of each.
1: asymptomatic
2: mild anemia with inc. RBC
[cis vs. trans] Cis is worse than trans, particulary for offspring in Asians [seen in Asians]
3: severe anemia (HbH)
245
cis vs. trans 2x alpha-thal
Cis is worse: Asians [offspring]
| Trans: Africa
246
What is HbH?
Tetramers of beta chains. Seen on 3-gene deletion alpha-thal.
247
Hb Barts
Hydrops fetalis; tetramer of gamma. Lethal in utero.
248
Whereas alpha thal is 2/2 gene deletions, beta thal is 2/2
Mutations of genes: Ch. 11
| [beta null vs. beta plus]
249
Mildest form of beta thalassemia
Beta - Beta+ (Mildest form of disease); target cells
250
The key finding in Hb electrophoresis in beta thalassemia
Increased HbA2, HbF
251
In beta-thal major, when does baby p/w severe anemia?
A few months after birth
252
Alpha tetramers are seen in alpha or beta thal?
Beta thal --> ineffective erythropoiesis
253
Why is there skull and facial bone abnormalities in patients with beta thal, i.e. crew cut X-ray & chipmunk facies?
Expansion of hematopoeisis into marrow of skull and facial bones; extramedullary hematopoesis with HSM; risk of aplastic crisis with parvovirus b19
254
Aplastic crisis vs. aplastic anemia
Crisis: Parvovirus B19 -- erythroid precursors
255
Are target cells seen in beta thal?
Yes
256
Why do you see nucleated RBC's in thal?
If there is extramedullary hematopoeisis & HSM, some of the RBC's escape
257
Vitamin B12 passes its methyl group onto...
Homocystiene --> Methionine
258
How many lobes are there in hyper-segmented neutrophils?
>5
259
Folate is obtained from green vegetables and fruits and is absorbed in...
Jejunum
260
B12 is obtained from animal-derived proteins. It is then cleaved from the proteins & complexes it with ____________ from salivary gland? How and then where is it absorbed?
R-binder
* Pancreatic protease cleaves, then binds with IF; absorbed in ileum
261
Years to develop B12 deficiency or B9?
B12 (strict vegan)
262
#1 cause of B12 deficiency
Pernicious anemia
263
Other causes of B12 deficiency aside from pernicious anemia
Pancreatic insufficiency (R-binder proteases)
* Crohn's or Diphyllobothrium
* Strict vegan
264
Sub-acute combined degeneration of spinal cord
2/2 methylmalonic acid; B12 deficiency
265
How do you differentiate between peripheral destruction or underproduction of RBC in normocytic anemia?
Retic count
266
Why are retics blue on peripheral smear?
RNA within cytoplasm
267
T/F Retic count is falsely elevated in normocytic anemia.
True (BM has not made any extra RBCs). Needs to be corrected * Mult by HCT/45
268
Why is 3% the golden percentage when considering normocytic anemia?
3% good marrow response (peripheral destruction)
269
Hemolyis: IV vs. EV
IV: within BV
EV: RES/macrophages liver, spleen, LN
270
In extravascular hemolysis, the following are broken down to:
Globin: AA
Heme: Fe, protoporphyrin
Protoporphyrin: UC bilirubin
271
What binds free Hb in blood?
Haptoglobin
272
Days after a patient presents with hemoglobinura, he can present with what in his urine?
Hemosiderinuria
| * Hb taken up by PCT, destroyed and forms hemosiderin; PCT slough off
273
Inherited defect of spectrin, ankyrin, or band: RBC cytoskeletal membrane tethering proteins
Hereditary spherocytosis
274
Increased RDW with HS?
Yes
275
Increased MCHC with HS?
Yes
| * Hb becomes more []'ed as cells get smaller
276
What is work hypertrophy of the spleen?
As splenic macrophages work to clear RBC's in conditions, i.e. hereditary spherocytosis
277
Osmotic fragility test + in what disease?
Hereditary spherocytosis
278
Howell-Jolly bodies on blood smear
Post splenectomy [fragment of nuclear material remaining]
279
Treatment of hereditary spherocytosis
Splenectomy
280
Inheritance and genetic defect of SCA
AR mutation in beta-chain of Hv; normal glutamate (hydrophilic) replaced by valine (hydrophobic)
281
What is the underlying pathophysiology in HbS?
HbS polymerizes when deoxygenated; polymerizes aggregate into needle-like structures resulting in sickle cells [not covalent bonding; reversible]
282
Increased risk of sickling under what conditions...
| Any protective medicine?
Hypoxemia, Dehydration, Acidosis
| * HbF / hydroxyurea
283
Target cells in SCA?
Yes; redundancy of membrane
284
Massive erythroid hyperplasia in SCA?
Yes
285
Pathology in SCA is 2/2
1. RBC damage
| 2. Irreversible sickling
286
Swollen hands and feet in an African American infant (dactylitis)
SCA: common presenting sign 2/2 vasoocclusive infarcts of bones
287
What patients have an increased risk of Salmonella osteomyelitis?
SCA
288
AA pt p/w chest pain, SOB, lung infiltrates often precpitipated by PNA
Acute chest syndrome / SCA
| * Vaso-occlusion in pulmonary microcirculation
289
Most common cause of death in SCA adults
Acute chest syndrome
290
Most common cause of death in SCA children
Infection with encapsulated organisms
291
Can SCA p/w acute papillary necrosis?
Yes
292
What is the one area of the body most susceptible to damage in pts w sickle cell trait?
Renal medulla: extreme hypoxia, hypertonicity; microinfarctions; microscopic hematuria and decreased ability to concentrate urine
293
Metabisfulfite screen
Causes cells with any degree of HbS to sickle: both disease and trait
294
AR mutation in beta chain of Hb where glutamate is replaced by lysine. What do you see on peripheral smear?
HbC [ly-seeeeee-ine]
| * Characteristic HbC crystals
295
Acquired defect in myeloid stem cell whereby GPI is no longer present in cell membranes. Results in...
Paroxysmal nocturnal hemoglobinura [breath shallow overnight, acidosis / activate complement]
DAF [c3 convertase] & MIRL protect RBC's against complement ** GPI anchoring protein **
296
Is PNH genetic or acquired?
Acquired
297
Intravascular or Extravascular hemolysis: PNH
Intravascular
298
Sucrose test is used to screen for...
PNH: confirmatory test is acidified serum test of flow cytometery to detect lack of CD55 (DAF)
299
CD55
DAF (GPI-linked membrane protein)
300
Main cause of death in patients with PNH
Thrombosis: destroyed platelets release cytoplasmic contents into circulation inducing thrombosis of hepatic, portal or cerebral veins
301
Complications of PNH
Fe-aneima; AML
302
XLR disorder that reduces RBC t1/2 and renders cells susceptible to oxidative damage
G6PD deficiency
[h2o2 --> glutathione --> h2o]
* NADPH *
303
2 variants of G6PD
Mediterranean: marked reduction
African: Mild
304
Heinz bodies
Oxidative stress (infections, drugs, fava beans) results in (Hb precipitates) Heinz bodies in RBC's that are removed by the spleen and then you get bite cells
305
G6PD: Intra or Extravascular hemolysis
Intravascular
306
Hemoglobinuria and back pain
G6PD deficiency
307
How do you screen for G6PD deficiency? How do you confirm it?
Heinz preparation; confirm w/ enzymatic studies -- not during an episode, but afterward b/c during, all the bite cells will have been consumed
308
IgM vs. IgG AI hemolytic anemia
IgM: Cold, intravascular; fixes complement in extremities
* M. pna, Mono
IgG: Warm, extravascular / spherocytes (similar to HS)
* SLE, CLL, drugs (causes auto-Ab, i.e. methyldopa)
309
To diagnose hemolytic anemia
Coombs test
- Direct: Anti IgG Ab [are the cells already coated with Ih]
- Indirect: Does pt have Ab in serum?
310
What drug is associated with AIHA (warm)
Methyldopa
311
Schistocytes are the hallmark of...
