Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MOD II > Exam 1 > Flashcards

Exam 1 Flashcards

1
Q

What are the two components of tumors

A

Neoplasticism cells that constitute the parenchyma and reactive stroma made up of connective tissue, bv, and cells of the immune system; *growth and spread dependent on stroma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is a desmoplasia

A

Neoplasm where the parenchyma cells stimulate formation of collagenous stroma; *ie: cancers of the breast; can make them stony hard, referrered to as scirrhous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are adenomas

A

Benign epithelial neoplasms arising from glands

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are papillomas

A

Benign epithelial neoplasms producing finger like or warty projections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is a polyp

A

When a neoplasms produces a visible projection above a mucosal surface (if in glandular tissue, called adenomatous polyp)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are sarcomas

A

Malignant tumors arising in solid mesenchymal tissues (fibrosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are carcinomas

A

Malignant neoplasms of epithelial cell origin (derived from germ layers)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is an example of a mixed tumor

A

Mixed tumor of salivary gland; contains epithelial components scattered with a myxoid stroma that may contain cartilage or bone; all arise from a single clone capable of producing both epithelial and myoepithlial cells *called pleomorphic adenoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is a dermoid cyst

A

Ovarian cystic teratoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are hamartomas

A

Disorganized benign masses composed of cells indigenous to involved site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is a choristoma

A

Heterotropic rest of cells; ie: well developed and normally organizers pancreatic tissue in submucosa of stomach

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the tumors of mesenchymal origin

A

Benign: fibromyalgia, lipoma, chondroma, osteoma
Malignant: Fibrosarcoma, Liposarcoma, Chondrosarcoma, osteogenic sarcoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the tumors of vessels and surface coverings

A

Benign: hemangioma, lymphangioma, benign fibrous tumor (from mesothelium), meningioma
Malignant: angiosarcoma, lymphangiosarcoma, mesothelioma, invasive meningioma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the tumors from blood cells and related cells

A

Only malignant types: leukemia and lymphoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the tumors of muscle origin

A

benign: Leiomyoma (smooth m) and rhabdomyoma (striated)
Malignant: leiomyosarcoma, rhabdomyosarcoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the tumors of epithelial origin

A

Benign: squamous cell papilloma (strat squamous), adenoma, papilloma, cystadenoma, bronchial adenoma, renal tubular adenoma, hepatic adenoma, transitional cell papilloma (urinary tract), hydatidiform mole, Nevus (melanocytes)
Malignant: squamous cell carcinoma; basal cells carcinoma (basal cells of skin or adnexa), adenocarcinoma, papillary carcinomas, cystadenocarcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatocellular carcinoma, transitional cell carcinoma, seminoma and embryonal carcinoma (germ cells), malignant melanoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the mixed tumors

A

Benign: pleomorphic adenoma
Malignant: malignant mixed tumor of salivary origin, Wilms tumor (renal anlage)
***derived from ONE germ layer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the teratogenous tumors

A

Benign: mature teratoma, dermoid cyst
Malignant: Immature teratoma, teratocarcinoma
*** derived from more than one germ layer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is anaplasia

A

Lack of differentiation of tumor; considered hallmark of malignancy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Are benign or malignant tumors well differentiated

A

Benign; malignant exhibit wide range of differentiation and most exhibit alternations that betray their malignant nature

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What other morphological changes is often associated with anaplasia

A
  • pleomorphism: variation in size and shape (tumor giant cells)
  • abnormal nuclear morphology: nuclei are disproportionately large w/ nuclear:cytoplasm ratio of 1:1; nuclear shape irregular and coarsely clumped (hyperchromatic)
  • mitoses: many cells in mitosis (atypical, bizarre mitotic figures)
  • loss of polarity: grow in disorganized fashion
  • can develop large areas of ischemic necrosis because require large vascular supply
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is carcinoma in situ

A

Dysplastic changes that involve the full thickness of the epithelium but does not penetrate basement membrane; once it breaches, is referred to as invasive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What forms the capsule in benign tumors

A

ECM deposits stimulated by hypoxic damage resulting from pressure of expanding tumors; does not limit growth of tumor, but rather creates. The tumor to be discrete, readily palpable, moveable and easily excusable: exception - hemangiomas -> may not be able to be respected because unencapsulated and permeate the site in which they arises

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are examples of malignancies that do not often metastasize

A

Gliomas and basal cell carcinomas; invade but do not met

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How can cancers spread

A
  • direct seeding of body cavities or surfaces: most often in peritoneal cavity; particularly characteristic of ovaries (can fill cavity with pseudomyxoma peritonei: gelatinous neoplastic mass)
  • lymphatic spread: most common for carcinomas but sarcomas can also use this route; sentinel LN = first node in regional lymphatic basin that receives lymph flow from primary tumor;
  • hematogenous spread: typical of sarcomas, but also seen with carcinomas; veins more easily penetrated; liver and lungs most frequently involved; vertebral Mets associated with carcinomas of prostate and thyroid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What cancers have a propensity for invading veins

A

Renal cell carcinoma: renal vein -> IVC sometimes to right side of heart
Hepatocellular carcinomas: portal and hepatic radicles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Where does breast carcinoma spread

A

Bones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Where does bronchogenic carcinoma typically spread

A

Brain and adrenals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Where does neuroblastoma typically spread

A

Liver and bones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are the most common tumors in men

A

Prostate, lung and colon/rectum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What are the most cancers in females

A

Breast, lung, and colon/rectum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What cancer causes the most deaths in women

A

Lung

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What tumors are Hispanics at risk for

A

Stomach, liver, uterine cervix, and gallbladder, and certain leukemia’s

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What cancers does alcohol consumption put people at risk for

A

Carcinomas of oropharynx (except lip), larynx, esophagus, and hepatocellular carcinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Which cancers are thought to be linked to diet

A

Prostate, breast, and colorectal carcinomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Are carcinomas typically seen in children

A

No - extremely rare

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What are the common cancers seen in children

A

Small round blue cell tumors: neuroblastoma, wilms tumor, retinoblastoma, acute leukemia’s, and rhabdomyosarcomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What are the acquired predisposing conditions of cancer

A

Chronic inflammations, precursor lesions, immunodeficiency states

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Tumors arising in the setting of acute inflammations are usually _________

A

Carcinomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What are the chemicals involved in “occupational cancers” and what cancers do they cause

A 
Arsenic: lung and skin carcinoma
Asbestos: Lung, esophageal, gastric, colon carcinoma, mesothelioma 
Benzene: AML
Beryllium: lung carcinoma
Cadmium: prostate carcinoma
Chromium: Lung carcinoma
Nickel: lung and oropharyngeal carcinoma
Radon: lung carcinoma
Vinyl chloride: hepatic angiosarcoma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What are the chronic inflammatory states that lead to cancer

A

Asbestosis/silicosis: mesothelioma, lung carcinoma
IBD: colorectal carcinoma
Lichen sclerosis: Vulvar squamous cell carcinoma
Pancreatitis: pancreatic carcinoma
Chronic cholecystitis: GB cancer
Reflux esophagitis: esophageal carcinoma
Sjogren, hashimoto: MALT lymphoma
Gastritis/ulcers: cholangiocarcinoma/ colon carcinoma
Hepatitis: hepatocellular carcinoma
Osteomyelitis: carcinoma in draining sinuses
Chronic cystitis: bladder carcinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What are examples of precursor lesions

A

Inflammatory precursor lesions: Barrets esophagus, bronchial squamous metaplasia, colonic metaplasia of stomach (pernicious anemia nad chronic atrophic gastritis)
Non-inflammatory: endometrial hyperplasia, leukoplakia (thickening of squamous epithelium in oral cavity or penis/vulva -> squamous carcinoma)
Benign neoplasms: colonic follows adenoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What are the steps involved in carcinogenesis

A
  • initiation: exposure to carcinogenic agent; alters cell making it potentially capable of giving rise to a tumor; *initiation alone NOT significant for tumor formation
  • initiation causes permanent DNA damage; rapid and irreversible and has memory; tumors are produced even if promoting agent is delayed for several months
  • promoters induce tumors to arise from initiated cells, but they are nontumorigenic by themselves; promoter affects are reversible
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What are all initiating chemical carcinogens

A

Highly reactive electrophiles that react with nucleophilic sites in the cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What are direct acting carcinogens

A

Do not require conversion to become carcinogenic; chemotherapeutic drugs are example

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What is an ultimate carcinogen

A

Product of metabolism of indirect acting carcinogen; *tobacco

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What are polymorphisms of CYP1A1 linked to

A

Lung cancer; variations in P-450 gene help determine susceptibility to cancer due to indirect carcinogens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What are “hotspots”

A

Spots in the genome with specific DNA sequences that carcinogens target; ie: aflatoxin B (produced by aspergillosis) -> associated with hepatocellular carcinoma causes G:C ->T:A transversion in codon 249

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What are promotors of chemical carcinogenesis

A

Chemical agents that are not mutagenic but instead stimulate cell proliferation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What is the difference between melanoma and nonmelanoma skin cancers

A

Nonmelanoma: associated with total UV exposure
Melanoma: associated with intense intermittent exposure (sunbathing)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Which UV ray is responsible for causing cutaneous cancers

A

UVB (280-320_

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What is the most common cancer caused by radiation

A

Myeloid leukemia’s, then cancer of the thyroid (but only in the young)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Which retrovirus is implicated in cancer of humans

A

Human T cell leukemia virus type I; causes adult T cell leukemia/lymphoma; T cells major target of virus; requires trasmission via bodily fluid; high fraction of tumors express FOXP3 -> opportunistic infections often cause of death; HTVL does not contain an oncogene and does not integrate next to a proto oncogene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

What special gene does HTVL-1 contain

A

Tax: essential for viral replication, and alters transcription of host cell genes
*impt for development of cancer hallmarks -> increased pro-growth signaling and cell survival (stimulates AKT and NFkB and upregulates cyclin D2); increased genomic instability: interferes with DNA-repair functions and inhibits cell cycle checkpoints

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

What are the oncogenic DNA viruses

A

HPV, EBV, Hep B, Merkel cell polyoma, kaposi sarcoma herpesvirus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

What are the high risk HPV strains

A

16 and 18 -> integrated into genome; interrupts viral DNA within E1/E2 open reading farm, leading to loss of E2 viral repressive and overexpression of E6 and E7 which are oncoproteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What does E6 do

A

Binds to and mediated degredation of p53 and stimulates expression of TERT whic his a subunit of telomerase ; *p53 Arg72 is much more likely to develop cervical carcinomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

What does E7 do

A

Binds RB and displaces the E2F, promoting progression through cell cycle; also inactivates CDK inhibitors p21 and 27; also activate cyclins E and A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

What is needed for carcinogenesis of HPV

A

Need to be co-transferred with a mutated RAS gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

What are the proteins that act as oncogenes in EBV

A
  • LMP-1: behaves Iike active CD40 receptor, activates NFkB and JAK.STAT t hat promote B cell survival and proliferation; prevents apoptosis by activating BCL2
  • EBNA-2: mimic active notch receptor; activates cyclin D and SRC family of protooncogenes
  • vIL-10: prevents macrophages from activating T cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Do burkitt lymphoma cells express LMP-1, EBNA-2?

