Quiz 2 Flashcards
1
Q
What is the Henderson hasslebach equation
A
PH= 6.1 + log ([HCO3]/[pCO x 0.3])
2
Q
What are the ranges for academia and alkalemia
A
<7.35 - acidemia
> 7.45 - alkalemia
3
Q
What indicates a respiratory vs metabolic acidosis
A
Metabolic: HCO3 <20
Respiratory: pCO2 > 45
4
Q
What differentiates a metabolic vs respiratory alkalosis
A
Metabolic: HCO3 > 30
Respiratory: pCO2 <35
5
Q
What are some causes of acidosis
A
DKA, lactic acidosis, ingestion of ethylene glycol, methanol, propylene glycol, salicylates; loss of bicarbonate (diarrhea), AKI or chronic kidney dz
6
Q
What conditions cause a normal anion gap metabolic acidosis
A
Diarrhea, ileal loop, renal tubular acidosis, carbonic anhydrase inhibitor, post hypocapnia
7
Q
What causes a high anion gap metabolic acidosis
A
-salicylates, methanol, paraldehye, ethylene glycol, ketoacidosis, EtOH, lactic acidosis uremia
8
Q
What are sx of acidosis
A
Flu - like; tachypnea and tachycardia (catecholamine release), pulm edema, increased serum glucose
9
Q
What is a normal anion gap
A
8-12; its positive because you dont measure albumin
10
Q
What is the compensation formula for metabolic acidosis
A
PCO2 = (1.5 x [HCO3]) + 8 (+/- 2) : if PCO2 doesn’t match then likely mixed
11
Q
What does MUD PILES stand for
A
- Methanol/metformin
- Uremia
- DKA
- Paraldehyde/propylene glycol, phenformin
- Isoniazid/iron toxicity
- lactic acidosis *includes cyanide and CO poisoning, seizures, sepsis an ischemia
- ethanol/ethylene glycol
- salicylates
12
Q
What are some causes of rhabdomyolysis
A
Seizure, extreme exercise, heat stroke, malignant hyperthermia, trauma, crush injury, immobilization, compartment syndrome; statins, SSRI, Cocaine, creatine, alcohol, toluene, CO, quail poisoning, mushroom poisoning; hypokalemia, hypophasphtema, influenza
13
Q
What are the signs and sx of rhabdomyolysis
A
Decreased urine output, reddish brown color (myoglobin), heme + but no RBCs, positive protein, granular casts on micro; elevated CK, hyperkalemia, hypocalcemia, hyperphosphatemia
14
Q
How does DKA occur
A
Intracellular hypoglycemia activates fatty acid degredation which lead to a large amount of ketones
15
Q
Why do people with DKA start vomiting
A
Compensatory mechanism (drives towards alkalosis)
16
Q
What does binge drinking do to insulin levels
A
Decreases them
17
Q
What is ethylene glycol
A
Found in anti-freeze ; metabolized by alcohol DH to glycolic aid an then to oxalic acid; increased NADH levels encourage formation of lactic acid; *presents with intoxication, low BAC level, and HAGMA without ketones, calcium oxalate crystals in urine that fluoresce under wood lamps
18
Q
What is characteristic of methanol poisoning
A
Blurry vision
19
Q
How does salicylate toxicity present
A
Tachypnea (induces a respiratory alkalosis), tinnitus, agitation, seizures, coma, *salicylic acid contributes very little to acid load
20
Q
How does renal failure lead to a high anion gap
A
Accumulation of sulfate, phosphate and other anions
21
Q
Is acidosis common in chronic kidney dz
A
No* buffered by other organs as well as dietary changes and dialysis help prevent this
22
Q
What are the alpha 1 receptor antagonists use to treat BPH
A
Terazosin, doxazosin, tamsulosin, silodosin, alfuzosin
23
Q
What do the alpha 1 antagonists do to treat BPH
A
Relax m tone; *rapid relief of sx (days)
24
Q
What does activation of each of the subsets of the alpha 1 receptors do
A
Alpha 1A: m contraction -> bladder outlet obstruction
Alpha 1D: detrusor instability
25
What do alpha 1 antagonists compete with
NE
26
Which alpha antagonists are not uroselective
Terazosin and doxazosin
27
What are the side effects of terazosin and doxazosin
Postural hypotension, dizziness, fatigue
28
What receptors are tamsulosin and silodosin specific or
Alpha 1A and alpha 1D
29
What are the side effects of tamsulosin an silodosin
Reduced ejaculation; IFIS (floppy iris syndrome)
30
Is alfuzosin specific for certain alpha 1 Receptors
No; but it is uroselective
31
What are the side effects of alfuzosin
QT prolongation
32
What drug interactions do all alpha 1 antagonists have
interact with PDE-5 inhibitors (sildenafil and vardenafil)
33
Which alpha 1 antagonists are metabolized by CYP 3A4
Tamsulosin, silodosin, alfuzosin
34
When should you avoid administration of alfuzosin
Hepatic impairment
35
When should you take alfuzosin
Immediately after same meal every day
36
What are the steroid 5alpha reductase inhibitors
Finasteride and dutasteride
37
What do the steroid 5alpha reductase inhibitors do
Prevent enlargement of and shrinks prostate; *delayed action - 3-6 months
38
What does a hyperplastic prostate have elevated levels of
SAR 2
39
Which steroid 5 alpha reductase inhibitor is specific
Finasteride (SAR-2); dunastride is a DUal inhibitor SAR 1 and 2
