Complications and Etiology Flashcards
1
Q
CLL/SLL
A
- Recurrent infections (S. pneumoniae, due to neutropenia and hypoglobulinemia - Indolent, incurable -transforms to DCBL - transform to AML Evans syndrome–> CLL+H.pylori+ITP
2
Q
Cancers that transform DLBL
A
-CLL/SLL -Follicular Lymphoma
3
Q
Hairy Cell Leukemia
A
- Recurrent infections (common COD) - CHF Death due to anemia
4
Q
Multiple Myeloma
A
-Recurrent infections (d/t neutropenia, and monoclonal Ig=lacks antigenic diversity) - Renal Failure (4 reasons): 1) AL amyloidosis 2) increased uric acid–>toxic to kidney tubules 3) increased serum calcium- stones and toxic 4) acute pyelonephiritis due to recurrent Kidney infections - hyperviscosity similar to waldenstrom - systemic amyloidosis restrictive cardiomyopathy Pathological bone fractures due to Lytic lesions
5
Q
Osteoperosis
Complications
A
- Pathological fractures–> DVT d/t immobility–> Pulmonary Embolus. (Most common COD) - Orthostatic Pneumonia
- loss of height d/t compression fractures
- Hip fractures (most common site)
- Secondary OP Hyperparathyroidism, vit D or C def***, corticosteroids
6
Q
Hyperparathyroidism
A
Pathological fractures d/t osteopenia Hypercalcemia: -arrythmias (most common COD) -acute pancreatitis (calcium activates pancreatic enzymes) -Kidney stones -nephrogenic diabetes insipidus and acute renal failure
7
Q
Osteomalacia/Rickets
A
Pathological fractures–>DVT–>Pulmonary embolus
8
Q
Scurvy
A
Fragile capilaries; venules–> subperiosteal hemorrhages defective osteoid synthesis–> microfractures Bony deformities
9
Q
Pagets Disease (disease of osteocclasts)
A
Etiology: paramyxo virus (measles, RSV)–>IL6, p62 mutation) 3 stages: osteolytic, mixed, osteosclerotic comp: -pathological “Chalk stick Fracture” due to bowing of tibia–>pain -deformities–>pain (compressed nerves especially CNVIII) -degenerative joint disease–>pain Rare: -High output congestive heart failure due to increased angiogenesis involving osteoblast activity–>increased AV shunt (volume overload) -commonly leads to osteosarcoma -can lead to osteoclastoma
10
Q
Alport
A
Et: type IV collagen defect, x-linked Comp: progresses to FSGS, loss of hearing and vision
11
Q
Osteogenesis imperfecta (abnormal matrix production)
A
Et: Type 2 (collagen type 1&2 defect) -incompatible with life, in utero microfractures Type 1 (collagen type 1) -blue sclera comp: Pathological bone fractures increasing in intensity with age.
12
Q
Ehlers Danlos
A
et: collagen type III (reticulin)-blood vessels.. comp: aortic dissection, osteopenic bone–>Kyphoscoliosis, spondolisthesis
13
Q
Marfan’s
A
et: Fibrillin gene chromosome 15 comp: Aortic dissection, Mitral valve prolapse, aortic dilatation due to cystic medial necrosis, - eyes: subluxation of the lens-ectopia lentis
14
Q
Osteopetrosis (osteoclastic failure) -abnormal modeling/remodeling
A
Et: Genetic mutation in Carbonic Anhydrase II Gene, Rank ligand gene or chloride channel gene Comp: Recurrent infections*, pathological fractures, extramedullary hematopoiesis–>hepatosplenomegaly, Compression of CN VII&VIII, Normochromic normocytic anemia–>COD*
15
Q
Achondroplasia
A
et: FGFR3 mutation, gain of function AD
16
Q
Osteomyelitis
A
Et: S. aureus (most common COD), GU infections (UTI, cystititis), IVDA: E. coli, Lkebsiella, Pseudomonas - direct inoculation mixed bacteria -Neonates: H. influenza, Group B streptococcus - Sickle cell anemia= salmonella comp: - extension into joint space= acute septic arthritis -Chronic osteomyelitis: Brodie abscess- intracortical abscess Sclerosing OM of Garre at the jaw= extensive new bone obscuring the underlying bone Secondary amyloidosis Squamous cell carcinoma of fistula
17
Q
Potts disease
A
et: hematogenous spread of tuberculosis comp: psoas abscess- cold abscess d/t minimal inflammatory response/no spiking fevers seen in the normal abscesses - myelophisic- metastasis to the bone–>caseating granulomas replacing normal bone marrow–> inadequate cell formation -amyloid deposition (eosinophilic glassy materila) in the kidney - Kyphosis & scoliosis -compression of spinal nerves
18
Q
Osteoarthritis -non-inflammatory*
A
ET: age, recurrent trauma, obesity Comp: Joint mice - osteophytes in spine (spinal nerve compression) - following knee or hip surgery–>septic arthritis (most common cod)
19
Q
Rheumatoid
A