A

No

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Which translocation is involved in burkitt lymphom

A

8:14 (MYC)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Is EBV directly oncogenic in Burkitt Lymphoma

A

No; sets stage for acquisition of 8:14 translocation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

What is different about B cell lymphomas in immunosuppressed individuals in comparison to Burkitt lymphoma

A

They express LMP-1 and EBNA2; also usually lack MYC translocations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

What is nasopharyngeal carcinoma associated with

A

EBV infection; develop IgA abs before tumor; LMP-1 expressed and activated NFkB (upregulates VEGF, FGF-2, MMP9 and COX2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

Do HBV or HCV encode any viral oncoproteins

A

No; mechanism for HBV thought to be virus causing damage and constant repair leading to genomic damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

What is H pylori associated with

A

Gastric adenocarcinomas and gastric lymphomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

How does H pylori cause gastric adenocarcinoma

A

Causes increased epithelial proliferation in setting of chronic inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

What do h pylori strains associated with gastric adenocarcinoma contain

A

Cytotoxin associated A (CagA); penetrates into gastric epithelial cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

How are gastric lymphomas cured

A

Antibiotic therapy to h pylori (removes stimulation of T cells); causes MALT lymphomas -> B cell lymphomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

What is cancer cachexia associated with

A

Equal loss of fat and lean m, elevated basal metabolic rate, systemic inflammation (increased acute phase proteins)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

What are paraneoplastic syndrome

A

Cancer-bearing individuals who develop signs and symptoms not explained by the anatomic distribution of their cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

Why are paraneoplastic syndromes important to recognize

A

Can be earliest manifestation of neoplasm, can cause significant clinical problems, can mimic metastatic disease and confound treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

What is an endocrinopathy

A

Ie: Cushing syndrome; common in persons with carcinoma of the lung (small cell) -> have elevated serum pro-opiomelanocortin and corticotropin (former is not found in serum of patients with excess corticotropin produced by pituitary)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

What is the most common paraneoplastic syndrome

A

Hypercalcemia; causes osteoclasts and production of calcemic humoral substances by extraosseous neoplasms (only later is paraneoplastic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

What humoral factors are associated with paraneoplastic hypercalcemia of malignancy

A

Parathyroid hormone related protein: resembles PTH and share a GPCR; produced in small amounts by keratinocytes, m, bone, and ovary; regulates calcium transport into a rating breast and across placenta; *most associated with CA of breast, lung (squamous cell carcinoma), kidney, and ovary
-IL-1, TGF alpha, TNF, dihydroxyvitamin D also play a role

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

What is acanthosis nigricans

A

Gray-black patches of thickened hyperkeratotic skin with a velvety appearance; in ppl over 40, associated with cancer; associated with gastric, lung, and uterine carcinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

What is hypertrophic osteoarthropathy

A

Associated with lung carcinoma; characterized by periosteal. New bone formation (distal ends of long bones, metatarsals/carpals, and prox phalanges), arthritis of adjacent joints and clubbing of digits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

What cancers are Trousseau syndrome most often associated with

A

Lung and pancreas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

What cancer is DIC most commonly associated with

A

Acute promyelocytic eukemia and prostatic adenocarcinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

What are nonbacterial thrombotic endocarditis

A

Nonbacterial fibrinous vegetations on cardiac valve (more on left) found in individuals with mucin secreting adenocarcinomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

What is grading of tumors dependent on

A

Degree of differentiation of tumor cells and sometimes the number of mitoses or architectural features

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

What is staging of cancer dependent on

A

Size of primary lesion, extent of its spread to regional LN, and presence or absence of blood born Mets; uses TNM system; primary lesion T1-T4 based on increasing size (T0 is in situ), N0-N3 for involvement of LN in increasing number and range, and MO-M2 indicating presence of Mets and number

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

What kinds of cancers are cytologic smears most usefu for

A

Endometrial carcinoma, lung carcinoma, bladder and prostatic tumor, gastric carcinomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

What are the limits of cytology and histology in cancer diagnosis

A

Hard to determine tumor type especially of poorly differentiated tumors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

What is immunohistochemistry used to do

A
  • categorize undifferentiated malignant tumors: use abs to intermediate filaments - cytokeratins for epithelial (carcinoma), desmin for m
  • determines site of origin of met tumors: ie: PSA and thyroglobulin
  • Detects molecules that have prognostic or therapeutic significance: ie: hormone receptors in tumors (better breast CA prognosis); can also stain for products of oncogene (HER2 -> poor prognosis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

What is flow cytometry used for

A

To identify antigens expressed by blood forming tissues (B and T cell lymphomas and leukemia’s, and myeloid neoplasms); *multiple antigens can be assessed simultaneously

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

What is used to determine polyclonal versus monoclonal proliferation’s

A

PCR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

What is the translocation seen in Ewing sarcoma

A

11;22 q24;q12

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

What cancer has the PML-RARA fusion gene

A

Acute promyelocytic leukemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

What cancer is associated with BRAF mutation

A

Melanoma, hairy cell leukemia’s, colon cancers, papillary thyroid carcinoma, langerhans cell histiocytes is

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

What hormones are used as tumor markers and for which cancers

A
  • hCG: trophoblastic or nonseminomatous testicular tumors
  • calcitonin: medullary carcinoma of thyroid
  • catecholamine: pheochromocytoma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

What are the incidental antigens used as tumor markers

A
  • alpha fetoprotein: liver cell cancer, nonseminomatous germ cell tumors of testis
  • carcinoembryonic antigen: carcinomas of the colon, pancreas, lung, stomach, and heart
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

What isoenzymes are used as tumor markers

A
  • prostatic acid phosphatase: prostate cancer

- neuron specific enolase: small cell cancer of lung, neuroblastoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

What are immunoglobulins used as a marker for

A

Multiple myeloma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

What mucin are used as tumor markers

A
  • CA-125: ovarian cancer
  • CA-19-9: colon cancer, pancreatic cancer
  • CA-15-3: breast cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

What cell free DNA markers are used as tumor markers

A
  • TP53, APC, RAS mutants in stool and serum: colon cancer
  • TP53, RAS mutants in stool and serum: pancreatic cancer
  • TP53, RAS mutants in sputum and serum: lung cancer
  • TP53 mutants in urine: bladder cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

PSA test has ______ specificity and _______ sensitivity

A

Low; low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

What is DALY

A

Disability adjusted life year: sums of years of life lost due to premature mortality and the years of life lost to disability in a population

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

What is the life expectancy free of disability for women and men

A

Men: 58.3
Women: 61.8

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

What is the single leading global cause of health loss

A

Undernutrition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

What is the leading cause of death in developed countries

A

Ischemic heart disease and CV disease; risks are smoking, high BP, obesity, high cholesterol and alcohol abuse

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

In developing countries, half of the leading causes of deaths are ________

A

Infections diseases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

What are half of the deaths in children younger than 5 attributed to

A

Pneumonia, diarrheal diseases, and malaria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

What are the categories of emerging infectious diseases

A
  • diseases caused by newly evolved strains or organisms
  • diseases caused by pathogens endemic in other species that jumped to human populations *HIV
  • diseases caused by pathogens that have been present in human populations but show a recent increase in incidence (dengue fever)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

What are xenobiotics

A

Exogenous chemicals in air, water, food, and soil that may be absorbed via inhalation, ingestion, or skin contact; almost always lipophilic and metabolized to water soluble substances or are activated to form toxic metabolites

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

What are the two phases of metabolization of xenobiotics

A

I: undergo hydrolysis, oxidation or reduction
II: products from phase I are metabolized into water soluble products via glucoronidation, sulfation, methylation and conjugation with glutathione

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

What is the most important catalyst of phase I Reactions

A

Cytochrome P 450 (in ER of liver mostly); they are heme containing enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

What can decrease CYP activity

A

Starvation or fasting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

How do inducers of CYPs work

A

Bind to nuclear receptors which heterodimerize with retinoic X receptor to form transcriptional activation complex that associates with promoter elements of CYP gene; example of receptor is style hydrocarbon receptor, peroxisome proliferator activated receptor, constitutive androstane receptor and pregnane x receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
111
Q

What makes up smog

A

Sulfur dioxide, lead, carbon monoxide, ozone, nitrogen dioxide, and particulate matter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
112
Q

What is ground level ozone

A

Gas formed by reaction of nitrogen oxides and volatile organic compounds in presence of sunlight; produces free radicals which injure epithelial cells in respiratory tract and type I alveolar cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
113
Q

What can sulfur dioxide cause

A

Burning sensation in nose and throat, difficulty breathing, and asthma attacks in susceptible individuals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
114
Q

What is soot involved in

A

Aka particulate matter; pulmonary inflammation nad secondary CV effects; fine or ultra fine particles less than 10 micrometers are most harmful -> phagocytosed -> inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
115
Q

What is carbon monoxide

A

Systemic asphyxiant; nonirritating, colorless, odorless produced from incomplete oxidation of hydrocarbons (engines, furnaces, cigs); chronic poisoning can occur in ppl working underground, in tunnels, and highway toll booths

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
116
Q

How does CO kill

A

CNS depression (especially in basal ganglia and lenticular nuclei) and systemic hypoxia (occurs when Hbg is 20-30% saturated with CO) unconsciousness and death likely with 60-70% saturation; diagnosis made by measuring carboxyhemoglobin levels in blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
117
Q

What are the characteristics of acute CO poisoning

A

In light skinned individuals, present with cherry red color of skin and mucous membranes; with longer exposure, brain can become edematous with punctuate hemorrhage’s and hypoxia-induced neuronal changes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
118
Q

What are the indoor pollutants

A

Cigarette smoke, NO, CO

  • wood smoke: contains oxides of N and C pollutants; irritant that can cause lung infections and contain polycyclic hydrocarbons (carcinogens)
  • Bioaerosols: can cause legionnaires, viral pneumonia, or common cold, OR allergens from pet dander, dust mites, and fungi
  • Radon: derived from uranium present in soil and homes can cause lung CA in miners; low level exposure not a risk
  • formaldehyde: problem in refugees from environmental disasters living in poorly ventilated trailers-> carcinogen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
119
Q

What harmful effects can lead have

A

Binds to sulfhydryl groups in proteins and interferes with calcium metabolism which leads to hematologic, skeletal, neuro, GI, and renal toxicities

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
120
Q

When is treatment for lead poisoning mandated in children

A

When blood lead levels exceed 45 micrograms/dL; but subclinical lead poisoning can occur below this level (includes subtle deficits in intellectual capacity, hyperactivity, and poor organizational skills)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
121
Q

Where is most of absorbed lead incorporated

A

Into bones and teeth where it competes for calcium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
122
Q

What feature of lead poisoning dominated in adults

A

Peripheral neuropathy we

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
123
Q

Do children or adult absorb more lead

A

Children; the higher absorption and more permeable BBB creates high susceptibility to brain damage in children; causes inhibition of NT caused by disruption of calcium homeostasis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
124
Q

What levels of lead (in microg/mL) cause certain symptoms in children

A

10: developmental toxicity
20: decreased nerve conduction velocity
40: decreased hemoglobin synthesis
100: encephalopathy
150: death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
125
Q