40
What is the effect of 5alpha reductase inhibitors on PSA
Decreases it
41
Which 5 alpha reductase inhibitor is more efficient at decreasing SERUM DHT
Dutasteride
42
What are the side effects of finasteride and dutasteride
ED, gynecomastia, depressed libido, ejatulation disturbances
43
Do the 5 alpha reductase inhibitors have drug interactions
No; but use caution with liver abnormalities by hepatic CYP3A
44
When do you use combination therapy for BPH
Severe sx of BPH, known to have large prostate, no response from monotherapy
45
What is tadalafil
PDE-5 inhibitor used to treat BPH an ED
46
What are the risk factors for ED
Obesity, smoking, stress, CV dz, adverse drug effect (diuretics, SSRI)
47
What are people with extrosphy of the bladder at risk for
Colonic glandular metaplasia and infections; adenocarcinoma
48
What are urachal cysts lined by
Either urothelium or metaplastic glandular epithelium
49
What kind of cancer can arise from urachal cysts
Carcinomas
50
What is the morphology of cystitis
Acute: hyperemia and neutrophil infiltrate *patients receiving cytotoxic antitumor drugs my developer hemorrhagic cystitis (adenovirus also causes this)
51
What is follicular cystitis
Presence of lymphoid follicle within the bladder mucosa
52
What is interstitial cystitis
Aka chronic pelvic pain syndrome; women; intermittent Supra public pain, urinary frequency, urgency, hematuria and dysuria, and cystoscope findings of fissures nd punctuate hemorrhages in the bladder mucosa; some are assoc with chronic mucosal ulcers (hunger ulcers) *increase mast cells is characteristic; r/o CIS
53
What is malakoplakia
Chronic inflammatory reaction that stems from acquired defects in phagocyte function; arises in setting of chronic bacterial infection occurs more in immunosuppressed transplant recipients
54
What is the morphology of malakoplakia
Soft yellow raised mucosal plaques filled with foamy macrophages that have abundant granular cytoplasm; *michaelis-Gutmann bodies present within macrophages (mineralized oncrtions from calcium in lysosomes)
55
What is polyploid cystitis
Inflammatory lesion resulting from irritation of the bladder urotheliumis thrown into broad bulbous polyploid projections
56
What is cystitis glandularis/cystica
Nests of urothelium (brunn nests) grown downward into lamina propria; epithelial cells in the center undergo metaplasia to cuboidal or columnar (glandularis) or retract to produce cystic spaces lined by flattened urothelium (cystica)
57
What is a nephrogenic adenoma
Unusual lesion that results from implantation of shed renal tubular cells at sits of injured urothelium; this tissue can be replaced by cuboidal epithelium whih can assume a papillary growth pattern
58
What are the precursor lesions to urothelial carcinoma
Noninvasive papillary tumors (most common) and flat noninvasive urothelial carcinoma
59
Invasion of what worsens the prognosis of bladder cancer
Muscularis propria
60
Is carcinoma of the bladder more common in men or women
Men
61
What are risk factors for bladder carcinoma
- smoking
- exposure to Aryl amines
- schisto haematobium (but mostly squamous)
- long term use of analgesics
- heavy long term exposure to cyclophosphamide (immunosuppressant) induces hemorrhagic cystitis
- irradiation
62
What mutations are seen in bladder cancer
- GOF of *FGFR3 (found in noninvasive low-grade papillary carcinomas)
- LOF in TP53 and RB (high grade and muscle invasive tumors)
- *HRAS activation (low grade noninvasive)
* =exclusive in bladder cancer
63
Losses of what chrom are common in bladder tumors
9; early events - first lose FGFR3, RAS and chrom 9 then lose TP53 and or RB
64
What is the morphology of papillary lesions of the bladder
Red, elevated; multiple tumors often present
65
What is the morphology of bladder papillomas
Often present in younger patients; single; attached by a stalk - exophytic; histo identical to urothelium; recurrences and progression rare; inverted papillomas are benign insisting o rods of urothelium that extend into the lamina propria
66
What are phosphodisterase inhibitors (PDE-5 inhibitors)
Sildenafil; competitive inhibitors
67
Which PDE-5 inhibitor has the fastest onset of action
Avanafil
68
Which PDE-5 inhibitors has the longest duration of action
Tadalafil (36 hrs)
69
Which PDE-5 inhibitors have to be taken on an empty stomach
Sildenafil an vardenafil
70
Which PDE-5 inhibitor has the longest half life
Tadalafil
71
What are the side effects of sildenafil, vardenafil, avanafil
Blue vision and blurred vision
72
What are the side effects of tadalafil
Back pain, myalgia, limb pain
73
What are the contraindications for PDE-5 inhibitors
Organic nitrates (extreme hypotension);
- specific to vardenafil: patient needs to be hemodynamically stable
