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IPFC 3 Midterm 2 > Men's health Pathophysiology > Flashcards

Men's health Pathophysiology Flashcards

1
Q

Define male hypogonadism

A

Clinical syndrome resulting from failure to produce testosterone OR normal amounts of sperm or BOTH
- needs both

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2
Q

What enzyme used to turn testosterone to dihydrotestosterone DHT? What is DHT responsible for? (2)

A

5a-reductase

Responsible for:
1. External genitalia
- differentiation during gestation
- maturation during puberty
- adult prostatic disease

  1. Hair follicles
    - increased growth during puberty
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3
Q

What enzyme used to turn testosterone to estradiol? What is estradiol responsible for? (2)

A

CYP19 (aromatase)

Responsible for:
1. Bone
- ephiphyseal closure
- increased density

  1. Libido
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4
Q

What is testosterone alone used for without getting converted into anything (4)

A
  1. Internal genitalia
    - wolffian development during gestation
  2. Skeletal muscle
    - increased mass and strength during pubery
  3. Erythropoiesis
  4. bone growth
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5
Q

Differentiate between primary and secondary hypogonadism
Disease type?
low test + LH/FSH levels?
Fertility?

A

Primary
- Disease of testes
- LH/FSH levels high
- Fertility cannot be restored, seminiferous tubules damaged

Secondary
- Disease of hypothalamus or pituitary
- LH/FSH levels low or normal
- Fertility CAN be restored, using GnRH therapy

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6
Q

Define late-onset male hypogonadism

A
  • clinical and biochemical syndrome characterized by an unequivocally and consistent deficiency of testosterone WITH symptoms and signs that can be caused by testicular and/or hypothalamic dysfunction
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7
Q

What age group would you suspect primary hypogonadism? Secondary?

A

From 20-50
- likely primary

50+
- more often secondary but primary still occurs

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8
Q

What is the age-related defects that occur at the hypothalamic-pituitary-testicular axis?
Which is likely the main cause of declining androgen levels?

A
  • Pulsatile GnRH secretion effect reduced
  • LH response to GnRH is reduced
  • Testicular response to LH impaired
    (likely the main cause of declining androgen levels)
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9
Q

What are the MOST specific symptoms of late-onset hypogonadism? (3)

A
  • Decreased libido
  • ED
  • Decreased frequency of morning erections
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10
Q

What are less-specific symptoms of late-onset hypogonadism

A
  • decreased energy
  • decreased motivation
  • changes in mood (depression,anger)
  • Impaired memory
  • inability to concentrate
  • sleep disturbances
  • hot flushes
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11
Q
A
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12
Q

What are signs of late-onset hypogonadism

A
  • decreased body/facial hair
  • central obesity
  • decreased testicular volume
  • decreased muscle mass
  • increased body fat
  • gynecomastia (large breasts)
  • osteoporosis
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13
Q

Is there evidence for testosterone treatment to help with decreased muscle mass, higher visceral fat mass, insulin resistance etc..

A

Low total and Free testosterone levels are weakly associated with multiple adverse outcomes

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14
Q

When should you measure testosterone levels?

A

Measure in morning between 7 - 11
OR
3 hours after you wake up

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15
Q

How much % of testosterone is bound to serum proteins?
Which protein is testosterone bound to that does not make it bioavailable?

A

98% is bound to serum proteins
- 44% is bound so SHBG (not bioavailable)

Sex hormone binding globulin increases with aging

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16
Q

When do we measure free testosterone (3)

A
  1. when SHBG may be decreased
  2. when SHBG may be increased
  3. Total testosterone is borderline/low normal
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17
Q

What conditions and drugs decrease SHBG?

A

Conditions
- obesity
- diabetes
- hypothyroidism
- nephrotic syndrome
- polymorphisms in SHBG gene

Drugs
- glucocorticoids
- progestins
- androgenic steroids

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18
Q

What conditions and drugs increase SHBG?