What are the pathological features of lead poisoning in adults

A

Brain: headache, memory loss
Gingiva: lead line
Blood: anemia, red cell basophilic stippling
Peripheral nerves: demyelination
Kidney: chronic tubulointerstitial disease
GI: Ab pain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
126
Q

What are the pathological features of lead poisoning in children

A

Brain: encephalopathy, mental deterioration
Bones: radiodense deposits in epiphyses; inhibits healing of fractures by increasing chondrogenesis and delaying cartilage mineralization

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
127
Q

What enzymes does lead inhibit

A

Aminolevulinic acid DH and ferrochelatase: both involved in heme synthesis; latter catalyze incorporation of iron into protoporphyrin; causes microcytic hypochromic anemia stemming from suppression of hemoglobin synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
128
Q

How do you diagnose lead poisoning

A

Elevated Levels of lead in blood or free red cell protoporhyrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
129
Q

Describe the morphology of lead poisoning

A

Inhibition of ferrochelatase causes appearance of ring sideroblasts, which are red cell precursors with iron laden mitochondria that are detected with Prussian blue stain; causes brain edema and demyelination and necrosis of cortical neurons accompanied by diffuse astrocytic proliferation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
130
Q

What are the first mm to be affected by lead poisoning in adults

A

Extensor mm of wrist and fingers (causes wrist drop) followed by perineal mm causing foot drop

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
131
Q

What are the harmful effects of mercury

A

Binds to sulfhydryl groups in proteins leading to damage in CNS and kidney; *contaminated fish, metallic mercury released from dental amalgams

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
132
Q

What is especially sensitive to methyl mercury

A

Developing brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
133
Q

What allows methyl mercury and Metallic mercury to accumulate in the brain

A

Lipid solubility

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
134
Q

What is the main protective mechanism against mercury

A

Intracellular glutathione

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
135
Q

What are the harmful effects of arsenic

A

Toxicities in GI tract, nervous system, skin and heart; present in Chinese and Indian herbal medicine; arsenic trioxide is treatment for acute promyelocytic leukemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
136
Q

What are the most toxic forms of arsenic

A

Arsenic trioxide, sodium arsenide, and arsenic trichloride; causes acute GI, CV an CNS toxicities that are often fatal; attributed to interference with ox phos

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
137
Q

What are the characteristics of arsenic poisoning

A
  • neur effects 2-8 weeks after exposure consisting of sensorimotor neuropathy that causes paresthesias, numbness, and pain
  • chronic exposure causes skin changes consistent of hyperpigmentation and hyperkeratosis
  • increased risk for development of CA, particularly of lungs, bladder and skin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
138
Q

How do arsenic induced skin tumors differ from those caused by sunlight

A

Often multiple and usually appear on palms and soles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
139
Q

What are the harmful effects of cadmium

A

Preferentially toxic to kidneys and lungs *relatively modern problem; mining and batteries; food is most important source of exposure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
140
Q

What does the uptake of cadmium require

A

Transporters such as ZIP8 (normally transports zinc)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
141
Q

What are the principle toxic effects of cadmium

A

Obstructive lung disease caused by necrosis of alveolar epithelial cells and renal tubular damage that can progress to ESRD; can also cause skeletal abnormalities associated with calcium loss *in japan causes disease of osteomalacia and osteoporosis with renal disease; also have elevated risk of lung CA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
142
Q

What is Minimata disease

A

Exposure of fetus to high levels of mercury -> leads to CP, deafness and blindness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
143
Q

What can exposure to organic solvents cause

A

Ie: chloroform and carbon tetrachloride; used in degreasing and dry cleaning; causes dizziness and confusion, leading to CNS depression and even coma; lower levels toxic to kidneys and liver; *exposure to benzene increases risk of leukemia (oxidized to toxic metabolites by CYP2E1 that disrupt differentiation of hematopoietic cells in BM leading to risk of acute myeloid leukemia)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
144
Q

What can exposure to polycyclic hydrocarbons cause

A

Released during combustion of fossil fuels; present in tar and soot; most potent carcinogens -> lung and bladder CA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
145
Q

What can exposure to organochlorines cause

A

Synthetic lipophilic products that resist degredation; used as pesticides (DDT-used as insecticide in malaria areas), dioxin also an example; disrupts hormonal balance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
146
Q

What can dioxins and PCBs cause

A

Skin disorders such as folliculitis and dermatosis known as chloracne -> acne, cyst formation, hyperpigmentation, and hyperkeratosis generally on face and behind ears; can also cause abnormalities in liver and CNS; PCBs induce CYPs -> abnormal drug metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
147
Q

What does inhalation of mineral dust cause

A

Chronic, nonneoplastic lung disease known as pneumoconioses, most commonly from exposure to coal dust, silica, asbestos, and beryllium *exposure of asbestos extends to family members of those exposed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
148
Q

What does exposure to vinyl chloride cause

A

Angiosarcoma of liver, uncommon type of liver CA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
149
Q

What does exposure to bisphenol A (BPA) cause

A

*lines water bottles; causes endocrine disruption; linked to heart disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
150
Q

How long does the risk of lung cancer persist after smoking cessation

A

30 years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
151
Q

What is the direct irritant effect of cigarette smoke on the lungs

A

Causes inflammation and increased mucus production (bronchitis); also causes recruitment of leukocytes with increased elastase production leading to emphysema

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
152
Q

What are the most important chemicals in cigarette smoke implicated in cancer

A

Polycyclic hydrocarbons and nitrosamines; CYPs metabolize these carcinogens, some intermediates of which can form DNA adducts which can cause mutations in oncogenes and tumor suppressors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
153
Q

What are the organ specific carcinogens in tobacco smoke

A

Lungs and larynx: polycyclic hydrocarbons, NNK, polonium 210
Esophagus: NNN
Pancreas: NNK
Bladder: 4-aminobiphenyl, 2-naphthylamine
Oral (smoking):polycyclic aromatic hydrocarbons, NNK, NNN
Oral (snuff): NNK, NNN, polonium 210

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
154
Q

Which of the tobacco constituents is carcinogenic

A

Tar, polycyclic aromatic hydrocarbons, benzopyrene, nitrosamines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
155
Q

Which of the smoke constituents are toxic to cilia

A

Nitrogen oxides, formaldehyde

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
156
Q

Which of the tobacco smoke constituents are tumor promotors

A

Phenol, and nicotine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
157
Q

Besides lung cancer, what other diseases is smoking linked to

A
  • esophageal, pancreatic, bladder, kidney, cervical and bone marrow cancer
  • nonmalignant conditions -> emphysema, chronic bronchitis, COPD
  • atherosclerosis, MI (due to increased platelet aggregation, decreased myocardial oxygen supply accompanied by increased demand)
  • spontaneous abortions and preterm birthday and intrauterine growth retardation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
158
Q

How can you measure passive smoke inhalation in non smokers

A

Blood levels of cotinine (metabolite of nicotine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
159
Q

What happens to alcohol in the blood

A

Oxidized to acetaldehyde in liver by alcohol DH, ethanol oxidizing system (at high BAC levels) and catalase (very minor importance); acetaldehyde then metabolized. To acetate by acetaldehyde DH, which is then used in mit respiratory chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
160
Q

Where does oxidation by alcohol DH take place

A

Cytosol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
161
Q

Where is the CYP 450 system located

A

ER

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
162
Q

Where does oxidation of acetaldehyde occur

A

Mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
163
Q

What is the microtonal oxidation system

A

CYPs (particularly CYP2E1) located in SER; alcohol induces CYPs -> when alcohol high in the blood, delays other drug metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
164
Q

What is acetaldehyde responsible for the development of

A

Oral cancers; also Asians have very low acetaldehyde DH activity due to substitution of lysine for glutamine at residue 487; even one deficient copy renders activity ineffective because dominant negative -> causes nausea, flushing, tachycardia, and hyperventilation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
165
Q

What is the effect of alcohol oxidation on NAD/NADH

A

Reduces NAD to NADH; NAD is required for FA oxidation in liver and conversion of lactate into pyruvate -> deficiency causes fatty liver in alcoholics and lactic acidosis (increases NADH/NAD ratio)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
166
Q

What does alcohol cause the release of in the gut

A

Endotoxins from gran negative bacteria in intestinal flora -> stimulates production of TNF and other cytokines leading to hepatic injury

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
167
Q

Where does acute alcoholism exert its main effects

A

CNS, can induce reversible hepatic and gastric changes (acute gastritis/ulceration)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
168
Q

What does chronic alcoholism cause

A
  • liver: alcoholic hepatitis and cirrhosis -> portal HTN and increased risk of hepatocellular carcinoma
  • GI: massive bleeding from gastritis, gastric ulcer, esophageal varices
  • thiamine (B1) deficiency: causes peripheral neuropathies and wernicke’s korsakoff syndnrome, cerebral atrophy, cerebellar degeneration and optic neuropathy
  • CV: dilated congestive cardiomyopathy, increased risk of HTN and decreased HDL (increasing coronary heart disease)
  • acute and chronic pancreatitis
  • CA of oral cavity, esophagus, liver and in women, breast
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
169
Q

What are the characteristics of fetal alcohol syndrome

A

Microcephaly, growth retardation, facial abnormalities in newborn and reduction in mental functions and child grows older *first trimester particularly harmful

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
170
Q

What is the agent responsible for alcohol-induced laryngeal and esophageal cancer

A

Acetaldehyde

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
171
Q

Which kind of alcoholics are at increased risk for developing cancer of the esophagus

A

Individuals with one copy of ALDH2*2 allele

172
Q

What positive effects can moderate amounts of alcohol (250 mL of win/day) have?

A

Increase HDL, inhibit platelet aggregation, lower fibrinogen levels (lowers risk of coronary heart disease)

173
Q

At what level does alcohol cause drowsiness

A

200 mg/dL

174
Q

What is an example of a injury by therapeutic drugs

A

Discoloration of the skin due to the antibiotic minocycline -> causes deposition of drug metabolites/iron/melanin in the dermis

175
Q

What are the two drugs that cause most frequent adverse reactions

A

Warfarin and dabigatran (anti-coagulants) latter is direct inhibitor of thrombin (used in a fib patients); complications include bleeding, thrombotic implications such as embolic stroke stemming from under treatment

176
Q

What is a complication of menopausal hormone therapy (MHT)

A

Increased risk of breast CA, stroke, and venous thromboembolism; no effect on incidence of coronary heart disease

177
Q

What is the risk:benefit consensus of MHT

A
  • combo estrogen-progestin increases risk of breast CA; estrogen alone in women who had a hysterectomy is associated with decreased risk of breast CA
  • protective effect on development of atherosclerosis and coronary artery disease in women < 60 but no protection that started at older age
  • increases risk of stroke and venous thromboembolism
178
Q

Do OCPs increase breast CA Risk

A

No

179
Q

What is the effect of OCPs on endometrial and ovarian cancers

A

Protective

180
Q

What is the effect of OCPs on cervical cancer

A

Increases risk to women who have been infected with HPV

181
Q

What is the effect of OCPs on CV disease

A

Does not increase risk in women younger than 30 or in older women who are nonsmokers; but risk does double in women older than 35 who smoke

182
Q

What can OCPs cause in terms of the liver

A

Hepatic adenoma; rare benign hepatic tumor especially in older women who have used OCPs for prolonged periods

183
Q

What effect do anabolic steroids cause

A

Inhibits production and release of LH and FSH and increases estrogens; stunted growth, acne, gynecomastia, testicular atrophy, growth of facial hair and menstrual changes; psychiatric disturbances and increased risk of MI

184
Q

How is acetaminophen detoxified

A

In the liver by phase II enzymes -> excreted in urine as glucuronate or sulfate conjugated; very small amount metabolized by CYPs to NAPQI which is a highly reactive metabolite (accumulates when taken in large doses and causes hepatocellular injury leading to centrilobular necrosis and liver failure)

185
Q

What are the mechanisms of NAPQI damage on the liver

A
  • covalent binding to hepatic proteins which causes damage to cellular membranes and mit dysfunction
  • depletion of GSH (NAPQI is conjugated to it), which makes hepatocytes more susceptible to ROS injury
  • *toxicity can occur in low doses when drinking alcohol
186
Q

What does acetaminophen toxicity present as

A

Starts with N/V, diarrhea, shock, jaundice; can be treated within 12 hours by administration of N-acetylcystein which restores GSH levels

187
Q

What do ointments containing oil of wintergreen have?