- specific to tadalafil: when used or BPH, concurrent alpha 1 blockers not recommended
- specific to sildenafil: concurrent alpha blockers initiated at lowest dose
74
What are the second line ED therapies
Vacuum erection devices and penile injections with alprostadil (prostaglandin E1)
75
How does alprostadil work
Increased cAMP, decreased iCa2+, smooth m relaxation and eretion
76
What are the side effects of alprostadil
Prolonged erection (priapism) *medial emergency -> can result in permanent corporal fibrosis and ED; tx with sympathomimetic (phenlephrine) and aspiration
77
What is pagetoid spread
Scattered malignant cells in otherwise normal epithelium
78
What are mixed urothelial carcinomas with areas of SCC
More frequent than pure SCC of the bladder; typically invasive, fungating tumors or are ulcerative and infiltraive
79
What is a good screening method for CIS
FISH of urine samples for aneuploidy of chrom 3,7,17, and 9p
80
What do patients at high risk of recurrence or progression (CIS, papillary high grade tumors, Multifocal or LP invasion) get for treatment
Intravesical instillation of attenuated Mycobacterium Boris called bacillus calmette-guerin-> elicits inflammatory response that kills tumor
81
What is radical cystectomy reserved for
Tumors invading muscularis propria, CIS or high grade papillary cancer refractory to BCG, CIS extending into prostatic urethra and prostatic ducts (BCG cant reach)
82
What is the most common benign mesenchymal tumor of the bladder
Leiomyoma
83
What is the most common sarcoma in infancy or childhood
Embryonal rhabdomyosarcoma can manifest as polyploid grape like mass called a sarcoma botryoides
84
What is the most common sarcoma in the bladder in adults
Leiomyosarcoma
85
What are the most common causes of obstruction of the bladder outlet
Males: prostate enlargement
Females: cystocele
86
What an happen secondary to BPH
Hypertrophy and trabeculation of bladder wall
87
What is an example of non infectious urethritis
Reactive arthritis
88
What is a urethral caruncle
Inflammatory lesion that presents as a small red painful mass at the external urethral meatus usually in older females; consists of inflamed granulation tissue covered by intact but extremely friable mucosa which can ulcerate and bleed *surgical excision
89
What are the benign tumors of the urethra
squamous and urothelial papillomas, inverted urothelial papillomas, condylomas
90
What is primary carcinoma of the urethra
- proximal urethra: analogous to those occurring within later
- distal: SCC
- adenocarcinomas are rare but when they do occur, occur more often in women
91
What is the difference between epi and hypospadias
Epi is on dorsal side; hypo is on ventral
92
What are complications of hypospadias/epispadias
UTI, infertility
93
What is phimosis
When orifice of prepuce is too small to permit its normal retraction; frequently the result of repeated infection; favors development of secondary infections and possibly carcinoma
94
What is balanoposhitis
Infection of glans and prepuce; caused by candida, aerobic bacteria, gardnerella, and pyogenic bacteria; most cases occur cause of poor local hygiene in uncircumcised males -> accumulate smegma
95
What is the morphology of condylomata acuminata
Single or multiple sessile or pedunculated red papillary excrescences; superficial hyperkeratosis and thickening of underlying epidermis (acanthosis); no dysplasia; koilocytosis (vacuolization of squamous cells)
96
What is peyronie dz
Results in fibrous bands involving corpus cavernousum; lesions result in penile curvature and pain during intercourse
97
Which lesions of the male external genitalia display CIS
Bowen dz and bowenoid papulosis; strong association with infection by HPV type 16
98
What is Bowen dz
Occurs in men and women, usually > 35; in me: involves skin of shaft and scrotum; appears as solitary thickened gray-white opaque plaque; can manifest on the glans and prepuce s single or multiple shiny red velvety plaques histo: epidermis is hyperproliferative, dysplastic can transform to SCC
99
What is bowenoid papulosis
Occurs in sexually active adults; distinguished from Bowen dz by younger age of affected patients and presentation as multiple reddish brown papular lesions; never develops into invasive carcinoma
100
What confers protection against SCC of penis
Circumcision (rare in Jews and Muslim)
101
What increases risk of SCC of penis
HPV and smoking
102
What is an uncomplicated UTI
Nonpregnant outpatient women without an atomic abnormalities or instrumentation of urinary tract
103
What is a complicated UTI
Urinary obstruction, urinary retention cause by neuro dz, immunosuppression, renal failure, renal transplantation, pregnancy, foreign bodies (calculus, indwelling catheters)
104
What makes up the biofilm or UPEC
*type I pile, antigen 43, curli