A

Conditions
- Aging
- HIV
- Cirrhosis and hepatitis
- hyperthyroidism
- polymorphisms in the SHBG gene

Drugs
- anticonvulsants
- estrogens

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19
Q

What is the pathogenesis of androgenetic alopeica? (3)

A

Androgen dependent trait that requires a genetic predisposition.
- Located on the X chromosome

thinning starts in the crown

number of hair follicles and growth steps (cycle) remain constant
- BUT the anagen or growth stage is shorter (length of growth period is shorter)
- causes a shorter and thinner hair shaft

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20
Q

What is are the 3 key pathophysiologic features of alopecia pathogenesis

A
  1. Alteration in hair cycle development
    - anagen phase decreases but the telogen (shedding) phase remains the same length
    - anagen phase becomes so short that it does not reach the skin
  2. Follicular minimization
  3. Inflammation
    - sebacious glands and other secretions can build up overtime and cause this
    - not really studied
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21
Q

do males castrated before puberty or patients with androgen insensitivity develop alopecia?

A

No

22
Q

Which hormone plays a role in alopecia

A

Dihydrotestosterone
- binds to androgen receptor activating genes involved in hair follicles

23
Q

Which enzyme is used in alopecia? What are the 2 isoforms types in scalp hair follicles

A

5-alpha-reductase

2 isoforms
Type 1 in
- sebaceous glands
- epidermal and follicular keratinocytes
- dermal papillae cells
- sweat glands

Type 2 in (MAIN DRIVER)
- outer sheath of hair follicles
- Plus epididymis, vas deferens, seminal vesciles and prostate

24
Q

Is it common to have symptoms of BPH before age 50?

A

No

25
Q

What are risk factors of BPH

A
  • high levels of endogenous test, DHT, estradiol, insulin, inflammatory markers
  • Obesity
  • Diabetes
  • Lot of alcohol
  • Physical inactivity
26
Q

Prostate growth phase in men

A

Size of 1g until puberty

  1. grows to chestnut sized by 25-30
  2. Second growth spurt at age 40 where prostate can quadruple in size
27
Q

What fluids do prostates secrete (4)

A
  1. Citrate (nutrient source)
  2. Proteolytic enzymes to liquefy coagulated sperm
  3. Seminal plasmin
  4. Relaxin to enhance sperm motility
28
Q

How much do prostatic fluid contribute to total semen volume

A

1/3 (30%)
rest is
- seminal vesicles (65%)
- Testicles (5%)

29
Q

What are the 3 types of tissues in the prostate

A
  1. Epithelial tissue
    - produces secretions
  2. Stromal tissue or smooth muscle tissue
    - contains alpha-1 adrenergic receptors
    - normal prostate to stromal tissue ratio is 2:1, in BPH is 5:1
  3. Capsule
    - has fibrous connective tissue and smooth muscle
    - also contains alpha-1 adrenergic receptors
30
Q

Which hormone and enzyme play a central role in BPH

A

DHT
Type II 5-alpha-reductase

31
Q

What is the pathogenesis of BPH
2 components?
What causes them?

A

Static component
- Proliferation of the stromal (smooth) and epithelial cells of the prostate
- via DHT / 5-a reductase enzymes
- ANATOMIC enlargement
- PHYSICALLY blocks bladder neck and obstructs urinary flow

Dynamic component
- increase in smooth muscle tone in the prostate and bladder neck
- via alpha-adrenergic receptors

32
Q

What is the relationship between BPH and prostate cancer? how?

A

Strictly association and not causation
- BPH proliferation occurs in transitional or central zone
- prostate cancer occurs in the peripheral zone

33
Q

BPH pathogenesis progression (3)

A
  1. BPH
  2. BP enlargement
  3. BP obstruction
    - chronic bladder overfilling
34
Q

What are some obstructive symptoms in lower urinary tract symptoms?