ET: HLA DRB1, coexists with autoimmune conditions (mostly Primary biliary cirrhosis) Comp: -AA amyloidosis (systemic)–> Nephrotic syndrome–>anarsaca and restrictive cardiomyopathy in heart–>arrythmias -Atheroslerotic plaques–>MI in adults (most common COD) - recurrent infections–>most common in kids - Episcleritis - Rupture of Baker’s cyst–> mimics DVT - Ulnar deviation of fingers - Swan neck deformity- flexion of DIP & hyperextension of PIP - Boutouneire’s- Hyper extension of DIP and flexion of PIP Rheumatoid nodules**–>central fibrinoid necrosis surrounded by histiocytes & chronic inflmmamtion cells - fibrous ankylosis=fusion of the joints -subluxation of C1-C2 (Atlanto-axis joint) - carpal tunnel syndrome - Lung involvement- pleural effusions and end stage lung disease Acute necrotozing Vasculitis: -heart–>MI -Brain—>cerebrovascular occlusion -Kidneys–> renal failure - Mesentery –> red infarction in GI/mesenteric ischemia - Gangrene of digits Chronic analgesic abuse–> ureteric obstruction–> bilateral necrosis of renal papillae
20
Q
Osteioid Osteoma
A
ET: tumor of younger males Complications: appendicular skeleton - nocturnal pain relieved by ASA
21
Q
Osteoma
A
ET: benign tumor of mature bone, craniofacial bones Ass: Gardners syndrome=FAP + multiple osteomas, desmoid tumor and epidermal cysts
22
Q
Osteosarcoma (tumor of osteoblasts)
A
ET: primary-mutation in p53, MDM2 (inactivates apoptotic capacity of p53) and RB, secondary: pagets disease - metaphyseal long bones in kids, flat bones in elderly-bimodal Comp: hematogenous spread, hemoptysis, chest pain and breathlessness.
23
Q
Osteochrondroma
A
Et: displaced fragments of the growth plate, clonal proliferation (neoplasm), EXT gene family mutations -only in bones with endochondral ossifications Comp:
24
Q
Echondroma - “benign tumor of cartilage (hyaline & myxoid) originating from metaphyses”. -“O ring sign on X-ray”
A
Et: 20-40 year olds -Olliers: multiple enchondromas on one side of the body–>increased risk of chondrsarcoma (20%)–>disfiguring -Mafucci: 20% chance chondrosarcoma/ 100% chance soft tissue angiomas, CNS gliomas & ovarian carcinomas COMP: bone pain and pathological fractures
25
Chondrosarcoma
Et: 30-60yrs, can follow olliers or mafucci from metaphysis but majority arise sporadically from epiphysis -axial skeleton Comp: -Bone pain, pathological fractures -High invasive--\>metastasis to lungs--\>hemoptysis
26
Osteoclastoma (Giant Cell tumor)
Et: 20-40yrs, pagets, benign tumor of mesenchyme Comp: Pathological fractures, can metastasize to lungs via blood, high RECURRENCE after surgery.
27
Ewing's Sarcoma
Et: Primitive Neuroectodermal tumor (PNET) - t(11:22) or t(21:22) translocation Prognosis: dismal but improves with chemo -In 99% of people with Multiple Myeloma
28
Fibrocystic Change ("Lumpy Bumpy Breast")
Et: Exagerated response to Estrogen occuring at the terminal duct lobular unit
age: 35-40
- oral contraceptives reduce risk of FCC
two types:
* simple/ non-proliferative- no malignant potential
* Prolifertive: epithelial hyperplasia--\>increased malignant pot.
29
Duct ectasia (aka Plasma cell mastitis, granulomatous mastitis)
Et: dilated duct raptures--\> inflammation, plasma cells, histiocytes, giant cells, granulomas
mimics carcinoma clinically (so does Traumatic fat necrosis)
30
Fibroadenoma
Et: not caused by estrogen!!
- most common benign tumor of the breast ("breast mouse")
- Neoplastic cells in the intralobular stroma
- unilateral in women of reproductuve age
comp: No malgnancy
- Pericanalicular
- Intracanaloicular
31
Phylolloides Tumor (Cystosarcoma phylloides)
Et: Intralobular stroma (periductal)
- post menopausal women (\>50yrs) with unilater pendulous breast
comp: beningn, borderline or malignan
- hematogenous spread (no lymphadenopathy)-Lungs first (LLBoneBrainK)
32
Intraductal Papilloma
ET: lacteriferous ducts, (35-55)
--common cause of muco discharge in young women
- no inflammation becausd no infection
- myoepithelial cells are the Gate keepers
Comp:
* The more INtrductal papilloma the higher the risk of cancer--\>papilllomatosis--\>Papillary carcinoma of the breast \*
* Invasion of the fibrovascular core d/t absencer of myoepithelial cells & most commonly seen in post-menopausal women
33
Breast Cancer
Pre disposing factors: female, increased age, BRCA, Her2Neu, p53, obesity (d/t increased estrogen), early menarche & late menopause, family history, race/ethnicity, ERT, granulosa theca ovarian tumor (d/t increased estrogen)
origin: termonal duct lobular unit
- elderly women=age
- middle-age women=family history & then nulliparity
34
Comedo
Et: intraduct tumor (high greade DCIS)
- necrotic center (toothpaste)
comp: high recurrence rate , upto 60% become invasive.