A

Methyl salicylate -> aspirin

188
Q

What does acute salicylate overdose cause

A

Alkalosis as a consequence of stimulation of respiratory center of medulla, this is followed by acidosis and accumulation of pyruvate and lactate caused by uncoupling of oxphos and inhibition of keens cycle; acidosis enhances formation of non-ionized forms of salicylate which diffuse into brain and cause nausea or coma

189
Q

What is chronic aspirin toxicity

A

Salicylism; may develop in persons who take 3 gm or more daily for long periods of time for treatment of chronic pain; manifested by HA, dizziness, ringing in ears (tinnitus), hearing impairment, mental confusion, drowsiness, N/V/D; CNS changes can progress to convulsions and coma; acute erosive gastritis

190
Q

What can mixtures of aspiring and phenoacetin (metabolite is acetaminophen) cause over several years

A

Tubulointerstitial nephritis with renal papillary necrosis -> called analgesic nephropathy

191
Q

What are the affects of cocaine on the CV system

A

Blocks reuptake of dopamine in CNS and blocks reuptake of epi/norepi at adrenergic nerve endings while stimulating release of norepi -> leads to tachycardia, HTN, peripheral vasoconstriction; can also induce myocardial ischemia b y causing coronary artery vasoconstriction and enhancing platelet aggregation and thrombus formation; can also cause lethal arrythmias by disrupting normal ion transport

192
Q

What is the effect of cocaine on the CNS

A

Hyperpyrexia and seizures

193
Q

What are the effects of cocaine on pregnancy

A

Acute decreases in blood flow to placenta resulting in fetal hypoxia and spontaneous abortion; neuro development can be impaired in fetus

194
Q

What are examples of opiates

A

Oxycodon and heroin

195
Q

What are the effects of heroin on the CNS

A

Euphoria, hallucinations, somnlolence and sedation

196
Q

What toxicity does quinine cause

A

Neuro, renal and auditory

197
Q

What are the adverse effects of heroin

A
  • sudden death: drug purity usually unknown -> respiratory depression, arrhythmia, cardiac arrest and pulm edema
  • pulmonary injury: edema, septic embolism from endocarditis, lung abscess, opportunistic infections, foreign-body granuloma (from talc; usually lung but also found in spleen, liver, and LN that drain UE)
  • infections: skin, heart valves, liver, lungs; *endocarditis (usually tricuspid) most caused by S aureus; viral hep most common infection
  • cutaneous lesions (abscesses, cellulitis, ulcerations)
  • kidney disease: amyloidosis secondary to skin infections and glomerulosclerosis (induce protein and nephrotic sydrome)
198
Q

How does methamphetamine work

A

Released dopamine in the brain which inhibits presynaptic NT at corticostriatal synapses, slowing glutamate release; long term use leads to violent behaviors, confusion, and psychotic features

199
Q

What is MDMA

A

Ecstasy; causes increase of serotonin release in CNS; as it wears off causes a drop in serotonin; also reduces number of serotonergic axon terminals in striatum and cortex and increases peripheral effects of dopamine

200
Q

What is marijuana used to treat

A

Nausea and pain

201
Q

What effects does marijuana have

A

Distorts sensory perception and impairs motor coordination; increases heart rate and can cause angina in someone with coronary artery disease

202
Q

Which drug is used more by women than men

A

Tranquilizers

203
Q

What are the classifications of burns

A
  • superficial: first degree burns; confined to epidermis
  • partial thickness burns: second degree burns; involve injury to dermis
  • full thickness burns: third degree burns; extend to subcutaneous tissue; can also involve m (4th degree burns)
204
Q

What are the greatest threats to life of a burn victim

A

Shock, sepsis, and respiratory insufficiency

205
Q

What is a pathophysiologic effect of burns

A

Development of hyper metabolic state associated with heat loss and increased need for nutritional support

206
Q

What is the most common infection seen in burn victims

A

Psudomonas aeurginosa

207
Q

What is the most common complications due to infection in a burn victim

A

Pneumonia or septic shock with renal failure or acute respiratory distress syndrome

208
Q

How can the airway be obstructed in burn victims

A
  • direct effect of heat to mouth, nose and upper airways
  • inhalation of heated air and gases - chlorine, sulfur oxides, ammonia can react with water to form acids or alkalis producing inflammation in upper airways; lipid soluble gases such as NO are more likely to. Reach deeper airways producing pneumonitis
209
Q

What is the morphology of full-thickness burns

A

White or charred, dry and painless because of destruction of nerve endings

210
Q

What is the morphology of partial thickness burns

A

Pink or mottled with blisters and painful

211
Q

What is the histology of a burn

A

Area undergoes coagulation necrosis with adjacent skin has accumulation of inflammatory cells and exudation

212
Q

What are heat cramps, exhaustion, and stroke

A

Cramps: results from loss of electrolytes via sweating; cramping of voluntary mm; able to maintain normal body temp
Exhaustion: most common; sudden onset with prostration and collapse; results from failure of CV system to compensate for hypovolemia
Stroke: associated with high temperatures, humidity and exertion; older adults, ppl undergoing intense physical stress, and ppl with CV disease are at risk; thermoreg. Fails, sweating ceases, and body temp rises -> multiorgan dysfunction

213
Q

What are the characteristics of heat stroke

A

Vasodilation with peripheral pooling of blood and decreased effective circulating blood volume; hyperkalemia, tachycardia, Arrhythmias common; *sustained m contractions that exacerbate hyperthermia and lead to m necrosis (rhabdomyolysis); stems from nitrosylation of ryanodine receptor 1 -> allows Ca to leak into cytoplasm (mutated RYR1 in malignant hyperthermia -> heat stroke like in response to anesthetics)

214
Q

What are things that can lower body temp

A

High humidity, wet clothes, dilation of superficial blood vessles from ingestion of alcohol

215
Q

What occurs at body temp of 90 degrees

A

Loss of consciousness followed by bradycardia and a fib

216
Q

What are the direct effects of hypothermia

A

Mediated by physical disruption within cells by high salt concentrations caused by crystallization of intra and extracellular water

217
Q

What are the indirect effects of hypothermia

A

Results from circulatory changes which vary depending on rate of temp drop; slow chilling can induce vasoconstriction and increase vascular permeability (edema and hypoxia) ie: trench foot; with sudden persistent chilling, vasoconstriction and increased viscosity of blood can cause ischemic injury and degeneration of nerves (vascular injury only evident after temp returns to normal_

218
Q

What are the types of injuries caused by electrical injuries

A

Burns or ventricular fibrillation/cardiac respiratory center failure resulting from disruption of normal electrical pulses

219
Q

What is an important characteristic of alternating current (in homes)

A

Induces tetanic m spasm so irreversible clutching is likely to occur ; can cause spasm of chest wall and asphyxia

220
Q

What is nonionizing radiation

A

UV, infrared light, microwave, sound waves -> can move atoms in molecule but not sufficient. To displace bound electrons

221
Q

What is ionizing radiation

A

Sufficient energy to remove electrons; x rays and gamma rays (dispersed damage; less damage per area), high energy neutrons, alpha particles (damage to restricted area), beta particles

222
Q

What effects does ionizing radiation have

A

Fibrosis, mutagenesis, carcinogenesis, and teratogenesis

223
Q

What are curie, gray, and sievert

A

Curie: amount of radiation emitted by source
Gray: energy absorbed by target
Sievert:

224
Q

What do the effects of radiation depend on

A
  • rate of delivery
  • field size: can sustain high doses when delivered to small fields; smaller doses to large fields can be lethal
  • cell proliferation: rapidly dividing cells more vulnerable; nondividing cells are not killed except at extremely high doses
  • oxygen effects and hypoxia: ROS main mechanism that causes DNA damage; poorly vascularized tissues less sensitive to radiation therapy (ie: center of tumors)
  • vascular damage: endothelial cells moderately sensitive to radiation can cause narrowing of BV leading to impaired healing and fibrosis
225
Q

What is seen in cells that survive radiant energy damage

A

Structural changes in chromosomes that are related to ds DNA breaks; nuclear swelling and condensation and clumping of chromatin; giant cells can persist for years; at high doses, pyknosis and lysis

226
Q

What cytoplasmic changes does radiation cause

A

Cytoplasmic swelling, mitochondrial distortion, degeneration of ER; plasma membrane breaks; *can closely resemble cancer cells which poses problem to pathologist when examining for remaining tumor

227
Q

What are the vascular changes seen in radiation

A

During immediate post radiation, vessels show dilation; with time or higher doses, endothelial cell swelling and vacuolation, necrosis of walls; can rupture or thrombosis; later, endothelial cell proliferation and collagenous hyalinization and thickening of intima -> scarring

228
Q

What effects can radiation have on each of the systems

A
  • Brain: adult -> resistant; embryonic -> destruction of neurons and glial cells
  • Skin: erythema and edema (early); dyspigmentation (wks-months); atrophy, cancer (months to years)
  • lungs: edema, ARDS, interstitial fibrosis (months to years)
  • LN:acute tissue loss, atrophy and fibrosis (late)
  • GI: mucosal injury and ulceration (early); fibrosis of wall (late)
  • Gonads:testis and ovaries destruction (early); atrophy and fibrosis (late)
  • bone marrow: thrombocytopenia, granulocytopenia, anemia, lymphopenia (early)
229
Q

What effect can radiation have on hematopoietic precursors in marrow

A

Cause marrow aplasia; very high doses cause aplastic anemia which is marked by failure of blood count recovery

230
Q

What is the most serious damage to DNA

A

Ds breaks; repaired by homologous recombination and non homologous end joining -> often produces mutation; *also have bystander effect -? Effect behavior of nonirradiated surrounding cells via growth factors and cytokines

231
Q

What is the difference between primary and secondary malnutrition

A

Primary: one or all of components of healthy diet are missing
Secondary:malnutrition results from malabsorption, impaired utilization or storage, excess loss, or increased need for nutrients