105
What makes up the biofilm for proteus
Produces urease; calcium crystals an magnesium ammonium phosphate precipitates; crystalline biofilm
106
What makes up the pseudomonas biofilm
Micro colony formation by changing hyrophobicity of bacteria surface; lectins and rhamnolipids
107
What makes up the biofilm of e.fecalis
Fibrinogen
108
What are the first line treatments for uncomplicated cystitis
Nitrofurnantoin and fosfomycin; also TMP-SMX (trimethoprim-sulfamethoxazole)
109
What bacteria are resistant too nitrofurantoin
Pseudomonas and proteus
110
What is the pharmokinetics of nitrofurantoin
Metabolized and excreted so quickly that dont have systemic abx actions
111
What are the adverse effects of nitrofurantoin
Antagonizes nlidixic acid (quinolone abx)
112
What are the contraindications for nitrofurantoin
G6PDH deficiency
113
What is the MOA of fosfomycin
Cell wall synthesis inhibitor; inhibits enolpyruvate transferase by binding to cysteine residue of active site and blocking addition of phosphoenolpyruvate to UDP-N-acetyleglucosamine
114
How is resistance to fosfomycin developed
Inadequate transport of drug into cell
115
What form is fosfomycin given in
Only oral; poor bioavailability
116
When should nitrofurantoin and fosfomycin not be taken
If suspicion of early Pyelonephritis (does not achieve adequate levels in kidneys)
117
What are the second line abx for cystitis
Oral beta lactams:
- amoxicillin: aminopenicillin
- cefpodoxime: 3rdd gen cephalosporin
- cefdinir: 3rd gen cephalosporin
- cefadroxil: 1st gen cephalosporin
* less effective than fluoroquinolones but have less side effects so are second line
118
What are the third line agents for cystitis
Fluoroquinolones: ciprofloxacin, levofloxacin, ofloxacin
119
What are the adverse effects of fluoroquinolones
Tendinitis and tendon rupture, peripheral neuropathy, CNS effects
*effects outweigh benefits in treating uncomplicated cystitis
120
What should you give if there is resistance to cystitis treatment
Ertapenem: good activity against gram neg, pos, and anaerobes but is inactive against pseudomonas
121
According to Dr. Sheehy does cystitis present with a fever
No
122
What are the first line agents for pyelonephritis
Fluoroquinolones: ciprofloxacin or levofloxacin
* if severe pyelonephritis or risk factors for resistance -> administer with parenteral broad spectrum abx until susceptibility data is available (ceftriaxone or aminoglycosides - gentamicin and tobramycin)
123
What are the aminoglycosides active against
Aerobic gram - and pseudomonas
124
What is the MOA of aminoglycosides
Irreversible protein synthesis inhibitor - binds to 30S ribosome SU -> production of nonfunctional proteins
125
What are the adverse effects of aminoglycosides
Eighth CN toxicity, renal toxicity, NMJ blockade
126
What are the second line agents for pyelonephritis
TMP-SMX, oral beta lactams (amoxicillin, cefpodoxime, cefdinir, cefadroxil), if patient cant tolerate these agents -> aztreonam
*used in cases of fluoroquinolone hypersensitivity or resistance
127
How is aztreonam administered
IV
128
What are the adverse affects of aztreonam
Neutropenia, pain at injection site
129
What do you us for complicated cystitis
Ciprofloxacin or levofloxacin
130
What do you use for complicated pyelonephritis
- mild: ceftriaxone, ciprofloxacin, levofloxacin or aztreonam
- severe: beta lactam + beta lactamase inhibitor or a carbapenem
131
What does the presence of a gram postiive cocci on gram stain suggest for a case of cystitis
E faecalis or E faecium; to with ampicillin or amoxicillin
132
What is phenazopyridine
Urinary analgesia; can cause significant nausea an colors the urine orange/red
133
Which first line agents for complicated pyelonephritis cover pseudomonas
Ciprofloxacin and levofloxacin
134
What are the agents used for severe complicated pyelonephritis
- cefepime
- piperacillin + tazobactam
- ceftolozane + tazobactam
- ceftazidime + avibactam
- meropenem
- imipenem
- doripenem
135
What organisms do tazobactam and avibactam work well against
Good inhibitors of ambler class A beta lactamase: produced by staph, H. Influenzas, gonorrhea, salmonella, shigella, coli, klebsiella
*poor against class C: enterobacter, pseudomonas
136
Are carbapenems resistant to beta lactamase
Yes
137
What is the MOA of carbapenems
Inhibits transpeptidase
138
Which carbapenem has the longes half life
Ertapenem
139
What is the adverse effect of imipenem
Seizures
140
What pathogen causes prostatitis most commonly
E coli
141
What is the clinical presentation of prostatitis
Dysuria, urgency, Fever, pain; prostate is warm, firm, edematous
142
What is the treatment for prostatitis
TMP-SMX, ciprofloxacin, levofloxacin
143
How do you treat a recurrrent group A beta hemolytic strep infection