Microangiopathic hemolytic anemia [TTP/HUS, ITP, prosthetic valve, AS]
312
Malaria is transmitted by which mosquito?
Anopheles
313
Daily fever vs. QOD fever in malaria
Daily: P. f
QOD: P vivax, ovale
314
Empty fatty marrow; treatment?
Aplastic anemia; drug cesation, transfusion, EPI, GM-CSF, IS, BMT
315
Pathologic process that replaces bone marrow
Myelophthisic process
316
Myeloid stem cell can produce
RBC
Myeloblast (BEN-G)
Monocyte
Megakaryo
317
2 major causes of neutropenia
1. Drug toxicity
| 2. Severe infection
318
Major causes of lymphopenia
Immunodeficiency (DiGeorge), high cortisol (apoptosis of lymphocytes), AI destruction (SLE), whole body radiation (most sensitive cell)
319
Most sensitive cell to whole body radiation
Lymphocytes
320
Neutrophilic leukocytosis
Bacterial infection, tissue nex, high cortisol
321
Cortisol and its effect on blood elements
High PMN [less adhesion of marginated PMN's to endothelium], low lymphocyte
322
L-shift leukocytosis results in neutrophils with a decreased surface concentration of CD__
Immature, decreased Fc receptors [CD16]
323
CD16
Marker of mature WBC's, decreased Fc receptors [CD16]
324
Monocytosis
Chronic inflammation, malignancy
325
Eosinophilia
Allergy, parasite, Hodgkin lymphoma (IL-5)
326
Basophilia
CML
327
Lymphocytic leukocytosis is seen in which bacterial infection? Think an unvaccinated child.
B. pertussis [lymphocytosis promoting factor]
328
EBV infection results in lymphocytosis with reactive CD8+ T cells
Oropharynx, liver, B cells
* Mono *
* * LAD, splenomegaly (PALS), high white count with atypical lymphocytes
329
Which part of lymph node is hyperplasied in EBV mono?
Paracortex
330
Which part of spleen is hyperplasied in EBV mono?
White pulp; PALS (periarterial lymphatic sheath)
331
IgM heterophile Ab are positive with _____
Mono; Sheep or horse RBC
Can be negative with CMV
332
Definitive test for mononucleosis
EBV viral capsid antigen
333
Complications of mononucleosis
Splenic rupture, rash with PCN, dormancy of virus in B cells
334
Acute leukemia requires what percentage of blasts in BM?
>20%
335
Hallmark marker for ALL
TdT (DNA polymerase marker)
336
Hallmark marker for AML
MPO (Auer rod crystallization)
337
Leukemia & Down Syndrome
AML: < 5 yo [megakary]
ALL: > 5 yo
338
B-ALL surface markers
CD 10, 19, 20
339
Patients with B-ALL have an excellent response to CTX. However, CTX does not cross several barriers and prophylaxis is required in 2 areas.
1. Scrotum
| 2. CSF
340
t(12,21) vs. t(9,22) ALL
t(12,21): good PGX, more commonly seen in kids
| t(9,22): poor PGX, more commonly seen in adults
341
T-ALL surface markers
CD2 thru CD8; do not express CD10
342
T-ALL p/w
Thymic mass in a teenager (Acute lymphoblastic lymphoma)
343
t(15, 17)
t(15, 17) = APML
* RAR receptor disrupted and promyelocytes acumulate; contain numerous Auer rods and hence increased risk for DIC
* ATRA causes blasts to mature
344
Acute monocytic leukemia p/w
Proliferation of monoblasts; lack MPO & blasts characteristically infiltrate the gums
345
Acute megakaryoblastic leukemia
Proliferation of megakaryoblasts; lack MPO; association with Down Syndrome before age 5
346
Myelodysplastic syndromes
Cytopenias with hypercellular marrow; abnormal maturation with inc blasts (20% blasts)
Alkylating agents; rads
347
Co-expression of CD5, CD20 leukemia
CLL: naive B cells; lymphocytes and smudge cells
348
Smudge cells
CLL --> LAD --> SLLymphoma
349
CLL complications
Hypogammaglobulimenia, AIHA, Transformation to DLBL
350
TRAP + cells
Hairy cell leukemia
| * Splenomegaly (red pulp), dry tap, no LAD
351
Splenomegaly with expansion of red pulp and negative LAD and dry tap is seen which which leukemia?
Hairy cell leukemia
352
Hairy cell leukemia has an excellent response to what therapy?
2-CDA (ADA inhibitor)
| Adenosine accumulates to toxic levels in neoplastic B cells
353
HTLV-1
ATLL; Cd4+ T cells
| * Rash, LAD, HSM, lytic bone lesions with hypercalcemia
354
Lytic bone lesions with hypercalcemia & a rash
Multiple myeloma w/o rash, but also HTLV-1 with rash
355
Neoplastic proliferation of mature CD4+ T cells
Mycosis fungoides: rash, plaque, nodules
356
Pautrier microabscesses
Aggregates of neoplastic T-cells in epidermis in mycosis fungoides
357
Sezary syndrome
Characteristic lymphocytes with cerebriform nuclei in mycosis fungoides that spreads to the blood
358
Complications of MDS
Hyperuricemia, marrow fibrosis, acute leukemia
359
Basophils are characterizsticaly increased in...
CML
360
t(9,22)
CML; BCR-ABL fusion [oncogene] with increased TK activity; first line treatment is imatinib
361
Phases of CML
1. Chronic: large spleen
2. Acceleration: enlarging spleen
3. Blast: 2/3 to AML, 1/3 ALL
[mutation in a pluripotent stem cell]
362
When CML progresses to acute leukemia, where is the mutation?
CD34+ hematopoietic stem cell
363
CML vs. Leukemoid reaction: LAP
CML: LAP negative
CML: basophilia
CML: t(9,22)
364
JAK2 kinase mutation drives which myeloproliferative disorders?
PV: blurry vision, thrombosis, flushed face, itching after bathing [mast cells]
& Essential thrombocythemia & MF
365
Treatment PV
Phlebotomy, hydroxyurea
366
PV vs. Reactive polycythemia
PV: EPO decreased
Reactive: EPO increased
OR RCC with ectopic EPO
367
Increased platelets seen in
ET, Fe-deficiency anemia
368
T/F ET rarely progresses to marrow fibrosis, acute leukemia, hyperuricemia
True: platelets do not have nuclei!
369
Why does MF have marrow fibrosis?
[JAK2] Increased megakaryocytes which produce excess PDGF
370
Leukoerythroblastic smear
Myelofibrosis [reticulin gates don't prevent immature blood cells from leaving the spleen with extra-medullay hematopoesis]
371
Teardrop cell
Myelofibrosis
372
Malignant proliferation of plasma cells in bone marrow; most common primary malignancy of bone. What IL is characteristically elevated?
MM; serum IL-6 is high
373
Why does MM result in bone pain with hypercalcemia?
Neoplastic plasma cells activate RANK receptor on osteoclasts
374
M spike on SPEP. Which Ig?
IgG, IgA
375
Multiple myeloma most common cause of death
Infection
376
Rouleaux formation of blood smear
Multiple Myeloma
377
Free light chain circulating in multiple myeloma results in
Primary AL amyloidosis
378
Bence-Jones proteinuria
Free light chain in urine in multiple myeloma
379
Isloated M spike without MM signs/symptoms
MGUS
380
B cell lymphoma with monoclonal IgM
Waldenstrom macroglobulinemia; retinal hemorrhage, stroke, bleeding
381
Pentamer Ig
IgM
382
Acute complications of Waldenstrom Macroglobulinemia
Plasmapheresis
383
What are Langerhans cells?
Specialized dendritic cells found predominantly in the skin; derived from bone marrow monocytes and present Ag to naive T cells
384
Neoplastic proliferation of Langerhans cells
Langerhans cell histiocytosis: Birbeck (tennis racket) granules on EM
385
What cells are CD1a and S100+ on IHC?