232
Q

What are risk factors for PEM

A
  • poverty
  • infections
  • acute and chronic illnesses (ie: HIV) increase metabolic demand
  • chronic alcoholism (thiamine, pyridoxine, folate, and vit A)
  • ignorance of diet supplementation (ie: iron deficiency in infants fed artificial milk)
233
Q

What are the BMI ranges

A

*weight/height
BMI <16 is malnutrition
BMI 18.5-25 is normal

234
Q

How can you measure if someone is malnourished

A

Look at fat sores (thickness of skin folds), muscle mass (reduced circumference of mid-arm), and serum proteins (albumin and transferrin provide measure of adequacy of visceral protein compartment

235
Q

What is marasmus

A

When weight falls to 60% of normal for sex, height, and age; suffers growth retardation and loss of m, resulting from catabolism and depletion of somatic protein compartment (provides body with aa as source of energy); serum albumin are normal or only slightly reduced; production of leptin is low which causes cortisol production and lipolysis; *Extremities emaciated, head too large for body; anemia, immune deficiency

236
Q

What is kwashiorkor

A

Occurs when protein deprivation is more severe than deficit in total calories; *most common in African children who are weaned too early and fed exclusively carb diet; can also occur in chronic diarrheal states b/c not absorbing protein or nephrotic syndrome or after extensive burns; associated with severe depletion of visceral protein compartment and results in hypoalbuminemia which causes edema; subcutaneous and m mass spared; *characteristic skin lesions w/ alternating zones of hyperpigmentation, desquamation and hypopigmentation “flaky paint appearance”; loss of hair color; enlarged fatty liver (reduced synth of carrier protein of lipoproteins); development of apathy, listlessness and loss of appetite; immune defects

237
Q

What are the signs of secondary PEM

A

Depletion of subcutaneous fat in arms, chest wall, shoulders, or metacarpal regions, wasting of quadriceps and deltoid mm, and ankle or sacral edema

238
Q

What happens to the small bowel in kwashiorkor

A

Decrease in mitotic index in crypts of the glands associated with mucosal atrophy and loss of villi and microvilli; loss of SI enzymes most often manifested as disaccharides deficiency; thus, may not respond to full strength milk based diets

239
Q

What happens to the bone marrow in kwashiorkor and marasmus

A

May be hypoplastic b/c of decreased blood cell precursors; red cells can be micro normo or macrocytic

240
Q

What happens to the brains of infants born to malnourished mothers

A

Shown to have cerebral atrophy, reduced number of neurons, and impaired myelinization of white matter

241
Q

Which mediators contribution to cachexia

A
  • proteolytisis inducing factor: glycosyated polypeptide excreted in urine of weight losing patients with pancreatic, breast, colon and o ther cancers
  • lipid-mobilizing factor: increases FA oxidation and proinflammatory cytokines such as TNF and IL-6
  • both of these cause skeletal m breakdown via NFkB activation of ubiquitin protease pathway
242
Q

What are the clinical findings in anorexia

A

Similar to PEM; amenorrhea due to decreased gonadotropin releasing hormone and decreased secretion of LH and FSH, decreased thyroid hormone release leading to cold intolerance, bradycardia, constipation and changes in skin and hair, bone density decreased b/c low estrogen, anemia, lymphopenia, and hypoalbuminemia; *increased susceptibility to cardiac arrhythmia and sudden death resulting from hypokalemia

243
Q

What are the clinical features of bulimia

A

Hypokalemia (cardiac Arrhythmias), pulmonary aspiration of gastric contents, esophageal and gastric rupture

244
Q

What is the difference between fat and water soluble vitamins

A

Fat: more readily stored in body, but may be poorly absorbed in fat malabsorption disorders

245
Q

Which vitamins can be synthesized endogenously

A

Vit D from steroids, vit K and biotin from intestinal micro flora and niacin from tryptophan

246
Q

What are the functions of vitamin A

A

Maintenance of normal vision, regulation of cell growth and differentiation, and regulation of lipid metabolism

247
Q

What is the transport form of vitamin A

A

Retinol; also storage form

248
Q

What are sources of vitamin A

A

Liver, fish, eggs, milk, butter; yellow and leafy green. Vegetables such as carrots, squash and spinach provide carotenoids that can be met to vitamin A

249
Q

What does absorption of vitamin A require

A

Bile, pancreatic enzymes, antioxidant activity in food; stored in liver

250
Q

How is vitamin A taken up by other tissues

A

Retinol binds to retinol binding protein and binds to RBP receptor in peripheral tissues; then binds to cellular RBP and RBP release into blood

251
Q

How is rhodopsin synthesized

A

Oxidation of retinol to all trans retinal, isomerization to 11 cis retinal and covalent association with opsin to form rhodopsin; photon of light isomerizes 11 cis to 11 trans retinol which dissociated from rhodopsin to generate signal

252
Q

How does vitamin A play a role in cell growth and differentiation

A

Play a role in orderly diff of mucus secreting epithelium; when deficient, undergo squamous metaplasia, differentiating into keratinizing epithelium; activation of retinoic acid receptors causes release of corepressors and formation of heterodimers with another retinoic receptor (RXR) -> bind to retinoic acid response element located in reg regions of gens that encode receptors for growth factors, tumor suppressors *all trans retinoic acid has highest affinity for RARs

253
Q

What are the metabolic effects of retinoids

A

RXR binds to 9 cis retinoic acid and can form heterodimers with other receptors such as nuclear receptors involved in drug met, peroxisome proliferator activated receptors (regulators of FA met), and vit D receptors

254
Q

What is the effect of vitamin A on certain infections

A

Can reduce morbidity and mortality of certain diarrhea(restores epithelium in gut); in children with measles, can improve clinical outcome; infections may reduce availability of vit A b/c acute phase response blocks synthesis of retinol binding protein

255
Q

What can vitamin A be used to treat

A

Acne, psoriasis and acute promyelocytic leukemia

256
Q

What can vitamin A deficiency cause

A

Bitot spots, corneal ulcer, keratomalacia (destruction of cornea), metaplasia, kidney stones, night blindness, immune deficiency, xerophthalmia caused by lacrimal epithelium being replaced by keratinized epithelium, hyperplasia and hyperkeratinization of epidermis with plugging of ducts of adnexal glands an produce follicular dermatosis

257
Q

What are the symptoms of acute vitamin A toxicities

A

Headache, dizziness, vomiting, stupor, blurred vision (may be confused with brain tumor -> pseudotumor cerebri)

258
Q

What are the symptoms of chronic vitamin A toxicity

A

Weight loss, anorexia, nausea, vomiting, bone and joint pain; retinoic acid stimulates osteoclasts leading to increased risk of fracture

259
Q

What is the function of vitamin D

A

Maintenance of plasma levels of calcium and phosphorus, bone mineralization, and neuromuscular transmission

260
Q

What is the major source of vitamin D for humans

A

Precursor 7-dehydrocholesterol that requires UV light (UVB) -> cholecalciferol (D3); those with darker skin have lower level of vitamin D production; in plants, registering is the precursor

261
Q

Describe vitamin D metabolism

A

Vit D binds to plasma alpha globulin (DPB) and transports to liver -> conversion to 25 hydroxycholecalciferol in liver through 25 hydroxylase (CYP27A1) -> conversion to 1,25 dihydroxyvitamin D in kidney by 1 alpha hydroxylase

262
Q

How is the production of 1,25 dihydroxyvitamin D regulated

A
  • hypocalcemia stimulates PTH which activates 1 alpha hydroxylase
  • hypophosphatemia activates 1 alpha hydroxylase directly
  • increased levels of 1,25 dihydroxyvitamin D down regulate is own synthesis
263
Q

How does vitamin D function

A

Binds to vitamin D receptor and associated with RXR

264
Q

What are the effects of vitamin D on calcium and phosphorous homeostasis

A
  • stimulation of intestinal calcium absorption in duodenum through interaction of 1,25 dihydroxyvitamin D with nuclear vitamin D receptor and formation of RXR complex -> binds to vit D response elements and activates TRPV6 which encodes calcium transport channel
  • stimulation of calcium reabsorption in kidney in distal tubules through increased expression of TRPV5
  • interaction with PTH in regulation of blood calcium: enhances expression of RANKL (activator of NFkB) on osteoblasts -> binds to preosteoclasts and causes differentiation into osteoclasts -> dissolve bone
  • mineralization of bone: stimulates osteoblasts to synthesize calcium binding osteocalcin involved in deposition of calcium during bone development
265
Q

What happens when hypocalcemia results from vitamin D deficiency

A

PTH is elevated causing activation of 1 alpha hydroxylase (which elevates amount of active vitamin D and calcium absorption), increased resorption of calcium f rom bone by osteoclasts, decreased renal calcium excretion, and increased renal excretion of phosphate (caused by increase in fibroblast growth factor 23 - phosphatonins that block phosphate absorption in intestine and kidney); normal calcium can be restored, but hypophosphatemia will persist, imparting mineralization of bone *FGF23 may be responsible for tumor-induced osteomalacia and hypophosphatemic rickets

266
Q

What levels of vitamin D constitute deficiency

A

< 20 ng/mL

267
Q

What is the sequence that ensues in rickets

A
  • overgrowth of epiphyseal cartilage due to inadequate calcification and failure of cartilage cells to mature
  • persistence of distorted irregular masses of cartilage which project into marrow cavity
  • deposition of osteoid matrix on inadequately mineralized cartilaginous remnants
  • disruption of orderly replacement of cartilage by osteoid matrix with enlargement and lateral expansion of osteocondral junction
  • abnormal overgrowth of cap and fibroblasts
  • deformation of skeleton due to loss of structural rigidity of bones
268
Q

Which bones are most susceptible during different ages in rickets

A

During nonambulatory stage, chest and head -> occipital bones flattened, parietal bones buckle inward by pressure and snap back with release of pressure (craniotabes), frontal bossing and squared appearance of head; rachitic rosary -> metaphysical areas of ribs are subject o pull of resp mm and bend inward creating anterior protrusion of sternum (pigeon breast); during ambulation, affects spine, pelvis, tibia causing lumbar lordosis and bowed legs

269
Q

What occurs with osteomalacia

A

In adults, lack of vit D deranged normal bone remodeling that occurs throughout life; newly formed osteoid matrix is inadequately mineralized producing excess of persistent osteoid (characteristic of osteomalacia); bone is weak and vulnerable to fractures (mostly vertebral body and femoral neck); appears as thickened layer of matrix (stains pink)

270
Q

What are the nonskeletal effects of vit D

A

-macrophages synthesize 1,25 dihydroxyvitamin D via CYP27B in mit; induced by pathogen binding to TLRs

271
Q

What are the consequences of vitamin D toxicity

A

Not from sunlight; oral excess can lead to hypervitaminosis; in children, this causes metastatic calcification of soft tissues (ie: kidney); in adults, causes bone pain and hypercalcemia *potent rodenticide in high doses

272
Q

What can vitamin C deficiency cause

A

Impaired collagen formation which can lead to poor vessel support leading to bleeding tendency, inadequate synthesis of osteoid, and impaired wound healing