Repeat treatment should be with greater beta lactamase stability
- penicillin G
- cephalexin or cefadroxil (1st gen)
- cefpodoxime or cefdinir (3rd gen)
- amoxicillin or clindamycin
144
What is the MOA of clindamycin
Binds 50s SU and inhibitors protein synthesis
145
What is the morphology of SCC of the penis
Two types: papillary and flat
- papillary forms cauliflower mass that fungates
- flat: epithelial thickening accompanied by graying and fissuring
146
What is verrucous carcinoma
Exophytic well differentiated variant of SCC that is locally invasive but rarely metastasizes
147
What are the major lesions of the testis vs epididymis
Testis: tumor
Epididymis: inflammatory diseases
148
What is synorchism
Fusion of testes
149
What are the phase of descent of the testis
- transbdominal: testis lie within lower abdomen; controlled by mulllerian inhibiting substance
- inguinoscrotal phase: descend through inguinal canal to scrotal sac androgen dependent
150
What is the most common site of undescended testis
Inguinal canal usually unilateral
151
What is the morphology of cryptorchidism
- arrested germ cell development associated with marked hyalinization and thickening of the BM of the spermatic tubules
- leydig cells spared
- small and firm
152
What is orchiopexy
Placement of undescended testicle in the sac
153
What is thought to cause cryptorchidism
Defect in testicular development and differentiation; not anatomy
-cancer can occur in contralateral testicle as swell
154
What can cause testicular atrophy
- progressive atherosclerotic narrowing of the blood supply in old age
- end stage of inflammatory or orchitis
- cryptorchidism
- hypopituitarism
- generalized malnutrition or cachexia
- irradiation
- prolonged administration of antiandrogens
- exhaustion atrophy (following persistent stimulation by FSH)
155
What infections affect the testis vs epididymis
Testis: syphilis
Epididymis: gonorrhea and tuberculosis
156
What are the most common causes of epididymitis in diff age groups
- childhood: gram - rods
- younger than 35: chlamydia and gonorrhea
- older than 35: E. coli and pseudomonas
157
What is idiopathic granulomatous orchitis
Granuloma restricted to spermatic tubules; autoimmune cause suspected
158
How does gonorrhea progress in males
Urethra -> prostate -> seminal vesicles -> epididymis (abscesses)
159
When does mumps more commonly produce orchitis
Postpubertal
160
How does syphilis affect the male GU tract
Gumma formation and diffuse interstitial inflammation that produces obliterative endarteritis associated its perivascular cuffs of lymphocytes and plasma cells
161
What is the difference between neonatal and adult torsion
Adult: results from bilateral an atomic feet that leads to increased mobility of the testes (bell clapper abnormality) - fix this by orchiopexy
162
What are the spermatic cord tumors
- lipomas: common - involve proximal spermatic cord; usually just pulled fat from retroperitoneum by a hernia (not true neoplasm)
- most common* - adenomatoid tumor; mesothelioma but NOT referred to as mesotheliomas; typically near upper pole of epididymis; benign; can be minimally invasive
- most common paratesticular tumors are rhabdomyosaromas in children and liposarcomas in adults
163
What is the difference between germ cell and sex cord tumors
Germ cell - malignant
| Sex cord - tend to be benign
164
What are the germ cell tumors divided into
- seminomatous: seminoma and spermatocyticc seminoma
| - nonseminomatous: embryonal carcinoma, yolk sac, choriocarcinoma
165
What are the sex cord stromal tumors
Leydig cell or Sertoli cell tumor
166
What population are germ cell tumors more common in
Whites
167
What are testicular germ cell tumors associated with
Testicular dysgenesis syndrome (TDS): cryptorchidism, hypospadias, and poor sperm quality *increased by in utero exposure to pesticides and nonsteroidal estrogens
168
What is klinefelter associated with an increase risk of
Mediastinal germ cell tumors but not testicular tumors
169
What genetic factors have been linked to germ cell tumors
-KIT and BAK
170
What is the precursor lesion for testicular germ cell tumors
Intratubular germ cell neoplasia (ITGCN)
171
Which germ cell tumors do not typically arise from a precursor lesion
- pediatric yolk sac tumors and tertomas
| - adult spermatocytic seminomas
172
What is the pathogenesis of germ cell tumors
Precursor lesion believed to occur in utero and stay dormant until puberty when it progresses; the precursor lesion cells retain xpresion of OCT3/4 and NANOG which are impt in maintenance of pluripotent stem cells; have reduplication of short arm of chrom 12 in the form of an isochrom (*always found in germ cell tumors)
173
What is the equivalent tumor of a seminoma in the female
Dysgerminoma
174
What do seminomas express.