A
  • slow urinary flow
  • intermittent urinary stream
  • straining to void
  • occasional mid-stream stoppage
  • post-void dripping
35
Q

What are some irritative symptoms in lower urinary tract symptoms?

A
  • increased daytime frequency
  • increased nocturia
  • increased urgency
  • increased retention
  • UTI
  • Urinary incontinence
36
Q

What are MANDATORY investigations for BPH (3)

A
  1. History
    - medical conditions
    - meds
    bladder contractility (anticholinergic agents)
    OR
    urinary outflow (sympathomimetic agents, phenylephrine ICU type meds)
  2. Urinalysis
    - to rule out infection
    - to detect presence of blood
  3. Digital rectal exam
    - normal prostate is firm and nontender
37
Q

What are RECOMENDED investigations for BPH (2)

A
  1. Symptom survey
    - american urological symptom score
  2. Prostate specific antigen PSA
    - measure prior to treatment with 5-alpha-reductase inhibitor
38
Q

What are the OPTIONAL investigations?

A
  • Serum creatinine
    (if high could be bladder obstruction)
  • Urine cytology
    (screen for bladder cancer or irritative symptoms)
  • Uroflow
    (if less than 15ml/sec)
  • Voiding diary
  • Post-void residual (PVR)
    concerning if over 200ml
  • Sexual function questionnaire
39
Q

What is the ED definition

A

Persistent failure to achieve a penile erection for a minimum of 3 months

40
Q

What are some causes of erectile dysfunction? (5)

A

Psychogenic
- performance anxiety

Organic
- vascular
- neurologic
- hormonal
- locale penile factors
- drug induced

41
Q

What drugs induce ED (7)

A
  • Antidepressants (SSRIs, MOAIs, TCAs)
  • Antihypertensives (beta-blockers)
  • Cardiac (digoxin amiodarone)
  • Diuretics
  • Hormones (corticosteroids, ketoconazole, antiandrogens)
  • H2RAs
  • Recerational drugs (alcohol, marijuana, cocaine)
42
Q

What 3 systems are affected in erection

A
  1. Vascular system
  2. Nervous system
  3. Hormonal system
43
Q

What is the physiology of the vascular system

A

Flaccid state
- arterial blood flow into and out of corproa cavernosa

Erect state
- decrease in venous outflow from the corpora
- inc in ARTERIAL flow into corpora via Ach vasodilation

44
Q

What is the physiology of the nervous system

A

Sacral nerve reflex arc
external stimuli integration vs hypothalamus

  • dopamine exerts erectile effects
  • Alpha-2-adrenergic is anti erectal effects
45
Q

What is the physiology of the hormonal system

A

testosterone stimulate sexual drive
- androgen receptors may increase NO nitric oxide

46
Q

What is it called if there is no organic cause and no response to psychogenic stimuli ?

A

psycjogenic erectile dysfunction

47
Q

How much % of cases is drug-induced erectile dysfunction responsible for?

A

10-25%

48
Q

What is ED a potential marker for?

A

arteriosclerosis
or CV disease

49
Q

What are Symptoms (2), signs (6), and lab values (3) for ED

A

Sx
- ED +/- decreased libido or other sexual disorders

Signs
- Low satisfaction with erection quality
- comorbidites (diabetes)
- signs of hypogonadism
- abnormall curved penis
- decreases pulses in pelvic region
- decreased anal sphincter tone

Tests
- testosterone
- Digital rectal exam
- Can also order PSA

50
Q

ED investigations (5)

A
  1. Sexual history
  2. Medical history (any vascular comorbidities)
  3. Medication history
  4. Physical exam
    - abnormal penile anatomy (curved or weak pulses)
    - signs of reduced nerve function via anal sphincter tone
  5. Lab tests (FBG, A1C, lipids)
    - serum testosterone if 50+ or if decreased libido

IPFC 3 Midterm 2 (7 decks)

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