273
Q

What is the function of ascorbic acid

A

Accelerates hydroxylation and amidation reactions; activation of prolly and lysyl hydroxylase providing hydroxylation of procollagen ; also has antioxidant properties -> can scavenge free radicals and can regenerate antioxidant form of vit E

274
Q

What can vitamin C excess cause

A

Increased iron overload due to increased absorption, hemolytic anemia in those with G6PD deficiency, and calcium oxalate kidney stones; very rare

275
Q

What is deficiency of vitamin E linked to

A

Spinocerebellar degeneration

276
Q

What are niacin deficiencies linked to

A

3 D’s: diarrhea, dementia, dermatitis

277
Q

What is deficiency of folate linked to

A

Megaloblastic anemia, neural tube defects

278
Q

What is iron deficiency linked to

A

Hypochromic microcytic anemia

279
Q

What is the BMI for overweight and obese

A

Overweight: 25-30
Obese: >30

280
Q

What are the neurohumoral mechanisms that regulate energy balance

A
  • peripheral or afferent system: leptin and adiponectin produced by fat cells, ghrelin from stomach, peptide YY from ileum and colon, and insulin from pancreas
  • arcuate nucleus in hypothalamus: processes and integrates neurohumoral peripheral signals and generates efferent signals; POMC and CART and NPY and AgRP; communicate with second order neurons in hypothalamus
  • efferent system: anabolic and catabolic pathways; control food intake and energy expenditure
281
Q

What does the POMC/CART neurons do

A

Enhance energy expenditure and weight loss by production of anorexigenic MSH and activation of melanocrotin receptors 3 and 4 -> produce TRH and CRH that increase metabolic rate and catabolic metabolism

282
Q

What does the NPY/AgRP neurons do

A

Promote food intake (orexigenic effect) and weight gain via activation of Y1/5 receptors -> release MCH and orexin which stimulate appetite

283
Q

What does a decrease in leptin cause

A

Decreased ability to sense fat stores, overeat and gain weight; leptin secreted when fat stores are abundant *insulin stimulated glucose metabolism is impt factor in regulation of leptin

284
Q

What does leptin do?

A

Stimulates POMC/CART and inhibits NPY/AgRP

285
Q

What do mutations of melanocortin receptor 4 cause

A

Obesity; sensing of anorexigenic signal is not generated and behave as if undernourished; impt downstream signaling of this receptor is brain-derived neurotrophic factor (BDNF) -> haploinsufficiency of this is seen in WAGR syndrome (wilms tumor, anorexia, GU defects, and mental retardation)

286
Q

What does adiponectin do

A

Stimulates FA oxidation in m, causing decrease in fat mass; lower in obese ppl; decreases FA influx to liver, and glucose production in liver, causing increase in insulin sensitivity and protection against met syndrome; binding to receptor triggers cAMP dependent protein kinas A which phosphorylates and inactivates acetyl coenzyme A carboxylase (required for FA synthesis)

287
Q

What does ghrelin do

A

Increases food intake; binds growth hormone secretagogue receptor in hypothalamus and pituitary; stimulates NPY/AgRP; levels rise before meals and fall between 1-2 hours after eating

288
Q

What does PYY do

A

Low during fasting and increase after food intake; reduces energy intake; increase after gastric bypass; decrease with prader willi syndrome

289
Q

What causes the chronic inflammatory state seen in obesity

A

Adipocytes produce cytokines (TNF, IL-6, IL-1, IL-18); high levels of CRP

290
Q

What is metabolic syndrome

A

Visceral or intraabdominal adiposity, insulin resistance, hyperinsulinemia, glucose intolerance, HTN, hypertriglyceridemia, and low HDL cholesterol

291
Q

What can excess insulin lead to

A

Retention of sodium, expansion of blood volume, production of excess norepi and smooth m proliferation = HTN

292
Q

What causes nonalcoholic fatty liver disease

A

Obesity; occurs often in diabetic patients and can progress to fibrosis and cirrhosis

293
Q

What is hypoventilation syndrome

A

Respiratory abnormalities in very obese persons; aka pickwickian syndrome

294
Q

What is hypersomnolence

A

Seen in obese people, AP DIC pauses, polycythemia, and right sided heart failure (cor pulmonale)

295
Q

Which cancers are linked to obesity

A

Esophageal, pancreatic, colon, rectal, breast, endometrial, kidney, thyroid, and GB

296
Q

Describe the mechanisms of obesity causing cancer

A
  • elevated insulin inhibits production of IGF-binding proteins causing a rise in IGF-1 -> mitogen who’s receptor is highly expression in CA; IGF-1 activates RAS and PI3K/AKT which pr Moore growth of normal and neoplastic cells
  • increases synthesis of estrogen through adipose aromatases, increased androgen synthesis in ovaries and adrenals and enhances estrogen availability by inhibiting production of sex hormone binding globulin in liver
297
Q

What are exogenous substances in diet involved in cancer

A

Aflatoxin -> hepatocellular carcinoma (usually with hep B); causes mutation in TP53

298
Q

What do nitrosamines induce

A

Gastric cancer; formed from digested proteins (preservatives)

299
Q

What dietary risk is associated with colon cancer

A

High animal fat intake with low fiber intake

300
Q

What are the leading causes of death in the first year of life

A

Congenital abnormalities, prematurity, SIDS, and low birth rate

301
Q

What are disruptions

A

Results from secondary destruction of organ or body region that was previously Norma in development; arise from extrinsic disturbances in morphogenetic *malformations are intrinsic; ie: amniotic bands

302
Q

What are deformations

A

Also extrinsic disturbance of development; localized on generalized compression of fetus by abnormal biomechanical forces; ie: uterine constraint (Factors that increase risk are first pregnancy, small uterus, bicornuate uterus, leiomyomas, oligohydramnios, multiple fetuses and abnormal fetal presentation); ie: clubfeet -> potter sequence

303
Q

What is a sequence

A

Cascade of anomalies triggered by one initiating aberration; ie: oligohydramnios (potter sequence) -> can be caused by leak in amnion, uteroplacental insufficiency from maternal HTN or severe toxemia, and renal agenesis in fetus; associated with fetal compression -> leads to flattened face, positional abnormalities of hands and feet, hips dislocated, growth of chest wall and lungs compromised (lungs hypoplastic)nodules in amnion (amnion nodosum)

304
Q

What is a malformation syndrome

A

Constellation of congenital anomalies believed to be pathologically related that cannot be explain on basis of single defect; usually caused by viral infection or chromosomal abnormality

305
Q

What is aplasia

A

Absence of organ, but one that occurs due to failure of growth of the existing primordium

306
Q

What is atresia

A

Absence of an opening

307
Q

What does maternal diabetes cause in her unborn child

A

Maternal hyperglycemia induced fetal hyperinsulinemia which causes fetal macrosomia (organomegaly and increased body fat and m mass), cardiac anomalies, neural tube defects and CNS malformations seen in diabetic embryopathy

308
Q

What is the difference between the embryonic period and fetal period

A

Embryonic: first 9 weeks
Fetal: rest of gestation

309
Q

What is valproic acid

A

Antiepileptic that is a teratogen during pregnancy; disrupts express ion of homeobox (HOX) proteins; implicated in patterning of limbs, vertebrae, and craniofacial structures

310
Q

What can deficiency or excess exposure to vitamin A during pregnancy cause

A

Deficiency: malformations of eyes, GU, CV, diaphragm and lungs
Excess: CNS, cardiac and craniofacial defects (cleft lip and palate); later can be derived from retinoic acid mediated deregulation of TGFb signaling which is involved in palate formation

311
Q

What is prematurity defined as

A

< 37 weeks

312
Q

What are the risk factors for prematurity

A
  • preterm premature rupture of placental membranes (PPROM): risks of this occurring are previous preterm delivery, preterm labor or vaginal bleeding during pregnancy, maternal smoking, low SES, poor maternal nutrition
  • intrauterine infection:chorioamniotis (inflammation of placenta), funisitis (inflammation of umbilical cord), malaria nad HIV; TLR -> prostaglandin ->preterm labor
  • twin pregnancy
313
Q

What are the hazards of prematurity for the newborn

A

Neonatal respiratory distress syndrome (hyaline membrane disease), necrotizing enterocolitis, sepsis, intraventricular and germinal matrix hemorrhage

314
Q

What are fetus influences

A

Intrinsically reduce growth potential of fetus despite adequate supply of nutrients; ie: chromosomal disorders, congenital anomalies, congenital infections (should be considered in all cases of FGR) *TORCH group of infections; infants with SGA because of fetal factors usually have symetric growth restriction

315
Q

What placental abnormalities can cause FGR

A

Uteroplacental insufficiency ie: single umbilical a, abnormal cord insertion, placental hemangioma, placental abruption, placenta previa, placental thrombosis and infarction, infection or multiple generations; result in asymmetric restriction (spares brain)

316
Q

What maternal abnormalities can cause FGR

A

Preeclampsia and chronic HTN, thrombophilias, narcotic abuse, alcohol, cigarette smoking, chemo, phenytoin (Dilantin), malnutrition (hypoglycemia)

317
Q

What risks does FGR pose

A

Major handicap, cerebral dysfunction, learning disability, hearing and visual impairment

318
Q

Besides respiratory distress syndrome, what are other causes of respiratory distress in the newborn

A

Sedation of mother, fetal head injury during delivery, aspiration of blood or amniotic flui, intrauterine hypoxia by coiling of umbilical cord around neck

319
Q

What is associated with respiratory distress syndrome of the newborn

A

Male gender, maternal diabetes, delivery by cesarean section; within 30 min, breathing becomes difficult and within few hours, cyanosis and fine rales heard in both lung fields; chest X-ray shows fine ground glass picture (reticulogranular densities)

320
Q

What causes congenital deficiency of surfactant

A

Mutation in SFTPB/C genes

321
Q

When is surfactant production accelerated in the fetus

A

35 weeks

322
Q

Describe what happens in babies born with no surfactant

A

Stiff atelectatic lungs compounded by soft thoracic wall that is pulled in; progressive atelectasis and reduced lung complains lead to uneven perfusion, hypoventilation -> hypoxemia and CO2 retention -> acidosis -> pulm vasoconstriction -> pulm hypoperfusion ->endothelial/epithelial damage -> fibrin rich exudate with formation of hyaline membrane (barriers to gas exchange leading to CO2 retention and hypoxemia)

323
Q

What is surfactant synthesis modulated by

A

Cortisol, insulin, prolactin, thyroxine, TGF beta; *glucocorticoids important -> conditions associated with intrauterine stress and FGR that increase corticosteroid release lower risk of developing RDS; surfactant synthesis can be depressed by high blood levels of insulin in fetuses (diabetic mothers); labor increases surfactant synthesis (reason C section increases risk of RDS)

324
Q

How do lungs of infants with RDS appear

A

Normal size, solid, airless, reddish purple and sink in water; alveoli poorly developed and collapsed; if infant dies early, necrotic cellular debri can be seen in terminal bronchioles and alveolar ducts (incorporated into hyaline membranes made of fibrin and cell debris from type II pneumocytes); *hyaline membranes never seen in stillborn infants; in infants who live > 48 hrs, reparative change are seen (alveolar epithelium proliferates and can detach into airspace where it undergoes phagocytosis)