Langerhans cell histiocytosis
386
Skin rash, cystic skeletal defects in an infant < 2 y.o. (Langerhan cell histiocytosis)
Letterer-Siew (Malignant proliferation of Langerhans cells)
387
General rules for the subtypes of Langerhans cell histiocytosis
1. Person's name = Malignant
2. 2 names = child < 2 y.o.
3. 3 names = child 3 y.o.
Skin involvement = malignant
388
Subtypes of Langerhan cell histiocytosis
1. Letterer Siew
2. Eosinophilic granuloma
3. Hand-Schuller-Christian
389
Benign proliferation of Langerhans cells in the bone; classic p/w pathologic fx in adolescent; no skin involvement
Eosinophilic granuloma
390
Malignant proliferation of Langerhans cells p/w scalp rash, lytic skull defects, DI, exopthalmos in a child > 3
Hand Schuller Christian disease
391
Painless inflammation
Chronic inflammation, metastatic carcinoma, lymphoma
392
LAD involving:
| Follicles, paracortex, sinus histiocytes
Follicles: RA, early HIV [follicles]
Paracortex: Viral [mono/EBV]
Sinus histiocytes: LN draining tx w ca
393
Cortex, paracortex, medulla of lymph node. Which cells?
Cortex: B cells
Paracortex: T cells
Medulla: sinus histiocytes
394
T/F Lymphoma forms a mass in lymph or extra-nodal tissues
True
395
Name the normal zones of the cortex of a lymph node
In the corex: Follicle, Mantle, Margin
396
Name the small, medium and large cell lymphomas
Small: Follicular, Mantle, Marginal, SLL
Medium: FL
Large: DLBL
397
t(14, 18)
FL; bcl2 over-expression
| * Neoplastic small B cells p/w late adulthood and painless LAD
398
Treatment for symptomatic follicular lymphoma
Low-dose CTX or Rituximab
399
Complication FL
DLBL: p/w enlarging lymph node
400
Lack of tingible body macrophages in germinal centers of follices: follicular hyperplasia or follicular lymphoma
Follicular lymphoma
| * They indicate active apoptosis
401
Expression of BCL2 follices: follicular hyperplasia or follicular lymphoma
Follicular lymphoma
402
t(11,14)
Mantle cell lymphoma (immediately adjacent to follicle); Cyclin D1 [promotes G1/S] -- phosphorylates
403
Marginal zone lymphoma
MALToma
| * Hashimotos, Sjogren's, H. pylori
404
Most lymph nodes don't typically have marginal zones, thus marginal zone lymphoma is associated with...
Chronic inflammatory states
405
BL of the jaw vs. abdomen
c-myc
* Jaw = endemic
* Abdomen = sporadic
406
t(8,14)
c-myc oncogene in BL
407
High mitotic rate and starry sky appearance on histology of lymph node
Burkitt's lymphoma
408
Most common form of NHL; clinically aggressive
DLBL
409
Reed-Sternberg cells
Call in cytokines and drive the inflammatory response
* CD 15, 30
* Hodkins lymphoma
410
Reed-Sternberg cell surface marker
CD15, 30
411
Hodkin's lymphoma subtypes
Nodular sclerosis: mediastinal mass in a young adult female
Lymphocyte rich (best pgx)
Mixed cellularity (IL-5, eosino)
Lymphocyte depleted: worst pgx (HIV)
412
Mixed cellularity HL
IL-5 production by RS cells; eosinophilia
413
Remnant of the mesonephric duct in the lateral vaginal wall.
Gartner duct cyst
414
Prolactin inhibits the release of
GnRH
415
GH adenoma: children vs. adults. What condition is usually present?
Children: gigantism
Adults: acromegaly
* 2 DM
416
Most common cause of death in acromegaly
HF
417
Lack of GH suppression with oral glucose is present in which pituitary disease?
Acromegaly
418
Treatment of Acromegaly
Octreatide, GHR antag, surgery
419
Common cause of hypopituitarism in a child
Craniopharyngioma
420
Poor lactation and loss of pubic hair 2/2 pregnancy
Sheehan syndrome
421
Central DI
2/2 ADH deficiency: hypothalamus or posterior pituitary
422
Nephrogenic DI 2/2 what drug?
Lithium
423
Hyponatremia, low serum osmolality, MS changes and seizures. Common causes
SIADH
* SCLC
* CNS trauma
* Pulmonary infection
* Drugs, i.e. cyclophosphamide
424
Medical treatment of SIADH
Demclocycline
425
Anterior neck mass; cystic dilation of thyrossal duct remnant
Thyroglossal duct cyst
426
Persistence of thyroid tissue at the base of the tongue; P/W base of tongue mass
Lingual thyroid
427
Differentiate between mechanism of increase in BMR vs. SNS activity in hyperthyroidism
BMR: Na-K ATPase
SNS: B1 adrenergic R
428
Heat intolerance vs. Cold intolerance: Hyper/Hypo-thyroidism
Heat intolerance: Hyperthyroid
429
T/F An elderly pt w hyperthyroidism can p/w afib
T
430
Hyperthyroidism: cholesterol and sugar (increased or decresed)
Hypocholesterolemia, Hyperglycemia [GNG/Glycogenolysis]
431
Pre-tibial myxedema & exopthalmos; explain the pathophysiology
Hyperthyroidism
| * Fibroblasts with TSH R; secrete excess GAG's
432
Scalloping of thyroid follicle is classically present in which disease
Grave's disease
433
Thyroglobulin is derived from what AA?
Tyrosine
434
Peroxidation involves (thyroid)
Oxidation, organification, coupling of TG w/ I
435
Treatment of thyroid storm
PTU, beta-blockers, steroids
436
Does PTU block peripheral conversion of T4 to T3?
Yes
437
What is the classicaly cause of multi-nodular goiter?
Iodine deficiency
438
Mental retardation, short stature with skeletal abnormalities, coarse facial features, enlarged tongue and umbilical hernia in a child
Cretinism 2/2 maternal hypothyroidism, thyroid agenesis, dyshormonogeneetic goiter, I deficiency
439
The most important cause of dyshormonogenetic goiter.
Lack of TPO
440
Another name for hypothyroidism in an adult
Myxedema: weight gain, slowing of mental activity, muscle weakness, cold intolerance with decreased sweating
441
2 classic anatomic areas for myxedema in an adult
Larynx (deepening of voice)
| Tongue (enlarged)
442
Can Lithium case hypothyroidism?
Yes
443
HLA-DR5
Hashimoto thyroiditis
444
Which HLA is associated with Hashimoto thyroiditis?
HLA-DR5
445
Anti-microsomal Ab
Hashimoto's thyroiditis
| [markers of damage, rather than mediators of disease]
446
In what condition do you get chronic inflammation with germinal centers and Hurthle cells? Increased risk of marginal zone lymphoma?
Hypothyroidism (Hashimoto's)
| * Yes
447
Young woman with a tender thyroid
Subacute deQuervain granulomatous thyroiditis
448
Chronic inflammation with extensive fibrosis of thyroid that p/w hard-as-wood nontender thyroid. Complications?
Reidel Fibrosing Thyroiditis
| * Involvement to local structures, i.e. airway
449
Anaplastic thyroid ca vs. Reidel Fibrosing thyroiditis
Anaplastic: old people
Reidel: young people
450
They key way by which you bx the thyroid
FNA
451
Benign proliferation of thyroid follicles surrounded by fibrous capsule.
Thyroid follicular adenoma
452
4 types of thyroid ca
1. Papillary (LN, orphan Annie)
2. Follicular (Blood)
3. Medullary (calcitonin, MEN)
4. Anaplastic
453
Major risk factor for the most common type of thyroid carcinoma
Papillary / exposure to ionizing radiation in childhood [radiated for severe acne]
454
Orphan Annie eyes with nuclear grooves & psammoma bodies
Papillary ca of thyroid
455
T/F In both follicular adenoma and follicular carcinoma of the thyroid, the tumor is surrounded by a fibrous capsule.