Contain isochrome 12p and express OCT3/4 and NANOG
175
What is the morphology of a seminoma
Sheets of uniform cells divided into poorly demarcated lobules by delicate fibrous septa containing lymphocytic infiltrate; large and round to polyhedral and has distinct cell membrane, clear o watery-appearing cytoplasm; large central nucleus with one or two prominent nuclei; stain positively for KIT, OCT4 and placental alkaline phosphatase (PLAP) 15% contain syncytiotrophoblasts (HCG elevated)
176
What is spermatocytic seminoma
Typically affects older men; excellent prognosis; contain 3 cell populations: medium sized cells, smaller cells with a narrow rim of eosinophilic cytoplasm, and scattered. Giant cells; *lack lymphocytes, granulomas, syncytiotrophoblasta, extra-testicular sites of origin, admixture with other germ cell tumors and association with ITGCN
177
What are the features of embryonal carcinoma
- occur in 20-30 y/o age group
- more aggressive than seminomas
- smaller than seminomas
- extension through tunica albuginea typically occurs
- foci of hemorrhage or necrosis sen; histo: cells grow in alveolar or tubular pattens sometimes with papillary convolutions
- markers: OCT3/4, PLAP, ***cyotokeratin and CD30 and negative for KIT (characteristic)
178
What is a yolk sac tumor aka endodermal sinus tumor
Most common testicular tumor in infants and children up to 3 years; very good prognosis at this age; compose of lace-like (reticular) network of cuboidal or flattened cells; Schiller-Duvall bodies (consist of mesodermal core with central capillary and visceral and parietal layer of cells resembling primitive glomeruli) hyalin like globules in which alpha fetoprotein and alpha antitrypsin can be seen*
179
What is fanconi syndrome
Dz of proximal renal tubular; filtered glucose, aa, Uric acid, phosphate, bicarbonate are not reabsorbed
180
What are the clinical features of fanconi
Polyuria, polydipsia, hypovolemia, hypophosphatemic Ricketts (kids), osteomalacia (adults), growth failure, type 2 RTA, hypokalemia, hyperchloremia, hypophosphatemia, glycosuria (can also be caused by SGLT2 inhibitors)
181
What are the causes of fanconi
Cystinosis, galactosemia, glycogen storage, tyrosinemia, Wilson’s, malignancy, multiple myeloma, nephrotic syndrome, renal transplant, heavy metals, meds (tenofovir, valproate, gentamicin)
182
How do you tx fanconi
Replace substances wasted; use citrate to replace HCO3, phosphate, vit D, if genetic -> minimize intake of substance not handled properly
183
What is the main difference between barter syndrome and gitelmann syndrome
Barttman: concentrating capacity and diluting capacity are reduced
Gitelmann: concentrating capacity is normal but diluting capacity is reduced
184
What is classic barrters syndrome
Type 3 -> mutation in Cl channel in loop of henle
185
What is the inheritance pattern of bartter
AR
186
What is the presentation of barter syndrome
-neonatal form: polyhydramnios, polyuria/dipsia with hypercalcuria after birth
-classic form: no noticeable symptoms until school age; polyuria/dipsia, vomiting and growth retardation
Sx identical to those taking loop diuretics
187
How do you tx barter syndrome
Increases in dietary sodium and potassium; potassium sparing diuretics to limit K loss; NSAIDs -> decreases production of PGE2 which helps the abnormalities seen in barter
188
What are PE findings of barter
Normal to low BP, polyuria/dipsia, elevated plasma renin and aldosterone, hypokalemia, hyponatremia, hypocalcemia, hypomagnesmia, hypochloremic metabolic alkalosis, hyperglycemia, hyperuricemia, increased cholesterol *isotonic urine
189
What is gitelmann syndrome
AR that affects the distal tubule; usually presents in late childhood more severe in females; patients usually have mutations in gene coding for thiazide sensitive Na-Cl cotransporter (NCCT); mimics chronic use of thiazide diuretics; may develop HTN at later age
190
What is the presentation of gitelmann syndrome
Polyuria/dipsia, hypokalemia, hypercalcemia, hyponatremia, hypomgnesemia, hypochloremic metabolic alkalosis, hyperglycemia, hyperuricemia, incrased cholesterol; can dilute or concentration urine
191
What is the tx for gitelmann syndrome
Taking in enough NaCl and providing supplementation of potassium and magnesium (will increase GI side effects so aim for stable hypokalemia and borderline hypomagnesemia) aldosterone antagonist can stabilize hypokalemia
192
Is barter or gitelman more benign
Gitelman
193
What is the defect in Liddle syndrome
ENaC channels dont degrade in principle cells; increased sodium reabsorption with potassium loss; AD
194
What are the sx of liddle syndrome
(Pseudoldosteronism); severe HTN, low plasma renin activity, low aldosterone, metabolic alkalosis, hypokalemia
195
What is pseudohypoaldosteronism
Caused by a failure of response to aldosterone leading to renal tubular acidosis and hyperkalemia; levels of aldosterone are actually elevated; therapy requires large amount of sodium
196
What are the features of types I, II, and IV of RTA
Type I: decreased excretion of H+ and NH4; normal anion gap
Type II: loss of HCO3 b/c cant reabsorb it; normal anion gap hyperchloremia
Type IV: hypoaldosteronism; decreased excretion of NH4; hyperkalemia inhibits NH3 synthesis; normal anion gap
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What are the features of all RTAs
Acidemia, normal anion gap, normal serum creatinine, and NO diarrhea
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What is the most common RTA
Type IV; hyperkalemic*; plasma HCO3 is >17; urine pH is typically <5.5; common causes: diabetic neuropathy, harmonic interstitial nephritis, drugs: ACEI, ARB, heparin, NSAIDs, spironolactone
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What is the plasma K+ in RTA type I vs type I
Type I: low, but fixed with alkali therapy
| type II: low, but worsened by alkali therapy
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What are some common causes of RTA type I
Autoimmune disorders, kidney transplant, hypercalcuria, sickle cell, cirrhosis, analgesic nephropathy
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What are the common causes of RTA type 2
Fanconi, in adults: multiple myeloma, drugs
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Where is the location of the deficit in each of the RTAs
Type I: distal
Type II: proximal
Type IV: adrenal
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Which RTA causes the most severe acidosis
Type I
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What are other presenting features of RTA I
Urinary stone formation b/c hypercalcuria with low urinary citrate and alkaline urine; bone demineralization
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How do you tx RTA I
Restoring normal growth and preventing kidney stones is goal; sodium bicarbonate or sodium citrate to treat acidosis; correction of low K, Ca and salt
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How do you tx RTA 2
Treat underlying cause; children with this disorder: give large doses of potassium citrate (oral alkali)
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How do you tx RTA 4
Therapy aimed at reducing potassium; low potassium diet and loop diuretic; alter drug doses
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What is the morphology of choriocarcinoma
Do not cause testicular enlargement; small palpable nodul; hemorrhage and necrosis extremely common; histo 2 cell types - syncytiotrophoblast(large multinucleated contain HCG) and cytotrophoblast (polygonal with clear cytoplasm row in cords or masses and have single nucleus)
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What does hemorrhage and necrosis with a teratoma usually indicate
Admixture with embryonal carcinoma and/or choriocarcinoma
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What is the importance of recognizing a non-germ cell malignancy arising in a teratoma
These secondary tumors are chemo resistant
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When are teratomas considered malignant
In postpubertal male
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Do you usually bx testicular masses
No because there is a risk of tumor spillage; the standard management of solid testicular mass is radical orchiectomy based on presumption of malignancy
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How do testicular tumors spread
Lymphatic - retroperitoneal para aortic nodes are first to be involved; hematogenous to lungs primarily
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What are the differences between seminomas and nonseminomatous germ cell tumors
- seminomas tend to remain localized to the testis; NSGCTS spreads faster
- Mets from seminomas involve LN; NSGCTs use hematagenous route
- NSGCT - poorer prognosis
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What are the stages of testicular tumors
I: confined to testis, epididymis or spermatic cord
II: distant spread confined to retroperitoneal nodes below diaphragm
III: met outside the retroperitoneal nodes or above the diaphragm
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What does the elevation of lactate DH indicate
Mass of tumor cells; assesses tumor burden
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What tumor produces AFP
Yolk sac
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How can serum markers be used in testicular tumors
Elevation of AFP or HCG father orchiectomy indicates stage II dz; monitoring response to therapy
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What are the sx of leydig cell tumors
Testicular swelling, gynecomastia
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What is the morphology of leydig tumors
Large, polygonal, cytoplasm contains lipid droplets, lipofuscin, *crystalloids of reinke
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What are gonadoblastomas
Composed of germ cells and stromal elements
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What is the most common form of testicular neoplasm in men over 60
Non-Hodgkin lymphoma; most common is diffuse B cell lymphoma, Burkitt, and EBV positive extra nodal; * have high propensity for CNS involvement
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What is the tunica vaginalis
Mesothelial lined surface exterior to the testis that can accumulate fluid (hyrocele); rarely can develop mesothelioma; hematocele; chylocle - lymph (elephantiitis)
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Where do most prostatic hyperplasia occur
Transitional zone
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Where do most carcinomas of the prostate occur
Peripheral zone
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What causes acute bacterial prostatitis
Bacteria similar to those that cause UTI E. coli and staph; fever, chills, dysuria; on rectal exam, prostate is tender and boggy; dx via urine culture
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How do you dx chronic bacterial prostatitis
Leukocytosis in the prostatic secretions and positive bacterial cultures
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What is the most common form of prostatitis
Chronic abacterial prostatitis; no hx of UTI*; leukocytes in prostatic secretions but culture is negative
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What causes granulomatous prostatitis
Most common: instillation of BCG within the bladder for treatment of superficial bladder CA; requires no tx; can also be caused by rupture of prostatic ducts
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What are the syndromes that include wilms tumor
- WAGR: wilms, aniridia, genital, retardation
- denys-drags: gonadal and renal tumors
- beckwith-wiedemann: non-WT1; IGF2
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What cells are hyperplastic in BPH
Stromal and epithelial lols
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Is there increased epithelial proliferation in BPH
No; postulated that it forms from lack of cell death
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What is the difference between type 1 and 2 5 alpha reductase
Type I: is in liver and skin
| Type II: in prostate (stromal cells; not epithelial)
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What does DHT bind to
Nuclear androgen receptor in stromal and epithelial prostate cells; has a higher affinity than testosterone -> stimulates formation of FGF and TGF beta; increases proliferation of stromal cells and decreases death of epithelial cells
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What is the morphology of BPH
-early, just stromal cells; late predominantly epithelial; median lobe hypertrophy; nodules that contain mostly glands are yellow-pink an soft and exude milky white prostatic fluid; nodules that are composed of fibromusclar stroma are pale gray and tough and do not excrete fluid
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What can BPH cause downstream
Bladder hypertrophy and distention with urine retention; infection;
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How is BPH treated
Decreased fluid intake, moderating intake of alcohol and effeminate, timed voiding schedules; alpha blockers; 5 alpha reductase inhibitors; severe: transurethral resection of prostate
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What population does prostatic cancer most frequently occur in
Black
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What products prevent prostate cancer
Lyopenes (tomato’s), soy, vitamin D
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What does the X-linked AR gene contain
CAG repeats; AR with shortest CAG repeats have highest sensitivity to androgens - found in AA
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How do tumors evade antiandrogen treatment
Acquiring hypersensitivity to low androgen levels (AR gene amplification), ligand-independent AR activation, mutations in AR that allow it to be activated by non-androgen ligands; increased PI3K/AKT signaling (loss of PTEN)
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What genes are associated with prostate cancer
BRCA2, HOXB13 (familial)
- chromosomal rearrangements that juxtapose the coding sequence for ETS family TF genes (ERG or ETV1) next to anyone regulated TMPRSS2 promoter -> leads to overexpression of ETS which makes normal epithelial cells more invasive
- deletions and amplifications are more common; amplification of 8q24 containing MYC and deletions of PTEN; late stage: loss of TP53 and RB
- hypermethylation of glutathione s transferase (GSTP1) - downregulates GSTP1 expression - prevents damage from carcinogens
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What is the precursor lesion to prostate cancer
Prostatic intraepithelial neoplasia (PIN) but not referred to as CIS
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What is the morphology of prostate cancer
Gritty and firm; local extension involves seminal vesicles and base of urinary bladder; Mets via LN to obturator nodes and para aortic node; hematogenous spread to bones (typically osteoblastic) - most common in lumbar spine, proximal femur, pelvic, thoracic spine and ribs; *outer basal cell layer that lines benign glands is absent (but is found in PIN); *histo features specific for prostate cancer: perineural invasion; use alpha methylacyl coenzyme A racemase (AMACR) as immuno marker
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What are the prognostic predictors for prostate cancer
Grade and stage
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What is the Gleason system
Grade I: most well differentiated tumors - grade 5: no glandular differentiation with tumor cells infiltration the stroma in cords, sheets and nests
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How is Gleason score calculated
Primary stage + secondary stage; if only one pattern, double it; if three pattens most common and highest grade adde
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What does each range of Gleason scores indicate
2-6:excellent prognosis
| 7-10: poor prognosis
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What are the stages of prostate cancer
T1: incidentally found
T2: organ confine
T3a and b: extra prostatic extention with and w/o seminal vesicle invasion, respectively
T4: direct invasion of contiguous organs
N0: no LN met
N1: met in LN
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What is needed to confirm the dx of prostate cancer
Trans rectal needle biopsy
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What form of PSA is more prominent in cancer vs BPH
BPH: free
Cancer: bound to alpha 1 antichymotyrpsin
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Which genes are biomarkers for prostate cancer
PCA3 (urine); combined with urine screening for TMPRSS2-ERG fusion may have increased sensitivity than PSA alone
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What is the most common tx for local prostate cancer
Radical prostatectomy
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How is advanced met carcinoma treated
Androgen deprivation by orchiectomy or administration o analogs of LHRH
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What is the prognosis for ductal adenocarcinoma of the prostate
Poor
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What is colloid carcinoma of the prostate
Carcinoma that reveals abundant mucinous secretions
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What is the most aggressive form of prostate cancer
Small cell (aka neuroendocrine)
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What is the most common cancer that secondarily involves the prostate
Urothelial cancer