325
Q

How can you measure the level of surfactant in the fetus while still in utero

A

Amniotic fluid (lung secretions discharged into fluid)

326
Q

What are the complications of high concentration of ventilator administered oxygen for neonates associated with

A
  • retrolental fibroplasia (retinopathy of prematurity)

- bronchopulmonary dysplasia

327
Q

What is retinopathy of prematurity

A

2 phases; 1.) hyperoxic phase: expression of VEGF is decreased causing endothelial apoptosis; VEGF returns to normal after returned to room air (relatively hypoxic), which is phase II -> leads to retinal proliferation characteristic of lesions in retina

328
Q

What is bronchopulmonary dysplasia

A

Decrease in alveolar septation manifested as large simplified alveoli and dysmorphic capillary configuration; caused by reversible impairment in development of alveoli during saccular stage; *hyperoxemis, hyperventilation, prematurity, inflammatory cytokines, and vascular maldevelopment contribute to this

329
Q

What are infants who recover from RDS at risk for

A

Patent ductus arteriosus, intraventricular hemorrhage, necrotizing enterocolitis

330
Q

What is involved in necrotizing enterocolitis

A

PAF -> increases mucosal permeability by promoting enterocye apoptosis and compromising tight junctions; onset of bloody stools, ab distention, and circulatory collapse; ab radiographs demonstrate gas within intestinal wall (pneomatosis intestinalis)

331
Q

What is the morphology of necrotizing enterocolitis

A

Involves terminal ileum, cecum, and right colon; involved segment is distended, friable, and congested; can be gangrenous; intestinal perforation may be seen; coagulative necrosis, bacterial colonization, and submucosal gas bubbles seen microscopically formation of granulation tissue and fibrosis seen after acute episode; can be treated early on but if progressed need resection

332
Q

How are perinatal infections acquired

A

Transcervically (referred to as ascending) or transplaccentally (hematologic)

333
Q

How does the fetus acquire transcervical infections

A

Either by inhaling infected amniotic fluid shortly before birth or by passing. Through infected birth canal; *pneumonia, sepsis and meningitis most common sequelae

334
Q

What are the most common transplacental infections

A

Parasitic and viral; gain access to fetal bloodstream via chorionic villi; can occur during gestation or delivery (hep B and HIV)

335
Q

What are the outcomes of transplacental infections

A

Spontaneous abortion (usually second trimester) stillbirth, hydrops fetalis, or congenital anemia

336
Q

What does parvovirus B19 have tropism for

A

Erythroid cells

337
Q

What do the TORCH group of infections evoke

A

Fever, encephalitis, chorioretinitis, hepatosplenomegaly, pneumonitis, myocarditis, hemolytic anemia, and vesicular or hemorrhagic skin lesions

338
Q

What is early versus late onset perinatal sepsis

A

Early: within first 7 days
Late: 7 days to 3 months

339
Q

What is the cause of early-onset sepsis

A

Group B streptococcus; listeria and candid a -> late onset

340
Q

What is fetal hydrops

A

Accumulation of edema fluid in fetus during intrauterine growth; caused by Rh blood incompatibility (immune hydrops); nonimmune hydrops more common now; hydrops fetalis is generalized edema -> usually lethal

341
Q

What are causes of nonimmune fetal hydrops

A

Turner, trisomy 21 and 18, cystic adenomatoid malformation, diaphragmatic hernia, tachyarrhythimia, high output failure, alpha thalassemia, parvovirus B19, twin to twin transfusion, cytomegalovirus, syphilis, toxoplasmosis

342
Q

What occurs in immune hydrops

A

Abs attach to RBCs -> anemia ->extramedullary hematopoiesis and cardiac decompensation -> hydrops

Abs attach to RBCs-> hemoglobin degredation -> bilirubin -> jaundice and kernicterus

343
Q

What should be administered to Rh- mothers

A

RhIg containing anti-D abs at 28 weeks and within 72 hours of delivery; this is also administered following abortions

344
Q

Why do ABO incompatibilities not have severe effects on fetuses

A

Contain mostly IgM abs and neonatal RBCs express blood group antigens poorly; occurs almost exclusively in. Infants of group A or B born to group O mothers -> firstborn can be affected b/c O mother has IgG abs without prior exposure

345
Q

What are the consequences of excessive destruction of RBCs in neonate

A
  • anemia -> liver and heart hypoxia -> decrease plasma protein synthesis and cardiac decompenation/failure; reduced osmotic pressure and heart failure results in generalized edema and anasarca
  • jaundice -> CNS damage; kernicterus
346
Q

What is the morphology of hydrops associated with fetal anemia

A

Both fetus and placenta are pale; liver and spleen enlarged from cardiac failure and congestion; marrow demonstrates hyperplasia (except in parvovirus infection) and extramedullary hematopoiesis is seen in liver, spleen, and LN; large number of immature red cells (erythroblastosis fetalis)

347
Q

What population is classic PKU seen in

A

Scandinavian

348
Q

Describe the characteristics of PKU

A

Fine at birth, within a few weeks develop rising plasma phenylalanine level which impairs brain development; by 6 months, severe mental retardation; seizures, decreased pigmentation of hair and skin, and eczema often seen

349
Q

What happens to female with PKU who are treated

A

Reach childbearing age and asymptomatic, treatment discontinued; children of these woman have a high likelyhood of being mentally retarded and microcephalic and congenital heart disease *maternal PKU

350
Q

What is the biochemical abnormality in PKU

A

Can’t convert phenylalanine to tyrosine

351
Q

What mutations are seen in classic PKU

A

Complete lack of PAH activity

352
Q

What is benign hyperphenylalaniemia

A

Mutation in PAH that only results in modest elevations of blood phenylalanine levels without Neuro damage

353
Q

Besides a deficiency of PAH, what else can cause PKU

A

Abnormalities in synthesis or recycling of cofactor tetrahydrobiopterin BH4 *impt to recognize because cannot be treated by dietary restriction of phenylalanine

354
Q

What is galactosemia

A

AR disorder resulting from accumulation of galactose-1-P in tissues

355
Q

What are the variants of galactosemia

A
  • total lack of galactose-1-P uridyl transferase (GALT)

- deficiency of galactokinase (rare); milder -> no mental retardation

356
Q

Where does galactose accumulate in galactosemia

A

Liver, spleen, lens of eye, kidneys, heart, cerebral cortex, and RBCs; alternative met pathways activated leading to production of galactitol and galactonate (also accumulate in tissue)

357
Q

What are the clinical features of galactosemia

A

Variable; *liver, eyes and brain most damage; early develop hepatomegaly due to fatty change and can lead to cirrhosis; opacification of lens (cataract) within first few weeksb/c lens absorbs water and swells as galatitol accumulates and increases osmotic pressure, loss of nerve cells, gliosis, and edema in dentate nucleus and olivary nucleus; failure to thrive, vomiting and diarrhea within a few days, jaundice during first week; mental retardation within 6-12 months *not as severe as PKU; aminoaciduria (can’t transport aa in kidney)

358
Q

What infection is sometimes seen in galactosemia patients

A

Escherichia coli septicemia because depressed neutrophil bactericidal activity

359
Q

Even with dietary restrictions, what do people with galactosemia still tend to develop

A

Speech disorder and gonadal failure and sometimes ataxia

360
Q

Describe galactose metabolism

A

Reaction 1: galactose + ATP -> galactose 1-P via galactokinase
Reaction 2: Galactose 1-P + UDP glucose -> UDP galactose + glucose 1-P via galactose 1-P uridyl transferase
Reaction 3: UDP-galactose ->UDP glucose via UDP galactose 4 epimerase

361
Q

What does the polypeptide encoded by CFTR contain

A

Two transmembrane domains, two cytoplasmic nucleotide binding domains (NBDs) and regulatory domain that contains PKA and C phosphorylation sites; two trasnmembrane domains forms channel through which Cl passes

362
Q

How is CFTR channel activated

A

Agonist induced increases in cAMP followed by activation of PKA that phosphorylates the R domain; ATP binding and hydrolysis occurs at NBD and is essential for opening and closing of the channel

363
Q

Which channels does CFTR regulate

A

Outwardly rectified Cl, inwardly rectified K, epithelial sodium (ENaC), gap junction channels, and ATP transport and mucus secretion

364
Q

What is the function of CFTR on ENaC

A

Normal CFTR inhibits ENaC; in CF, ENaC activity increased and increases sodium uptake *except in sweat where ENaC activity decreases -> sine qua non (salty sweat)

365
Q

What is the function of CFTR in diff tissues

A
  • sweat glands: reabsorb luminal Cl and augment sodium reabsorption
  • respiratory: luminal secretion of Cl; mutation leads to isotonic but low-volume surface fluid layer
366
Q

How does CFTR regulate transport of bicarbonate ions

A

Mediated by reciprocal interactions with family of anion exchangers called SLC26 which are co expressed with CFTR; in some mutations, CFTR is preserved but bicarbonate transport is abnormal; alkaline fluids are secreted normally, but acidic fluids are secreted by epithelial harboring mutated CFTR -> leads to increased mucin precipitation, plugging of ducts, increased bacteria binding to mucin *pancreatic insufficiency

367
Q

What is Class I of CF

A

Defective protein synthesis = complete lack of CFTR at apical surface of epithelial cells

368
Q

What is Class II of CF

A

Abnormal protein folding, processing, and trafficking; deletion of delta F 508 is most common; complete lack of CFTR at apical surface

369
Q

What is Class III of CF

A

Defective regulation; prevent activation of CFTR by abrogating ATP binding and hydrolysis; normal amount of CFTR on surface, but its nonfunctional

370
Q

What is Class IV of CF

A

Decreased conductance; mutation in transmembrane domain of CFTR; normal CFTR at apical membrane, but reduced function; associated with milder phenotype

371
Q

What is class V of CF

A

Reduced abundance; mutations affect intrinsic splice sites or CFTR promoter such that there are reduced amount of normal protein; milder phenotype

372
Q

What is class VI of CF

A

Altered function in regulation of ion channels; delta F508

373
Q

What are some examples of modifier genes in CF

A

-mannose binding lectin 2, TGF beta1, interferon related developmental regulator 1; polymorphisms in these genes regulate resistance to lung infections; reason for different pulmonary manifestations

374
Q

What does pseudomonas causes in CF

A

Colonizes lung; concurrent viral infections predispose to colonization; static mucus creates hypoxic micro environment in airway surface fluid which favors production of alginate (mucoid polysaccharide capsule); alginate permits formation of biofilm that protects bacteria from abs and antibiotics producing chronic destructive lung disease

375
Q

Are sweat glands morphologically affected

A

No

376
Q

What can atrophy of exocrine pancreas cause in CF

A

Avitaminosis A can lead to squamous metaplasia of the lining epithelium of ducts in pancreas

377
Q

Describe the liver involvement in CF

A

Bile canaliculi are plugged by mucus material, accompanied by ductular proliferation and portal inflammation; hepatic steatosis, focal biliary cirrhosis

378
Q

What do the salivary glands show in CF

A

Same as pancreas; dilation of ducts, squamous metaplasia and glandular atrophy followed by fibrosis