35
Invasive Duct Ca
Et: commonest (75%)
sciirhous- hard, dense, desmoplasia (cords and nests of cells) 3-4cm
-necrosis, calcifications
36
Other Carcinomas of the Breast
**Mucinous (colloid) Ca.**
-good prog. associaed with solid/non-invasive papillary Ca.
**Medullary Carcinoma** - (dysgerminma of ovaries and seminoma of testes-fried egg appearnce)
- No outer myoepithelai layer, chemo works
- fleshy, soft
**Infllammatory carcinoma** (african american womne)
-poor prognosis
37
Simple (non-neoplastic) cyst
- Follicular
- Corpus Luteal cyst
Follicular
Et: increased estrogen-lined by granulosa cells
-seen with PCOD
Corpus Luteal cyst
-Et increased progesterone
seen in type 2 diabetes
Comp: rapture, torsion, no malignancy
present likr appendicitis
yersinia enterocolitis can mimic
38
Chocolate cysts of the Ovary
Et: endometriosis (repeated cyclical hemorrhage)--\>induce fibrosis, adhesions, severe oain
Complication:
Clear cell Adenocarcoma (uncommon)- associated with endometriosis; agressive
Infertility (d/t tubal scars)
regression following oral contraceptives
39
Polycystic Kidney disease
Comp: **diabetes, infertility**, increased estrogen (fibrocystic change in breast and endometrial hyperplasia/casrcinoma), fibroadenoma/leiomyoma grow bigger
TXT: Clomiphine-induce ovulation
metformin-Diabeter melitis (increases insulin sensitivity), Birthcontrol-regulate menstrual cycle, spirinolactone- hirsutism
\>3 LH:FSH
40
Serous Ovarian tumor (most common ovarian tumor)
-surface epithelial tumor-
Et: Looks like fallopian tube
Benign, Borderline and Malignant (low grade-KRAS, BRAF-high grad-p53, BRCA)
(unilocular), papillary projections & psammoma bodies
41
Mucinous Ovarian Tumor
surface epithelial tumor
Et: look like endocervix/intestine
No papillae or PSaMMoma
Comp: "Jelly Belly"/pseudomyxoma peritonei--\>in borderline and malingnant stage
* Most common cause = adenocarcinoma of the appendix
42
Endometroid Tumors
surface epithelial tumors
Et: PTEN, KRAS, Beta-catenin, MSI
- solid & cystic, velvety surface
- resembles endometrial Ca-Not normal endometrium (as seen in endometriosis)
43
Brenner's tumor -surface epithelial tumors-
ET: like transitional epithelium
- spindle cells with nests of urothelium
- solid but bening
Complication: Torsion No rupture b/c solid tumors dont rapture
4Bs: Brenner, Benign, coffee Bean nucleus, Bladder like epithellum
44
Mature Cystic Teratoma/Dernoid Cyst
Et: germ cells
Comp: rupture, torsion, infertility, transformation to **invasive squamous cell carcinoma**
commonly on the right
45
Immature Teratoma (Malignant teratoma)
-germ cell-
Seen in young women (18 years)
- presense of neuroepithelium--\>malignancy
comp: Bulky, solid, hemorrhage, necrosis
46
Specialized Teratoma
-Germ cell-
Struma Ovarii;
et: germ cell
PG: thyrotoxicosis d/t T3/T4 production
comp: suppresses TSH--\> thyroid Atrophy
Cacrinoid Tumor:
- Carcinoid syndrome (increased serotonin)
- Neuroendocrine origin= salt & pepper appearance
comp: episodic flucshing, wheezing & diarreahea
Both are asymptomatic b/c rarely functional
Struma Carcinoid: combined
47
Endodermal Sinus Tumor (Yolk Sac)
-germ cell-
Et: children & younger woman, derived from yolk sac
tumor marker=AFP & Alpha 1 antityrypsin
Schiller-Duval bodies: layers of epithelial cells around blood vessels-resemble glomeruli
48
Dysgerminoma (oocytes)
-germ cell tumor-
Et: unilateral solid mass & malignant-seen in TURNER'S PATIENTS d/t gonadal dysgenesis
lymphocytic infiltration,
Cured by, surgery, radiosensitivity
marker: LDH due to syncytiotrophoblasts
unilateral solid tumor
comp: torsion
49
Ovarian Choriocarcinoma
(Non-Gestational)-germ cell-
Et: young girls (\<18years) with amenorreah & exaggerated morning sickness d/t increased B-hCG
-malignant cytotrphoblasts and syncytiotrophoblasts secreting B-hCG (usually only Syn. scretes)
Marker B-hCG, no chorionic Villi
hematogenous spread not lymph (LLBBK)
complication: bad prog. unresponsive to chemo because no paternal Antigens (which are found only in gestational choriocarcinoma)
- note dont confuse hsitology with osteoclastoma
50
Granulosa Theca Cell tumor
-sex cord tumor-
et: predominantly in post menopausal women
- increased ESTROGEN
marker: **tissue inhibin (inhibits FSH**)
- **Call-Exner bodies**=cuboidal granulosa cells arranged around a central lumen
**Comp:** metastasis, follicular cysts in other ovary, increased estrogen (breast cancer, FCC, endometrial carcinoma, enlargment of leiomyoma/fibroadenoma, precocious puberty)
51
Fibrothecoma
-sex cord-
benign
pure fibroma + right sided pleural effusion + ascites= Meig's syndrome & basal cell nevus syndrome/Ghorlin syndrome
comp: torsion
52
SERTOLI-LEYDIG CELL TUMOR (**androblastoma**)
Et: **20-30yrs**
**Reinke crystals**
comp: defeminization, Masculinization
53
Krukenberg Tumor
Et: secondary ovarian tumor d/t meatstasis to both ovaries
3 different sites of sites: diffuse gastric carcinoma (linitis plastica\>Colon cancer\> Invasive lobular carcinoma of the breast
PAS +ve, always Bilateral, CEA
-**all 3 tumors have E-cadherin mutations**
comp:
54
Chocolate cysts
Et: endometriosis-repeated cyclical hemmorhage
COMP: infertility, Pain
55
Endometrial Hyperplasia
Simple (with/without atypia)= less glands
complex (with/without) atypia= more glands
ET: unopposed estrogen
* Obesity, granulosa theca cell tumor, menopause, type 2 diabetes, metabolic syndrome, tamoxifen, ERT, PCOS, zona reticularis (produces androgens) of adrenal cortex, **PTEN**.
Comp: Endometrial carcinoma if atypia is present
56
Endometrial
Et: 55-65 yrs, unopposed estrogen in post or peri-menopausal women
**obesity**, granulosa theca cell tumor, menopause type 3 diabetes, metabolic syndrome,tamoxifen, ERT, PCOS, zona reticularis (produces androgens) of adrenal glands
Precursor lesion: endometrial hyperplasia **WITH ATypia**
Endometioid (type 1): indolent
* -Peri-menopausal women
* -PTEN mutation
* -Glands on histology
* **Endmetrial hyperplasia**
Serous (type 2): aggressive
* Elderly women (post-menopausal)
* p53 mutation
* papillary with psmmoma bodies
* **endometrial atrophy**
COMP: spread to cervic, vagina, liver, lung, brain & bone via LYMPH
57
Malignant Mixed Mullerian Tumor (mixed mesodermal tumor/ carcinosarcoma)
Et: \> 55 years women
comp: poor prognosis, high grade
58
Uterine fibroids/Leiomyoma
Et: Unknown
common in nulliparous African American women
59
Hydrocephalus
Path:
communicating-all ventricles dilate
* Normal pressure: dementia, ataxia & urinary incontinence
* Pseudomotor cerebr (benign intracranila HTN)- females, obese, headaches & vision loss
Non-communicating- obstruction (usually by tumor) b/w the lateral & 3rd ventricle or b/w 3rd &4th
hydrocephalus ex vacuo
COMPs:
* cushings's reflex- triad indicating an impending herniation-elevated systolic pressure (wide pulse pressure), Bradycardia, irredular repsirations,
* Tonsillar herniation (through foramen magnum- immediate death) or trans-tentorial/uncal herniation (--\>ipsilateral pupillary dilation d/t compression of CN III)
60
Epidural Hematoma
Et: temporal side of the head--\>fractured pterion--\>middle meningeal artery
lucid interval--\>talk & die
Comps:
Uncal herniation [small flame shaped hemorrhages in the pons on autopsy]
61
Subdural Hematoma
Et: Rapture of bridging veins; recurrent falls in elderly--\>stretch veins--\>rupture; alcoholism--\>cerebral atrophy; Shaken baby syndrome d/t thin walls of veins
Comp: Uncal herniation
62
Cerebrovascular disease
Infarct:
-loss of adequate blood supply. Thrombosis or Emboilzation
Hemorrhage;
* Intraparenchymal: Hypertensive (basal ganglia, brainstem, cerebellum); other (often lobar-example amyloidosis), arterial venous
* subarahnoid: usually from aneurysm rupture
63
Intraparenchymal/ Intracerebral Hemorrhage
Et:
* Long standin benign HTN--\> hyaline artiosclerosis
* Non-hypertensive hemorrhages\*\*: arerial-venous malformation; Cerebral amyloid angiopathy + HTN
* Cocaine
Comp: Herniation & death
64
Subarachnoid Hemorrhage
Et: Berry aneurysm
Associated ih Marfan's, Ehler's Danlos, ADPKD
comp:
Ischemic stroke from cerebral vasospasms
comminicating hydrocephalus
65
* hydrocephalus
Pa:
* Communicating
* Normal Pressure: Dementia, ataxia, urinary incontinence (respond to LP/shunt)
* Pseudomotor cerebri (benign intracranial HTN): female, obese, headaches & vision loss
* Non communicating: blockage between 3rd & 4th ventricle--\>dilatation of ventricles proximal to the obstruction- Most common location: foramen of Monro
* Hydrocephalus ex vacuo- dilation of all ventricles due to cerebral atrophy (alzheimers, Niemann Pick)--\>compensaory increase in CSF
COmp:
* Cushings reflex: triad indicating an impending herniation:
1. Elevated systolci pressure (eide pulse pressure)
2. Bradycardia
3. irredular respirations
* Tonsilar herniation
;
66
Epidural Hematoma
Comp: Uncal herniation
67
Subdural Hematoma
Et: Rupture of Bridging veins (low pressure so gradual onset)
* Recurrent falls in elderly
* alcoholism
* shaken baby syndrome d/t thin walls of veins
COMP: Uncal herniation
68
Coup/contre-coup contusions
* CSF cushion
* Bony ridges
* Stationary head
* accelerating head
69
Diffuse Axonal Injury (DAI)
* Rotational acceleration
* Shearing of axons as they are stretched beyond elastic point with roatational force
* No Lucid interval-unplugged
70
Concussions
transient and highly variable disturbance of neurological function following trauma
* Blow to the head is not required
* predispostions: APO-E genotype, other..
* Repeated insults (boxing, football, hockey..) may increase risk for neurdegenerative disease
* Theories:microscopic membrane injuries, disruption of BBB, convulsive
* key to detection of subtle injury? Baseline data
71
Cerebral infarct
Et:
* **Thrombotic/ischemic stroke**=HTN--\>thrombosis--\>bland infarct
* **Embolic stroke=** atrial fibrillation + mural thrombus in left heart--\> legs (DVT)-legs most common- or brain (red infarct)
* **Carotid artery dissection** (young-middle aged)-mild trauma--\>occludes lumen & causes stroke (extension to adventitia causes subarachnoid hemorrhage
COMP:
* Contralateral hemiparesis & sensory loss
* affecys cerebellum (D-DANISH)-dysarthria, dysdiadochokinesia, dysmetria, Nystagmus, intention tremor, Slurred speech, Hypotonia
* affects Broca's area--\> aphasia
72
Intraparenchymal/Intracerebral Hemorrhage
ET:
* Long standing benign HTN--\>hyaline arterioslerosis (bland "Lacunes")
* Malignant HTN--\>direct rupture of arteries (w/out aerteriosclerosis)
* Non-hypertensive hemorrhages:
* Arterio-venous malformation- greatest pnot form hemorrhage (3-4th decade)
* Cavernous hemangiomas, capillary telangiectasiasis
* Cerebral hemorrhage angiopathy + HTN--\>hemorrhage in basal ganglia
* **COCIAINE!!**
Comp:
Longstanding HTN--\>hyaline arteriosclerosis of lenticulostriate arteries--\> **Charcot Bouchard Aneurysm (slit hemorrhages)**
* herniation & death (more common than ishemic stroke)
73
Subarachnoid Hemorrhage
Et:
* Berry aneurysm (born with malformation in the IEL of media of the vessels, Not a berry aneurysm)
* other aneurysms: **Giant fusiform** (Basilar artery); **Mycotic aneurysom**M: healed arteritis after emboliztion of infected thrombus (endocarditis); Traumatic & dissection
* Associated with Marfan's, Ehler's Danlos, AD Polycystic Kidney disease
Comp:
* ischemcic stroke from cerebral vasospasms
* communicating hydrocephalus
* mimics meningitis
74
Brain Abscess
Et: Two routes of spread: Hematogenous (septic emboli or sepsis); Contigual/direct spread 9sinusitis, mastoiditis, otitis media& dental infections
Comp: Rupture into venticles--\>ventriculitis--\>obstruction of ventricles--\>hydrocephalus
75
Alzheimers
Et: -Occipital lobe is spared-
* starts in temporal (hippocampus)--\>frontal & parietal
80% sporadic-age
20% are hereditary
* Downsyndrome (APP is on Ch 21)
* Early onset AD:
* APP (ch21), presenillin (ch1 & 14), chlustering (ch 8) & complement receptor-1 (ch 1)
* Late onset AD:
* Apo E genotype (ch 19)
* ApoE4-increases the risk of AD
* ApoE2-decreases the risk of AD
COMP:
* Most commn cause of death- Aspiration pneumonia
* Hydrocephalus Ex Vacuo
* Bed sore/pressure sores & DVTs--\> pulmonary embolus (can lead to lung abscesses involved with AA amyloid)
* Cerebral amyloid agiopathy--\> lobar hemorrhages (no history of HTN)
* deposition of amyloid (homogeneous eosinophilic materla) in the walls of cerebral vessels
76
Parkinson's
triad: tremor, rigidity, akinesia
Et: Most cases sporadic; mutation in the synuclein gene (a component of Lewy bodies)
* Non- degenerative causes= medication, cocaine abuse
* atrophy of Substantia Nigra & presence of lewy bodies
77
Huntingtons
Et: CAG repeats with genetic anticipation--\>gain of function mutation
AD-males=females
Caudate and Putamen atroph
less atrophy of GP or cerebral cortex
78
ALS/Lou Gehrig's disease/ Motor Neuron Disease
Et: affects middle-aged
* Mutations: Ch9 hexanucleotide repeat (C9ORF72)
* SOD-1
* Pathogenesis:
* Neuronal loss in spina cord ant. horns (motor cortex)
* -intelletc, sensatio, sphincter control and eye movemnts spared
* life expectancy 2-5years (10% hereditary)
* cytoplasmic inclusions:
* Ubiquitin (a protein deposited in response to cell injury)
* TDP-43, FUS (DNA/RNA binding/stabilizing proteins)55
79
Multiple sclerosis
Et:
* multifactorial, prevalent in temperate climate (caucasian female in temperate climate)
* Autoimmune HLA-DR2 & DR15--\>ABs destroying oligodendrocytes
* Other **risk factors**: smoking, low vitamin D, EBV, maternal history & move to endemic area before puberty
* Commonly affects CNII--\>optic neuritis--\>pain on eye movement, blurred vision and diplopia
* destruction of MLF--\>internuclear ophthalmoplegia--\> ipsilateral eye cannot adduct while contralateral eye undergoes nystagmus
* Argyll Robertson syndrome-bilateral small pupils
* cerebellum, brainstem & spinal cord can be afeccted
* Bladder--\>stasis--\>UTI
80
Post-infection demyelination
Et:
* Following flu like illness
* Occasionally following vaccination
* Acute inflammatory encephalopathy
* with AHEM or, without (ADEM) hemmorhage
81
Myelinloysis
Central pontine myelinolysis
Extra-pontine myelunolysis:
* pathogenesis: unknown
* renal or hepatic disease
* severe
* congestive heart failure
* SIADH
82
Wernicke's Encephalopathy
Et:
* Thiamine def:
* Encephalopathy, confusion
* ocular palsies
* ataxia
* korsakoff's psychosis: no new memories
* Key Targets:
* Mamillary bodies, thalamus, periaqueductal gray matter
83
Oligodendroglioma
3rd-4th decade
indolent course and often calcified
Et: Loss of hterozygosity for ch1 and ch19
God prognosis becaus chemosensitive!
-better prognosis if 1p and/or 19q deletions
84
Pilocytic Astrocytoma
Most common primary CNS tumor in childhood
well-differentiated glioma in the cerebellum & hypothalamus
* composed of compactly & loosely arranged delicate hair like astrocytes
* CT/MRI: c ystic with enhancing rim & mural nodule
* cured by resection
85
Glioblastoma Multiformes
Older patients
high grade astrocytoma
Tumor marker GFAP (glial fibrillary Acidic protein)
poor prognosis: infiltrate, unresectable & resistant to treatment
Better prognosis: younger, -EGFR, + IGH, + p53, + MGMT methylation
86
medulloblastoma
Et: arises from vermis of cerebellum and can co-exist with ewing sarcoma
homer-wright rosettes (pseudorosettesz)
cerebellar signs (D-DANISH)
complications :
* Malgnant tumor--\>CSF spread--\>ventricles--\>hydrocephalus
* Drop metastasis
87
Sarcoma Botryyoides (Embryonal Rhabdomyosarcoma)
girls\<5years old
"bunch of grapes"-polypoid friable mass hangning in vagina
**HIGHLY MALIGNANT, malignant rhabdomyoblasts, cambium layer, fibromyxomatous stroma**
**Require surgery + chemotherapy**
**Histology: rhabdomyoblasts (precursors of skeletal muscle)**
88
Partial Mole
2 sperms 1 normal ovum
69 chromosomes (69, XXY)
fetl tissue present
some villi ae hydropic
focal trophblastcic proliferation
COMP: Bilateral theca Lutein cysts
89
Complete Mole
Empty ovum + 2 sperm
56 chromosomes (46XX or 46 XY)
Fetal tissue absent
most vilii are hydropic
fDiffuse trophoblastic proliferation
COMP:
* Bilateral theca lutein cysts due to B-hCG
* invasion of myometrium
* gestational choriocarcinoma (goes unto endometrial cavity)
90
Vulvul Intraepithelial Neoplasia (VIN)
Risk factors: HPV, 16, 18, 31, 33, (45)
40years
smoking
immunosuppressed
50-60% have syynchronous lesions in the cervix, vagina, urethra, anus
35-59% recur after local treatment
VIN III: Bowen's disease (carcinoma in situ)
* Leukoplakia
* or reddish brown plaque
* needs surgical excision
91
Carcinoma vulva
\>60 years
plaque, nodule, ulcer
anterior 2/3 of labia majora
squamous cell carcinoma (usuall invasive on labia minora)
Inguina and pelvbic node
92
acute Tubular necrosis
Et: ischemic & toxic
3 phases:
1. Initiation phase (36 hours):
* acute decrease in GFR & rapid increase in serum Cr & BUN
2. Maintenance phase
* plateau of BUN and Cr
3. Recovery phase
COMP:
* Ischemic insult--\> hypotension, vasodilatory (septic shock), systemic infection, hemorrhage shock (GI bleeing), hypovolemic shock (vomiting, diarreah)
* Nephrotoxic:
* Exogenous= aminoglycosies
* Endogenous=hemoglobinuria & myoglobniura
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Acute pyelonephritis
Et: E. coli (most common cause)
ascending infection or hematogenous spread
* seeding of kidney from sepsis or endocarditis
* symptoms of cystitis: increased urinary frequency, urgency , dysuria & suprapubic pain
complications
3P's: pyonephrosis, papillary necrosis & perinephric abscess
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Papillary Necrosis
Et:
* chronic anlagesic abuse (ASA (arpiri/NSAIDs), caffeine, acteminophen, codeine
Pa:direct toxic effects=acetminophen
Ischemic effect= ASA
--\>causes chronic tubulointerstitial nephritis
Intravenous pyelogram (IVP): ring defect at the tips of minor calyces
* Papillary necrosis pyelonephritis:
* Pa: interstitial inflammation compress medullary vasculature--. ischemic 7 paillary necrosis
* treat underlying infection
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renal stones
ET: Men\>women (20-30yrs old)
types: Calcium oxalate/phosphate (75%), struvite-Mg/ammonium phosphate- (10-15%), uric aid (5%) & cystine (1-2%)
silent in renal pelvis, symptomatic in ureter
Prevention; high fluid intake, low sodium & alkaliniaztion of urine
Comp: renal failure \< 5mm stones pass though
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RCC
Etiology: proximal tubule cells arising from cortex (VHL tumor suppresor gene -ch3p)
* sporadic (60 yrs): unilateral, unifocal
* hereditary (5%)- younger adults-Bilateral and multifocal
* associated w/ pheochromocytoma, cerebllar & retinal hemangioblastomas
* 3 types
* clear cells (most common)=glycogen & lipids
* Papillary-psammoma bodies
* chromophobe
* Triad: Painless hematuria, flank oain & flank mass
* comp:
* subtotal nephrectomy leads to FSGS
* sticks under endothelial cells--\> right heart via IVC (invades vessels)
* can cause renal vein thrombiosis--\> left testicular vein--\>varicocele
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WIlms Tumor
Et: WT1 & WT2 on short arm of ch 11
histology; Triphasic all are malgnt
Blastemal
stromal/mesenchymal
Epithelial
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HORSE SHOE KIDNEY
ass: edwards (ch18) & turners disease and wilms tumor
asymptomatic
complications are rare:
* d/t kinking of urterter--\> hydronephorsis--\>recurrent kindne stones/infection
* RCC
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Bladder cancer
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Testicular tumors: epidemiology
1% of all cancer death.
* more common in white americans as compared to asians & africans
* ETIOLOGY;
* Isochrome i(12p)
* Cryptorchidism (10%)
* Testicular dysgenesis (Klinefelter's syndrome)
* Others: radiation
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Testicular Tumor
* Trimodal age distribution:
* Infant & children: teratomas & yolk sac
* 15-30 years; mixed germ cell tumor
* 30-50 years: seminoma
* \>60 years: Lymphomas
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Type 1 diabetes
**Etiology:**
* Coxsackie B4, Rubella Mumps
* HLa DR3 & DR4/DQA1 & DQB1
**Complication:**
**silent MI due to peripheral neuropathy**
* Diabetic Ketoacidosis triggered by infections (pneumonia, UTI)--\> increased cortisol--\> anatagonizes insulin, favoring gluconeogenesis--\>worsens hyperglycemia
* Severe hyperglycemia--\>osmotic diuresis & gross dehydratoin
* Ketone bodies=acetoacteic acid, B-hydroxybutyrate
* Treat with insulin, fluids & K+
* Hypoglycemia d/t insulin overdose
* symptoms: confusion(brain deprived of glucose), sweating, seizures, coma
* txt: dextrose infusion, IM glucagon--\> down regulates insulin
* Lactic acidosis-d/t anaerobic glycolysis
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Type 2 Diabetes
Etiology:
* obese (d/t insulin anatgonists-FAs & TNF) & \>40 years old
* associated with PCOS
* Morre genetic predispostion than Type 1
* Primarily B-cell defect [genetic] + peripheral insulin resistance [obesity]
* hence, no DKA intially but can get it when there is pancreatic burn-out (becomes simila to Type 1)
* Histology
* Localized amyloidosis (also seen in medullary carcinoma of the thyorid)
Complications:
Silent MI due to peripheral neuropathy
* Hyperosmolar, non-ketotic coma d/t dehydration + hyperglycemia
* Lactic acidosis- d/t anaerobuc glycolyisis
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Diagnosis of both Type 1 & Type 2 Diabetes
* 2 samples of fasting blood glucose \> 126mg/dl [hyperglycemia]
* Random blood glucose \>200mg/dl with symptoms of Polyphagia, polydipsia and polyuria.
* HbAc1 \> 6.5% is diagnostic but more useful for evaluation of lonterm glycemic control1
* 2 hr plasma glucose \> 200mg/dl during OGTT (overnight + 75mg glucose)
* Tests residual capacity of pancreas- challenges the pancreas to make insulin
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Acromegally
Et:
* Execessve GH after fusion of the epiphysis (part of MeN-1 syndrome due to MEN 1 gene mutation)
* **MEN1 (PPP):**
* Parathyroid adenoma/hyperplasi (primary hyperparathyroidism. Stones (kidney stones), Bones (osteoporosis), groans (GI symptoms)
* **Anterior Pituitary Adenoma**
* GH adenoma--\>GH--\>IGF1-somatomedin- (liver)
* GH--\>anatgonizes insulin--\>type 2 diabetes & simultaneous reease of prolactin 9inhibits GnRH)--\>decreased LH, FSH
* **Can lead to Pan-hypopituitarism**:
* Pancreatic Tumor (VIPoma, Zollinger Ellison gastrinoma, Insulinoma)
Comp:
* Diabetes, obstructive sleep apnea, osteoarthritis, carpal tunnel, bitemporal hemianopsia, neolastic polyps & **heart failure (most common CoD d/t cardiomegaly + concentric hypertrphpy from HTN)**
* **TXT: transphenoidal surgery**
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Diabetes insipidus
Etiology;
* Central DI: absolute def. of ADH
* Hypothalamic/pituitary
* Nephogenic DI: resistance to ADH action
* Genetic,, metabolic (hypokalemia, hypercalcemia) or lithium
* Hypercalcemia causes aquaporin in CD to be insenstive to ADH--\> decreases urin osmolality--\> polydipsia & polyuria
* INvestigation: water deprivation test
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Grave's Disease
Et: females 20-40 yrs old
* Triad:
* **most common cause in US -Type II HSN (TSIg mimis T3/T4)--\> T cells induce B cells to mak IgG antibodies agains TSH receptors (stimulating Abs)**
1. Thyrotoxicosis (hyperparthyroidim --\> difuuse goiter--\>hear bruit)
2. Ophthalmopathy (exopthalamos b/c fibroblasts have TSH receptors)
3. Pretibial myxedema (non-pitting edema b/c fibroblasts have TSH receptors--\> GAGs)
Complications:
Atrial fibrillation--\> arrythmias (most common COD)
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Hashimoto's Disease
Et: Most common cause of hypothryoidism in the US, world wide=iodine def.
* autoimmune destruction of thyroid glands (HLA DR5, DR3)
Invest:
* Radioactive iodine uptake = cold nodule
* benign nodules= hot or cold
* Malignant nodules= ALWAYS cold!
* decreased T3 & T4, increased TRH & TSH
* Increased TRH--\> increased prolactin--\>blocks GnRH--\>no fsh or LH
* Antibodies: Anti-thyroglobulin, anti-thyroid peroxidase & anti-microsomal (anti-thyroxidase)
Complications:
* Monoclonality of germinal center--\> Non-Hodgkin's B Cell lymphoma!!!
* atherosclerotic plaques--\> MI, stroke, peripheral vascular disease
* Cretinism in children--\> (6P's) Pot belly, protruding tongue, pale, puffy faced, poor brain, protuding umbilicus
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