True! (Ca obviously invades capsule)
456
Can FNA be used to distinguish follicular adenoma from follicular carcinoma of the thyroid?
No
457
The 4 carcinomas that tend to spread hematogenously
1. RCC
2. HCC
3. FC thyroid
4. Choriocarcinoma
458
Calcitonin, amyloidosis: Thyroid cancer
MTC
459
MEN 2A & B are associated with which oncogene?
RET
460
3 major tissues that PTH acts on
1. Kidney: PTH
2. GIT: inc Ca and PO4
3. Bone: clastic
461
Does PTH act on osteoblasts or clasts?
!!Blasts!!: RANKL --> RANKR (clasts)
462
Most common cause of primary hyperparathyroidism
PTH adenoma
463
Osteitis fibrosis cystica is caused by
Hyperparathyroidism
464
Increased or Decreased: Urinary cAMP & Alk Phos in hyperparathyroidism
Increased
465
Is alk phos a sign of osteoblastic or clastic activity?
Blastic
466
Most common cause of 2 hyperparathyroidism
Chronic renal failure
| * Excess serum phosphate binds free Ca
467
Alk phos in all hyperparathyroidism disorders is increased because
Increased osteoblastic activity
468
Causes of hypoparathyroidism
AI damage, surgical excision, DiGeorge syndrome
469
Trousseau sign vs. Chovstek sign
Chovstek: tapping facial n.
Trousseau: fill BP cuff, spasm
470
AD disorder associate with short stature, short 4th and 5th digits, hypocalcemia with increased PTH levels
Pseudohypoparathyroidism
| * End organ resistance to PTH (Gs)
471
PTH is associated with Gs or Gq
Gs
472
HLA-DR3 & DR4 in the context of islet cell inflammation
DM1
473
Why does stress predispose a pt w/ DM1 to p/w DKA
Stress --> Epi --> Glucagon
474
Treatment DKA
Fluids, insulin, K
475
Amyloid deposition in islets
DM2
476
NEG of large/medium vessels and small vessels in DM
Lg/Med: atherosclerosis
| Small: hyaline
477
Which cells in the body are particularly prone to osmotic damage? What is the key enzyme?
Schwann cells, pericytes of retinal blood vessels, lens
| * Aldose reductase *
478
Episodic hypoglycemia with MS changes relieved by glucose
Insulinoma
479
ZES ulcers can extend into...
Treatment-resistant peptic ulcers; may be multiple and can extend into the jejunum
480
Achlorhydria, cholelithiasis, steatorrhea
Somatostatinoma [gastrin/CCK]
481
Watery diarrhea, hypokalemia, achlorhydria
VIPoma
482
Adrenal hormones are derived from...
Cholesterol
483
Why do you see muscle weakness with thin extremities in Cushing syndrome?
Muscle breakdown for GNG; storage for fat in face, neck, trunk
484
Why do you see abdominal striae in Cushings?
Cortisol impairs synthesis of collagen
485
Why do you see HTN in Cushing's?
Cortisol increases alpha-1 R on arterioles
486
Immune suppression in Cushing's syndrome is mediated by:
1. Inhibit PLA2
2. Inhibit IL-2
3. Inhibits histamine release
487
Most common cause of Cushing syndrome
Excess CS: will shut down ACTH production and lead to atrophic adrenal glands
488
2 difference cells aldosterone works on in the kidney
1. Principal cell: dumps K
| 2. Alpha intercalated cell: dumps H+
489
Most common cause of AR congenital adrenal hyperplasia
21-hydroxylase deficiency
| * Clitoral enlargement in females/precocious puberty in males
490
Acute adrenal insufficiency
Waterhouse-Friderichensen syndrome * sac of blood * [lack of cortisol]
491
Chronic adrenal insufficiency
1. AI destruction
2. TB
3. Mets (Lung ca)
492
A high yield cause of hypotension, hyponatremia, hypovolemia, hyperkalemia, weakness, hyperpigmentation, vomiting, diarrhea. Where is the primary malignancy?
Chronic adrenal insufficiency
| * Mets to adrenal from lung
493
Why do you seen hyperpigmentation with excess ACTH?
POMC -- > melanocyte stimulating hormone
494
Color of pheo?
Brown
495
10% rule of pheo
10% b/l, 10% familial, 10% malignant, 10% located outside of adrenal medulla [tihnk about wall of bladder]
496
Several causes of pheo
1. MEN2A, B
2. VHL
3. NF-1
497
A 'myelophthisic' process that reduces normal hematopoiesis and leads to a peripheral 'leukoerythroblastic' picture with immature RBC's and WBC's in the peripheral blood, as seen here with nucleated RBCs and white cells even more immature than bands (metamyelocytes, myelocytes) on the smear
Metatstatic ca
498
AD impaired cartilage proliferation in the growth plate due to activating mutation of...
FGFR3; AD, thought most mutations are new
499
Short extremities with N size head and chest
Achondroplasia
500
IM ossofication vs. EC ossification: Achondroplasia
Achondroplasia: long bone growth problems / problems with endochondral ossification [long bones, cartilage replaced]
501
AD defect in collagen 1 synthesis
Osteogenesis imperfecta; multiple bone fractures, blue sclera and hearing loss [bones of ear]
502
Why are sclera blue in OI?
Exposure of choriodal veins
503
Inherited defect of bone resorption resulting in abnormally thick, heavy bone that fractures easily
Osteopetrosis
504
The carbonic anhydrase II mutation can lead to what disease...
Osteopetoris: lack of acidic environment required for resorption of bone
[acid down pipes can remove calcium]
505
Bone fractures, pancytopenia, vision/hearing loss, hydrocephalus and renal tubular acidosis
Osteopetrosis
506
Treatment of osteopetoris
BMT (monocytes)
507
Defective mineralization of osteoid
Rickets/Osteomalacia 2/2 low vitamin D
508
Pigeon breast deformity, frontal bossing, rachitic rosary [costo-chondro junction deposition of osteoid] and bowing of legs in a child
Rickets
509
Labs in osteomalacia, weak bones with increased risk for fracture
Decreased Ca, PO4
| Increased PTH, ALP
510
Alkaline phosphate creates an acidic/basic environment for osteoblastic activity
Basic environment
511
Loss of trabecular bone mass that results in porous bone
Osteoporosis
512
3 determinants of peak bone mass
1. Diet
2. Exercise
3. Vitamin D receptor
513
Is estrogen protective for bone mass?
Yes
514
Bone pain and fractures in weight bearing areas; bone density low in DEXA scan; normal labs
Osteoporosis
515
Treatment of osteoporosis
Exercise, vitamin D, ca, bisphosphonates, ERT, GC contraindicated
516
Imabalance between osteoblastic and clastic function: viral etiology. Name the disease, its phases and its characteristic histology.
Paget's disease of the bone
1. Clastic
2. Mixed
3. Blastic
4. Sclerotic
* Cement lines / puzzle pieces / mosaic!
517
Etiology of Paget's disease
Possibly viral
518
Isolated elevated ALP
Paget's disease
519
Treatment of early Paget's disease
Calcitonin, bisphosphonates
520
Complications of Paget's disease
High output cardiac failure; osteosarcoma
521
Infection of marrow space and bone; usually occurs in children. What part of the bone does it seed in kids vs. adults?
* Osteomyelitis
Kids: Metaphysis
Adults: Epiphysis
522
Name the parts of bone.
Distal to proximal: EMD
523
Lytic focus of a bone surrounded by sclerosis on X-ray. How do you make the diagnosis?
Osteomyelitis
| * Blood culture
524
Ischemic necrosis of bone / bone marrow 2/2 trauma, fracture, steroids, SCD, Caisson disease (N-emboli)
Avascular, aspectic necrosis
525
Classic example of Avascular, aspectic necrosis in bone of SCD patient
Dactylitis
526
Benign tumor of bone that most commonly arisies on surface of facial bones; can be associated with Gardner syndrome
Osteoma
527
Gardner syndrome
1. FAB
2. Neurofibromatosis retroperit
3. Osteoma
528
Benign tumor of osteoblasts surrounded by rim of reactive bone; occurs in young adults and arises in cortex of long bones
Osteoid osteoma
529
Bone pain of osteoid osteoma is resolved with ___________. What does imaging reveal?
ASA; imaging reveals a bony mass w radiolucent (osteoid) core
530
Bone pain similar to osteoid osteoma that does not resolve with ASA
Osteoblastoma (Arises in vertebreae); > 2cm
531
Most common benign tumor of bone; tumor of bone with an overlying cartilage cap; arises from a lateral projection of growth plate
Osteochondroma
532
Overyling cartilage of an osteochondroma can transform into...
Chondrosarcoma
533
Malignant proliferation of osteoblasts; peak incidence in teenagers & elderly. Risk factors?
Osteosarcoma
| * Familial Rb; Paget disease; radiation exposure
534
Osteosarcoma arises in what part of bone?
Metaphysis of long bones; distal femur/proximal tibia
535
Classic X-ray findings on osteosarcoma. Histology?
Drags periosteum off of the bone = Codman's angle & hazy burst of sunlight
* Large pleomorphic cells producing pink osteoid
536
Bone tumor in the epiphysis of long bones (usually distal femur or proximal tibia) with soap-bubble appearance on X-ray. Locally aggressive and may recur.
Giant cell tumor
537
The only tumor that arises in the epiphysis of bone
Giant cell tumor
538
Malignant proliferation of poorly-differentiated cells derived from.... Arises in the diaphysis of long bones in male children. Onion-skin appearance on X-ray
Ewing sarcoma
539
X-ray appearance of bone tumor:
1. Soap bubble
2. Codman angle/rays of sun
3. Onion-skin
1. Soap bubble: Giant cell
2. Codman angle/rays of sun: osteosarcoma
3. Onion-skin: Ewing sarcoma
540
Ewing sarcoma is a malignant proliferation of cells derived from
Neuroectoderm
541
Small round blue cells of a bone tumor with tumor. Can resemble what conditions?
Ewing sarcoma = t(11,22)
* Bone swelling & fever = osteomyelitis
* Lymphoma
542
t(11,22)
Ewing sarcoma
543
Benign tumor of cartilage; usually arises in medulla of small bones of hand and feet. Malignant arises in the pelvis or skeleton
Chondroma vs. Chondrosarcoma
544
Cartilage tumors usually arise in medulla or cortex of bones?
Medulla
545
Usually, bone mets produce osteolytic, punched out lesions. The one exception is that produces osteoblastic lesions...
Prostate cancer classically produces osteoblastic lesions
546
Describe the anatomy of a synovial joint
Bone, articular cartilage surrounded by joint capsule/synovium that secretes hyaluronic acid
547
Degenerative joint disease
Progressive degeneration of articular cartilage; most often due to wear and tear. Additional risk factors (to age) include obesity and trauma
548
DIP & PIP stiffness, hip, lower spine, knees that worsens during the day
Degenerative joint disease
549
Eburnation of subchondral bone 2/2 disruption of articular cartilage with osteophyte formation (H+B nodes)
Osteoarthritis; Degenerative joint disease
550
HLA-DR4
RA
551
Synovitis leading to pannus
RA
| * Inflammed granulation tissue. Leads to destruction of cartilage and ankylosis of joint
552
Pathologic features of RA
```
Ankylosis: fusion of joints
Joint deviation (myofibroblasts)
Disruption of cartilagel joint space narrowing, osteopenia
```
w/ fever, malaise, weight loss, myalgia
553
Morning, symmetric stiffness that improves with activity
RA
554
DIP is usually spared in: RA or OA?
RA
555
Central necrosis surrounded by epithelioid histiocyte: what type of nodule?
Rheumatoid nodule
556
Swelling of bursa behind the knee: OA or RA
RA
557
Pleural effisions, LAD, interstitial lung fibrosis: RA or OA?
RA
558
anti-Fc IgG IgM Ab
Rheumatoid factor
559
Several complications of anklysoing spondylitis
Uveitis, aortitis [AR]
560
Reiter syndrome
Arthritis, urethritis, conjunctivitis
| * Young male weeks after GI or Chlamydia infection
561
Sausage finger or toe associated with psoriasis
Psoriatic arthritis
562
Infectious arthritis in an adult is caused by
N. gonorrohea
563
2 mechanisms of gout
Increased production urate, poor excretion
564
HGPRT responsible for
HX, G salvage [Lesch-Nyhann syndrome]
565
Podagra
Painful arthritis of the great toe [gout]
566
Why meat and ETOH can trigger gout?
Meat: DNA/RNA
ETOH: compete w/ urate at kidney
567
Chronic gout manifestations
Tophi, renal failure
568
Needle-shaped crystals with negative birefringence under polarized light
* Gout
Lay low = yellow
Parallel light = yellow
569
Pseudogout is 2/2 deposition of
Calcium pyrophosphate; rhomboid shaped crystals with weak + birefringence under polarized light
570
Inflammation of skin and skeletal muscle of unknown etiology (could be associated with carcinoma, i.e. gastric)
Dermatomyositis
571
Bilateral proximal muscle weakness [hair, stairs]; distal involvement; rash of upper eyelids [helioptrope], malar rash, red papules on elbows, knuckles and knees
Dermatomyositis
572
Malar rash that is not SLE; ANA+, Anti-Jo-1 Ab +
Dermatomyositis
573
Anti-Jo-1 Ab
Dermatomyositis
574
Perimysial inflammation (CD4) vs. Endomysial inflammaion (CD8)
Dermatomyositis [closer to the skin] / Polymyositis
575
Treatment of dermatomyositis
CS
576
Replacement of skeletal muscle by adipose tissue occurs in
XLR MD
577
The largest gene in the human genome
Dystrophin (anchors cytoskeletal to the ECM)
578
Proximal muscle weakness at 1 year of age with elevated CK
DMD
579
Death in DMD
Cardiac failure (or resp)
580
What NMJ disorder is associated with Thymic hyperplasia/thymoma
MG
581
Most common benign and malignant soft tissue tumor of adults. What is the characteristic cell in the malignant tumor?
Lipoma/Liposarcoma
| *Lipoblast is characteristic cell
582
Cardiac rhabdomyoma is associated with what syndrome?
Tuberous sclerosis
583
Bening tumor of skeletal muscle
Rhabdomyoma
584
Most common malignant soft tissue tumor in children [think young girl]. What is the positive stain?
Rhabdomyosarcoma; rhabdomyoblast that is desmin+; H+N (vagina in young girls)
585
Derivates
Neural crest cells
Neural tube / wall
Lumen
PNS
CNS
Ventricles/SC canal
586
T/F Anencephaly leads to maternal polyhydramnios
True [absence of CNS swallowing]
587
Congenital stenosis of the channel that drains CSF from the 3rd to 4th ventricle
Cerebral aqueduct stenosis
588
Lateral --> 3rd ventricle
Foramen of Monroe
589
Congenital failure of the cerebellar vermis to develop. P/W massively dilated 4th ventricle with absent cerebelleum
Dandy-Walker Malformation
590
Congenital extension of cerebellar tonsils through Foramen Magnum
Arnold Chiari Malformation
Type 1: no symptoms
Type 2: hydrocephalus
* Meningomyelocele; syringomyelia
591
Cystic degeneration of the spinal cord; arises with trauma or Arnold-Chiari malformation. What level and what sensory loss?
Syringomyelia; C8-T1. Loss of pain and temperature [knocking out of anterior commissure]; also LMN +/- lateral horn
592
Sympathetic innervation to the face and its spinal cord association
Lateral horn of T1
593
Damage to the anterior motor horn 2/2 infection. LMN signs.
Poliomyelitis
594
Inherited degeneration of anterior motor horn. Inheritance pattern and disease
AR; floppy baby [Werdnig Hoffmann disease]
595
Degenerative disorder of upper and lower motor neurons (CS tract)
ALS
Anterior: LMN signs
Lateral CS: UMN signs
596
What distinguishes ALS from syringomyelia?
Lack of sensory impairment in ALS
597
What is the earliest sign of ALS?
Atrophy and weakness of hands
598
In familial cases of ALS, what mutation is present?
Zn-Cu SOD mutation
599
Degenerative disorder of cerebellum and spinal cord tracts; P/W ataxia w/ loss of vibration/proprioception, muscle weakness in LE and loss of DTR
Freidreich Ataxia
| * GAA frataxin gene [cannot regulate Fe properly]
600
What is the underlying pathophysiology in Friedreich Ataxia?
AR unstable GAA repeat in frataxin gene; inability to properly regulate Fe
601
What is the disease associated with Freidreich Ataxia?
Hypertrophic CM
602
Leptomeninges consist of
Pia and arachnoid
603
Meningitis in neonates
GBS, E. coli, L. monocytogenes
604
Meningitis in children/teenagers
N. m
605
Meningitis in adults and elderly
S. pna
606
Meningitis in nonvaccinated infants
H. flu
607
What is the route of transmission of N. m?
Nasopharyngeal
608
What level do you do an LP?
L4-L5: level of iliac crest
609
Spinal cord ends at
L2
610
Normal glucose is approximately what percentage of serum glucose?
66%
611
Complications of bacterial meningitis
Death, hydrocephalus, hearing loss, seizures
612
Etiology of cerebrovascular disease
85% ischemia (focal, global)
| 15% hemorrhage
613
Global cerebral ischemia etiology
Low perfusion (atherosclerosis), shock, chronic hypoxia (anemia), repeated hypoglycemia (insulinoma)
* Mild
* Moderate: infarcts in watershed areas
* Severe
614
Describe mild, moderate and severe global cerebral ischemia
Mild: insulinoma
Moderate: infarcts in watershed areas
Severe: death
615
What histological layers of the brain are most susceptible to damage during global ischemia?
* End of ACA, MCA
* Pyramidal neurons of the cortex layers 3, 5, 6 = Cortical laminar necrosis
* Pyramidal neurons of hippocampus
* Purkinje layer of cerebellum
616
What is cortical laminar necrosis?
Areas of the brain most susceptible to damage during decreased perfusion: layers 3, 5, 6 of cortex (also pyramidal neurons of the hippocampus)
617
Focal ischemia of the brain results in...
Stroke (<24 h = TIA)
618
3 ways to develop an ischemic stroke
1. Thrombotic [pale at periphery of cortex]
2. Embolic [red]
3. Lacunar [hyaline arteriolosclerosis -- most commonly involves the lenticulostriate vessels]
619
Lacunar stroke
Ischemic stroke 2/2 hyaline arteriolosclerosis most commonly involves the lenticulostriate vessels
620
Lenticulostriate vessels arise from and supply the...
MCA / deep structures of the brain
621
Ischemic stroke leads to what type of necrosis?
Liquefactive; red neurons are early finding; PMN/microglial/granulation tx; results in a fluid-filled cystic space surroudned by gliosis
622
What is the earliest change (histologically) in an ischemic stroke?
Red/pink neurons [12-24 hours]
623
What are the 2 types of cerebral hemorrhage?
1. Intracerebral
| 2. SA
624
Intracerebral hemorrhage is classisically 2/2
Rupture of Charcot-Bouchard microaneurysm as a complication of HTN; basal ganglia is the most common site
625
Charcot-Bouchard microaneurysm p/w
HA, nausea, vomiting, coma
626
LP with xanthochromia
SA hemorrhage
627
Most frequent cause of SA hemorrhage
Rupture of berry aneurysm; thin-walled saccular outpouching that lacks a media layer; most often located in anterior circle of Willis
628
What layer of a blood vessel's wall is absent in a berry aneurysm?
Media
629
Lucid interval is seen in...
Epdural hematoma
630
Lethal complication of epidural hematoma
Brain herniation
631
Lethal complication of subdural hematoma
Brain herniation
632
Tonsillar herniation
Herniation of cerebellar tonsils through FM --> CP arrest
633
Subfacline herniation
Cingulate gyrus herniates under falx --> compress the ACA
634
Uncal herniation
Uncus of temporal lobe; CN 3, PCA, Duret hemorrhages
635
Duret hemorrhages
Consequence of uncal herniation
636
Inherited mutation in ezymes necessary for production or maintenance of myelin
Leukodystrophy
637
Deficiency of arylsulfatase; myelin cannot be degraded and thus accumulates in lysosomes
Metachromatic leukodystrophy
638
Deficiency of galactocerebroside B- galactosidase
Krabbe disease
639
Impaired addition of coenzyme A to LCFA; fatty acids accumulate damaging adrenal gland and white matter
Adrenoleukodystrophy
640
HLA DR-2
MS
641
AI destruction of CNS myelin and oligodendrocyte; seen in regions away from the equator
MS
642
Blurred vision in one eye, vertigo/scanning speech and internuclear opthalmoplegia
MLF
643
LP with lymphocytes, Ig with oligoclonal IgG bands and myelin basic protein
MS
644
Acute attack of MS treated with vs. LTM
Acute: high dose steroids
LTM: IFN-beta
645
Progressive, debilitating encephalitis leading to death. Due to slowly progressing, persistent infection of brain by what virus?
Mealses; SSPE
| * Viral inclusions in gray /white matter
646
JC infection of oligodendrocytes p/w rapidly progressing neurology and death
PML; IS leads to reactivation of latent virus
647
PML vs. SSPE
SSPE: Measles [white and gray]
PML: JC virus
648
Focal demyelination of the pons that p/w locked in syndrome
Central pontine myelinosis; due to rapid IV correction of hyponatremia
649
Degeneration of gray neurons in cortex vs. basal ganglia
Cortex: dementia
| Basal ganglia: gray matter
650
Degenerative disease of the cortex
Alzheimer disease
651
APP receptor broken down to a beta product which is then deposited as... [in the brain]
AB amyloid
652
Major risk factor for sporadic Alzheimer's is...
Age, APOE4
653
APOE4 vs. APOE2 and Alzheimer's risk
APOE4: higher number/increased risk
APOE2: lower/decreased risk
654
Early onset Alzheimer's a/w
1. Pre-synelin 1 [mutation] & 2
| 2. Down' syndrome [APP on Ch. 21]
655
Presenilin 1 mutation
Alzheimers
656
Gross specimen of an Alzheimer's brain
Diffuse cerebral atrophy, narrowing of gyri, widening of sulci
* Hydrocephalus ex vacuo [atrophy of brain 2/2 loss of parenchyma]
657
Hydrocephalus ex vacuo
[atrophy of brain 2/2 loss of parenchyma]
| * Alzheimer's
658
A neuritic plaque in Alzheimer's
1. AB amyloid (from APP)
- -can deposit around BV/cerebral amyloid amylopathy
2. Neuritic processes
659
NF tangles are seen in...
Alzhemier's: intracellular / tau proteins (MTOC proteins)
660
Hyperphosphorylated tau proteins
Microtubular associated protein seen in intracellular accunulations in Alzheimers [hyperphosphorylated]
661
Multifocal infarction and injury 2/2 HTN, atherosclosis, or vasculitis
Vascular dementia
662
Degenerative disease of frontal and temporal cortex
```
Pick disease (tau protein aggrgates)
* Behavior and language
```
663
NF tangles vs. round aggregates of tau proteins
Tangles: Alzheimer's
Round: Pick disease
664
The striatum receives input from
Cortex and SN pars compacta; can send stimulatory or inhibitory signals to the cortex
665
D1 vs. D2 receptors
D1: increase stimulation
D2: decrease inhibition
666
Rare exposure to MPTP in drugs can lead to what disease?
Parkinson's disease
667
Lewy bodys
Parkinson's [composed of alpha synuclein]
668
Synuclein vs. Sineilin
Synuclein: Parkinson's
Sinelin: Alzheimer's
669
Early-onset dementia in Parkinson's = (vs. late onset)
Lewy body dementia
670
Degeneration of GABAeric neurons in the caudate nucleus of the basal ganglia
Huntington disease
671
The striatum is composed of
Caudate & Putamen
672
GABA is a stimulatory/inhibitory NT
Inhibitory (GABAeric neurons and Huntington's disease)
673
What structures sit just laterally to the lateral ventricles?
Striatum (caudate----IC----putamen)
674
Anticipation is due to...
Further expansion of the trinucleotide repeat during spermatogenesis
675
Chorea, athetosis, demention, depression, suicide
Huntington's disease
676
Increased CSF that leads to dilated ventricles
NPH; can cause dementia in adults; LP releives symptoms
677
NPH vs. Hydrocephalus ex. vacuo
NPH:
| Ex vacuo:
678
NPH triad
Dementia, gait instability, urinary incontinence [wet, wacky, wobbly]
679
The nerve fibers running along the ventricles
Corona radiata
680
Treatment of wet, wobbly, wacky disorder?
LP/shunt [NPH]
681
Arachnoid granulations
Drain the CSF
682
Degenrative disease 2/2 prion protein
Spongiofrm encephalopathy
683
PrP --> PrP SC
Beta-pleated sheet
* Pathologic / cannot degrade
* Spongy holes in white gray matter [intracellular vaculoes]
684
Etiology of spongiform encephalopathy
1. Sporadic
2. Inherited
3. Transmitted
685
CJD is usually sporadic; but can arise due to exposure to prion infected human tissue
Human growth hormone; corneal transplant
| * P/W rapidly progressive dementia a/w ataxian and startle myoclonus; spike-wave complexes seen on EEG
686
Spike-wave complexes on EEG
CJD
687
vCJD is related to exposure to...
Bovine spongiform encephalopathy (mad cow disease)
688
Familial fatal insomnia
Inherited form of prion disease characterized by insomnia and exaggerated startle response
689
What 3 cancers classically metastasize to the brain?
Lung, breast, kidney
690
What cells in the brain form the blood brain barrier?
Astrocytes
691
Malignant high grade tumor of astrocytes; most common malignant CNS tumor in adults
GBM; crosses corpus collosum
692
GBM histologic hallmarks & IHC marker
1. Large amount of necrosis
2. Edge of necrosis/ pseudopallasading
3. Endothelial cell proliferation
* GFAP + (derived from glial cell)
693
Most common benign brain tumor in adults
* Meningoma
| Benign tumor of arachnoid cells; F>M; p/w seizure.
694
What receptor is expressed by meningioma brain tumor?
Estrogen receptor
695
Benign brain tumor with wholrled cells & psammoma bodies
Meningioma
696
Benign tumor of Schwann cells; IHC marker
Schwannoma, S100+, B/L NF-2
697
S100+ brain tumor
Schwannoma
698
Calcifed tumor in white matter of frontal lobe p/w seizure
Oligodendroglioma; malignant
699
Histology of oligodendroma
Fried egg
700
Most common brain tumor of chidlren p/w cyst + neural nodule on MRI
Pilocytic astrocytoma (benign)
701
Histologic hallmark of pilocytic astrocytoma
Rosenthal fibers
702
Malignat tumor derived from the granular cells of the cerebullum. Histology
Medulloblastoma [neuroectoderm]
| * Arises in children; small, round blue cells w/ Homer-Wright rosettes. Poor pgx
703
Homer-Wright rosettes vs. Rosenthal fibers
HW: Medulloblastoma
Rosenthal: pilocytic astrocytoma
704
T/F A medulloblastoma grows rapidly, spreads via CSF and can p/w drop mets
T
705
Malignant brain tumor of children. Most commonly arises in the 4th ventricle; may p/w hydrocephalus
Ependymona
706
Homer-Wright rosettes vs. Perivascular pseudo-rosettes vs. Rosenthal fibers
Homer W: Medulloblastoma
Perivascuar pseudorosettes: Ependymoma
Rosenthal fibers: pilocytic astrocytoma
707
Tumor that arises from he epithelial remnants of Rathke's piouch
Carniopharyngioma
708
Upward protrusion of the floor of the mouth
Rathke's pouch = AP
709
T/F Craniopharyngioma is calcified on imaging
True
710
Hypospadias
Opening of the urethra on the inferior surface of the penis (ventral)
* Failure of the urethral folds to close
711
Epispadias
Opening of the urethra on the superior surface of the penis 2/2 abnormal positioning of the genital tubercle
* A/W Bladder extrosphy
712
Epispadias is a/w
Bladder extrosphy
713
Condyloma acuminatium
Benign warty growth on genital skin 2/2 HPV 6, 11 characterized by koilocytic change [raisin like nuclei]
714
Necrotizing granulomatous inflammation of inguinal lymphatics and lymph nodes
Chlamydia trachomatis [OIC]
| * Heals w fibrosis and perianal involvement may result in rectal strictures.
715
LGV vs. chancroid vs. condyloma lata vs. condyloma accuminatum
LGV: C. trachomatis
Chancroid: H. ducreyi
CL: Syphillis
CA: HPV
716
Chlamydia serotypes
A-c: trachoma
D-k: UG + conjunvtivitis
L1-L3: LGV
717
Risk factors for SCC penis
High risk HPV (2/3); lack of circumcision
718
Precursor lesions to SCC penis
Bowen disease: shaft
Erythroplasia of queyrat: glans
Bowenoid papulosis: reddish papules
719
Bowen disease
Precursor lesions to SCC penis (shaft); in situ carcinoma -- leukoplakia
720
Erythroplasia of Queyrat
Precursor lesions to SCC (glans) penis -- erythroplakia
721
Bowenoid papulosis
Precursor lesions to SCC penis (reddish papules)
722
Failure of testicle to descend into the scrotal sac
Cryptoorchidism
723
#1 congenital male reproductive abnormality
Cryptoorchidism
724
Complications of cryptoorchidism
Testicular atrophy w/ infertility [lower temperature] and increased risk for seminoma
725
Orchitis 2/2
Chlamydia D-K, Neisseria, E. coli, Pseudomonas, Mumps, AI
726
Hallmark of AI orchitis
Tubular granulomas (non nex)
727
Twisting of spermatic cord; leads to hemorrhagic infarction 2/2 congenital failure of testes to attach to inner lining of scrotum
Testicular torsion
728
Adolescent with sudden onset testicular pain and absent cremasteric reflex
Testicular torsion
729
Dilation of spermatic vein 2/2 impaired drainage. P/W scrotal swelling with bag of owrms appearance
Varicocele; usually left-sided with L- RCC
730
T/F Varicocele is seen in a large percentage of infertile males
T
731
Fluid collection within the tunica vaginalis; a/w incomplete closure of processus vaginalis (infants) or blocakge of lymphatic drainage (adults); transillumination +
Hydrocele
732
2 types of testicular tumors
1. Germ cell
| 2. Sec-cord stroma
733
Are testicular tumors biopsied?
No -- risk of seeding scrotum; must be removed via radical irchiectomy
734
>95% of testicular tumors are categorized ...
| Risk factors
Germ cell tumor; ages 15-40
* Risk factors = cryptochidism and Klinefelter syndrome
* Divided into seminoma & non-seminoma
735
Dysgerminoma in the ovary. _____________ in the testes
Seminoma
736
Seminoma vs. Non-seminoma: Responds to radiation, metastazies late and has an excellent prognosis
Seminoma
737
Seminoma vs. Non-seminoma: Poor/variable response to treatment and metastazies early
Non-seminoma
738
Can rare cases of seminomas produce beta-HCG?
Yes
739
Homogenous malignant tumor of testicle with no hemorrhage or necrosis
Seminoma [lg cells with clear cytoplasm]
740
Malignant testicular tumor of immature, primtive cells that may form glands; hemorrhage w nex; agressive; CTX can result in differentiation [i.e. a teratoma]. Increased AFP/beta-HCG
Embryonal carinoma
741
Relief of pain with lifting tests
Positive Prenh sign: epididymitis (vs. torsion)
742
Can embryonal ca of testes form glands?
Yes
743
Most common testicular tumor in children. Serum marker? Histology?
Yolk sac tumor; AFP positive
| * Schiller Duvall body
744
What can male chioriocarcinoma lead to? Why?
Hyperthyroidism or gynecomastia (alpha subunit of beta-HCG is similar to FSH, LH, TSH)
745
What is the one cancer (classically) that p/w a tiny primary, but massive secondaries?
Choriocarcinoma
746
Teratoma is benign or malignant in males?
Malignant
747
T/F Most male germ cell tumors are mixed.
T
748
Sex cord stomal tumors of testes
Leydig cell: androgen [Reinke cell crystals]
| Sertoli cell: tubules
749
Most common cause of testicular mass in males over 60
Lymphoma; often B/L & usually DLBL
750
Acute prostatitis in young vs. old males
Young: C/Ng
Old: E coli, Pseudomonas
751
BPH is related to what hormone?
DHT
752
BPH occurs in what zone of the prostate?
Periuretheral
753
Treatment of BPH
Prazosin (alpha-antag), Tamsulosin; 5-alpha-reductase inhibitor
754
Risk factors for prostate AC
Age, race (AA vs. Asians), diet high in saturated fats
755
Most common location for prosate AC
Posterior periphery
756
Decreased % of free PSA in the serum
Suggestive of PRCA. Cancer makes bound PSA
757
T/F Nuclei contain dark nucleoli in PRCA
True
758
Gleason grading is based on architecture or nuclear atypia
Archictecture
759
Low back pain with increased ALP, PSA, PAP
PRCA (osteoblastic mets)
760
PRCA local disease treatment
Prostatectomy
761
Continuous GnRH analog used to treat PRCA
Leuprolide
762
Androgen receptor inhibitor used to treat PRCA
Flutamide
763
Type I HSR of the skin a/w asthma and allergic rhinitis
```
Atopic dermatitis (Eczema)
* Pruritic, erythematous, oozing rash with vesicles and edema
```
764
Ezema usually involes
The face & flexor surfaces
765
Contact dermatitis irritants
Poson ivy, nickel (type 4 HS), detergents, drugs (PCN)
766
Comedones, pustules, nodules
Acne (Comedone = white/blackhead)
767
The pathophysiology of Acne
Excess sebum & keratin; P. acnes /lipases break down sebuml inflammation leads to pimples
768
What skin condition can isotretinoin be used for?
Acne (vitamin A derivative)
| * Decereases keratin production
769
Well-circumscribed salmon-colored plaques with a silvery scale on extensor surfaces and scalp with pitting of nails
Psoriasis
770
HLA-C
Psoriasis
771
Psoriasis is 2/2
Excessive keratinocyte proliferation [ often in an area of trauma]
772
Acanthosis
Excessive epidermis
773
Parakeratosis
Nucleated keratinocytes
774
Monroe microabscesses
Collection of PMN's in the S. corneum (psoriasis)
775
Elongation of dermal papillae contributes to what sign seen in psoriasis?
Psoriasis
| * Pinpoint bleeding = Auspitz sign
776
PUVA treatment for what skin condition?
Psoriasis (psoralen + UVA light)
777
Pruritic, planar, polygonal, purple papules w/ reticular white lines on surface (Wickham striae) involving wrists, elbows and oral mucosa
Lichen planus
778
Inflammation at the dermal-epidermal junction is seen in what skin disorder? Saw-tooth appearance
Lichen planus
779
Lichen planus is associated with what virus?
HCV
780
Anti-desmoglein IgG
PV
781
Acantholysis
Separation of keratinocytes
782
Oral mucosa: PV or BP
PV
783
Blisters that rupture easily vs. those that don't rupture easily
Easily: PV
| Not easily: BP
784
AI deposition of IgA at the tips of dermal papillae that pw/ pruritic vesicles and bullae that are grouped
Dermatitis herpetiformis [celiac disease cross-reactive Ab]
785
HSR with targetoid rash and bullae; most commonly seen with HSV, but can be seen w infections, i.e. mycoplasma, PCN, SLE, malignancy
Erythema multiforme
786
Erythema multiforme with oral mucosa involvement and fever. What is the most severe form called?
SJS; TEN (2/2 ADR)
787
Benign proliferation of squamous cells in the skin p/w pseudocyts on histology and a raised, stuck on lesion; common in the elderly
Seborrheic keratosis [raised discolored, stuck on]
788
Leser-Trelat sign
Sudden onset multiple seborrheic keratoses; suggests and underlying carcinoma of GIT
789
Epidermal hyperplasia with darkening of skin (velvet-like); involves the groin/axilla; associated with insulin resistance or malignancy (gastric ca)
Acanthosis nigricans
790
Risk factors squamous and basal cell ca
Prolonged exposure to sunlight, albinism, xeroderma pigmentosum
791
UV- A, B, or C is most dangerous
UV-B
792
Xeroderma pigmentosum
AR: nucleotide excision repair pathway
| [thymidine dimers]
793
Which skin cancer is surrounded by teleangectasias (w peripheral palisading)? Where is the most classic location?
Basal cell ca; upper lip
794
Additional risk factors for SCC skin
IS therapy, arsenic poisoning, chronic inflammation (scar from burn or draining sinus tract)
795
Upper lip vs. lower lip skin cancer
Upper: Basal
Lower: Squamous
796
Precursor to squamous cell carcinoma of the skin; p/w hyperkeratotic, scaly plaque on face, back or neck
Actinic keratosis
797
Very well-differentiated SCC of skin; develop rapidly and regresses spontaneously; presents as a cup-shaped tumor filled with keratin debris
Keratoacanthoma
798
Melanocytes are dervied from
Neural crest
799
Melain is synthesized in what organelle?
Melanosomes --> passed to keratinocytes
800
AI destruction of melanocytes
Vitiligo (localzied loss of skin pigmentation)
801
What enzyme defect in albinism?
Tyrosinase
802
What are freckles?
Small, tan-brown macules; darkens when expsed to sunlight; due to increased numbers of melanosomes
803
Mask like hyperpigmentation of cheeks A/W pregnancy and OCP
Melasma
804
Benign neoplasm of melanocytes
Nevus (congenital p/w hair)
805
Nevus vs. melanoma
Nevus: has hair growing from it
806
Junctional nevus
Grows along the dermal-epidermal junction [children]
807
Compound nevus
Nevus that grows down into the dermis
808
Intradermal nevus
Most common in adults
809
Junvtional vs. Intradermal nevus
Junctional: children
Intradermal: adults
810
Inheritance: Dysplastic nevi that may progress to melanoma
Dysplastic nevus syndrome: AD
811
Growth phases of melanoma & most important feature for mets
1. Radial (horizontally) -- low risk mets
| 2. Vertical (key feature for mets)
812
Subtypes of melanoma (4)
1. Lentigo (radial - good pgx)
2. Superficial spreading (radial - good pgx)
3. Nodular (early vertical - poor pgx)
4. Acral lentigionus: palms/soles in dark-skinned individuals; not related to UV light exposure
813
Superficial bacterial skin infection 2/2 S. aureus or S. pyogenes p/w erythematous macules that progress to pustules on face (honey-colored serum)
Impetigo
814
Deeper dermal infection 2/2 S. aureus or S. pyogenes p/w/ red, tender, swollen rash with fever
Cellulitis (surgery, trauma, insect bite)
815
Necrosis of SC tissue 2/2 anaerobic flesh eating bacteria
Necrotizing fasciitis: CO2/crepitus
816
Sloughing of skin with erythematous rash and fever
Staph Scalded Skin Syndrome [epidermolysis of s. granulosum / exfoliative A & B toxin]
817
SSS vs. TEN
SSS: S. granulosum
TEN: DEJ
818
Verruca on hand/feet is 2/2
Wart: flesh-colored papule with rough surface 2/2 HPV infection of keratinocytes
819
Firm, pink umbilicated papules 2/2 pox virus [bodies = inclusions]
Molluscum contagiousm