379
Q

What are the morphological changes seen in CF lungs

A

Bronchioles distended with thick mucus associated with marked hyperplasia and hypertrophy of mucus secreting cells; lung abscesses; *infection with Burkhoderia cepacia is associated with fulminant illness (cepacia syndrome), longer hospital stays and increased mortality

380
Q

How can you confirm CF with individuals who have a normal sweat test

A

Measurement of nasal transepithlial potential difference; with CF< will have more negative potential difference

381
Q

What is SIDS

A

Sudden death of an infant under 1 year of age which remains unexplained after a thorough case investigating, including performance of complete autopsy, examination of death scene, and review of clinical history

382
Q

What is the criteria for diagnosis of CF

A

One or more characteristic phenotypic features or history of CF in sibling or positive newborn screening AND increased sweat chloride concentration or two CF mutations or abnormal epithelial nasal ion transport

383
Q

What is the window of peak susceptibility of SIDS

A

2-4 months

384
Q

What are the parental risk factors associated with SIDS

A

Young maternal age <20, maternal smoking during pregnancy, drug abuse in either parent (specifically paternal marijuana and maternal opiate or cocaine use),short intergestational intervals, late or no prenatal care, low SES, AA or American Indian ethnicity

385
Q

What are the risk factors/postmortem findings associated with SIDS

A

Brain stem abnormalities, usually male sex, prematurity or low birth weight, product of multi birth, SIDS in prior sibling, antecedent resp infections, germline polymorphisms in autonomic nervous system genes

386
Q

What are the environmental risk factors associated with SIDS

A

Prone or side sleep position, sleeping on soft surface, hyperthermia, co-sleeping for first 3 months of life

387
Q

What are the postmortem abnormalities seen in SUID

A

Infections, viral myocarditis, bronchopneumonia, congenital anomaly, congenial aortic stenosis, traumatic child abuse, intentional suffocation, long QT syndrome, FA oxidation disorders, hisiocytoid cardiomyopathy, abnormal inflammatory responsiveness

388
Q

What are things found in infants who died of SIDS

A

Multiple petechiae are most common finding usually on thymus, visceral and parietal pleura, and epicardium; lungs usually congested (represent agonal events; CNS demonstrates astrogliosis of brain stem and cerebellum

389
Q

What classifies as a vulnerable infant to SIDS

A

Delayed development of arousal and cardiorespiratory control ; abnormalities in serotonin dependent signaling

390
Q

What do the laryngeal chemoreceptors have to do with SIDS

A

When stimulates, typically elicits inhibitory cardiorespiratory reflex; stimulation is augmented by resp tract infections which increase volume of secretions and by the prone position, which impairs swallowing and leading of airways

391
Q

What are the two categories of tumor-like lesions

A
  • Heterotopia (choristoma): microscopically normal cells or tissues that are present in abnormal locations; ie: pancreatic tissue in wall of stomach or SI, adrenal cells in kidney, lungs, ovaries; usually of little significantce but can be confused with neoplasms
  • Hamartoma: excessive focal overgrowth of cells and tissues native to organ in which is occurs; do not reproduce normal architecture of surrounding tissue
392
Q

What are the most common neoplasms in children

A

Soft tissue tumors of mesenchymal derivation

393
Q

What are hemangiomas

A

Most common tumors of infancy; can be cavernous and capillary (later is more cellular than in adults, feature that is deceptively worrisome); most are located in skin on face and scalp where they produce flat to elevated irregular red blue masses; some of flat, larger lesions referred to as port-wine stains; may enlarge along with growth but can spontaneously regress; can represent von Hippel-Lindau disease; subset of CNS cav hemangiomas can occur in familial setting -> mutations in cerebral cavernous malformation cornea

394
Q

What are lymphangiomas

A

Characterized by cystic and cavernous spaces; may occur in skin but more often in deep regions of neck, axilla, mediastinum, retroperitoneal tissue; benign but increase in size after birth b.c of fluid accumulation; can encroach on vital structures

395
Q

What is lymphangiectasis

A

Presents as diffuse swelling of part or all of extremity; considerable distortion and deformation can occur; lesion is not progressive; often difficult to correct

396
Q

What fibrous tumors are common in children

A

Fibromatosis or congenital infantile fibrosarcomas (better prognosis than adults); the later has chromosomal translocation t 12;15 (p13;q25) which results in ETV6-NTRK3 fusion *unique to infantile fibrosarcomas; simulates signaling via RAS and PI3K/AKT

397
Q

When is the peak incidence of teratomas

A

Once at 2 years of age and then in late adolescence or early adulthood; first peak is congenital, later may be prenatal origin but are more slow growing

398
Q

What are the most common teratomas of childhood

A

Sacroccygeal; more common in girls; associated with defects in hindgut and cloacal region and other modeling defects; most are mature teratomas; children with malignant lesions tend to be older than 4 months

399
Q

Which neoplasms exhibit sharp peaks in children younger than 10

A

Leukemia (ALL), neuroblastoma, wilms tumor, hepatoblastoma, retinoblastoma, rhabdomyosarcoma, teratoma, Ewing sarcoma, and posterior fossa neoplasms (juvenile astrocytoma, medulloblastoma, and ependymoma)

400
Q

What are neuroblastic tumors

A

Tumors of sympathetic ganglia and adrenal medulla derived from primordial NC cells

401
Q

What are the characteristic features of neuroblastic tumors

A

Spontaneous or therapy induced differentiation of primitive neuro lasts into mature elements, spontaneous tumor regression, and wide range of clinical behavior and prognosis

402
Q

What are the common malignant neoplasms seen in ages 10-14

A

Hepatocellular carcinoma, soft tissue sarcoma, osteogenic sarcoma, thyroid carcinoma, Hodgkin disease

403
Q

Mutations in what gene are implicated in familial predisposition to neuroblastoma

A

Anaplastic lymphoma kinase (ALK); gain of function mutuations in ALK also seen in sporadic form

404
Q

Children diagnosed with neuroblastoma at what age have a better prognosis

A

Younger than 18 months

405
Q

What is the morphology of a transaction neuroblastoma tumor

A

Soft, gray-tan tissue; larger tumors have areas of necrosis, cystic softening and hemorrhage; can sometimes have areas of calcification; histologically composed of small primitive appearing cells with dark nuclei, scant cytoplasm and poorly defined cell borders growing in solid sheets; mitotic activity, karyotype is and pleomorphism; neutropill (fibrillar material) *rosssettes (homer-wright pseudorosettes) can be found in which tumor cells are arranged about a central space filled with neuropil

406
Q

What can be seen with matured neuroblasts

A

*ganglioneuroma; accompanied by appearance of schwann cells -> presence associated with favorable outcome

407
Q

Where does neuroblastoma metastasize

A

Early and widely -> liver, lung, bone marrow, bones

408
Q

What is the staging of neuroblastoma

A

1: localized tumor with complete gross excision with or without microscopic residual disease; ipsilateral nonadherent LN negative for tumor (adherent LN can be positive for tumor)
2A:localized tumor with incomplete gross resection; ipsilateral nonadherent LN negative for tumor
2B:localized tumor with or without complete gross excision; ipsilateral nonadherent LN positive for tumor; enlarged contralateral LN which are negative for tumor
3:Unresectable unilateral tumor infiltrating across middling with or without regional LN involvement or localized unilateral tumor with contralateral LN involvement
4:any primary tumor with dissemination to distant LN, bone, bone marrow, liver, skin or other organs
4S: localized primary tumor with dissemination to skin, live and or bone marrow; *limited to infants younger than 1 year

409
Q

How does neuroblastoma typically present

A

In children under age 2 years with large ab masses, fever, and weight loss; in older children, may not come to attention until mets produce symptoms such as bone pain, resp symptoms, GI complaints; proptosis and ecchymosis may be present due to spread to periorbital region

410
Q

What is blueberry muffin baby

A

Neonates with disseminated neuroblastoma present with multiple cutaneous Mets that cause deep blue discoloration of skin

411
Q

What are the favorable stages of neuroblastoma

A

1,2A,2B,4S

412
Q

What are other indicators of favorable outcome of neuroblastoma

A

Absent chromosome 1 p and 11q loss; present TRKA expression with absent TRKB expression

413
Q

Elevation of what is seen in the urine of neuroblastoma patients

A

Vanillylmandelic acid and homovanillic acid

414
Q

Is HTN common in neuroblastoma

A

No

415
Q

What effect does policy of the tumor cells have on prognosis of neuroblastoma

A

Correlates with outcome in children less than 2, but loses prognostic significant after that; hyper diploid -> better prognosis; near diploid has more genomic instability with complex karyotype; ie:chromothripsis (localized fragmentation of chromosome segment followed by random assembly of fragments; results in amplification of NMYC)

416
Q

What are neurotrophin receptors

A

Marker for neuroblastoma, family of RTKs that regulate growth of neural cells; high expression of TRKA is favorable, TRKB unfavorablle

417
Q

What are therapies used for neuroblastoma

A

Retinoids to induce differentiation of neuroblastoma; targets of ALK mutations

418
Q

What is the peak incidence for wilms tumor

A

2-5 years

419
Q

What is unique about bilateral wilms tumor

A

Onset about 10 months earlier than tumors restricted to one kidney

420
Q

What are risk factors for formation of wilms tumor

A
  • syndromic tumors
  • WAGR syndrome: carry deletions of 11p13; WT1 and deleted AD gene for PAX6 (aniridia)
  • Denys-Drassh syndrome: gonadal dysgenesis (male pseudohermaphrodism), early onset nephropathy leading to renal failure; diffuse mesangial sclerosis; abnormalities in WT1, but abnormality is dominant negative missense mutation in zinc-finger region of WT1 that affects its DNA binding ability -> GU ab but no tumor; increased risk for gonadoblastomas
  • Beckwith-Wiedemann syndrome: organomegaly, macroglossia, hemihypertrophy, omphalocele, ab large cells in adrenal cortex; *genomic imprinting WT2; IGF2 expressed from paternal allele -> loss of imprinting; also at risk for hepatoblastoma, pancreatoblastoma, adrenocortical tumors, and rhabdomyosarcomas
421
Q

What are nephrogenic rests

A

Putative precursor lesions of wilms tumor; seen in renal parenchyma adjacent to some unilateral tumors and all bilateral tumors; *impt to identify because then at increased risk for developing tumor in contralateral kidney

422
Q

What is the morphology of wilms tumor

A

Well circumscribed, soft, tan to gray, coco hemorrhage, cyst formation, necrosis; *triphasic combo of blastemal, stromal, and epithelial cells observed in majority of lesions; presence of anaplasia correlates with TP53 mutation and resistance to chemo

423
Q

What are the clinical features of wilms tumor

A

Large ab mass that can be unilateral or extend across middling and down into pelvis; hematuria, pain in abdomen, intestinal obstruction, HTN; pulm met often present at time of primary diagnosis; most patients can expect to be cured

424
Q

What correlates with adverse prognosis in wilms tumor

A

Anaplasia, loss of genetic material on chromosomes 11q and 16q, gain of chromosome 1q

425
Q

What are individuals with wilms tumor at risk for

A

Developing second primary tumors including bone and soft tissue sarcomas, leukemia, lymphomas, and breast cancers; usually from radiation treatment

MOD II (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions