MCB 135K Discussion April 27, 2005

Topics Urinary System Male Reproductive System Female Reproductive System

Table 19-1 Major Functions of the Kidney Water and electrolyte regulation Metabolic products excretion Hydrogen ion excretion and maintenance of blood pH Endocrine functions: Renin-angiotensin secretion (blood pressure) Vitamin D activation (Ca ++ metabolism) Erythropoietin secretion (hematopoiesis)

Table 19-2 Common Renal Problems in the Elderly Renal Failure Impaired drug excretion Urinary tract infections Hypertension Miscellaneous disorders: Tuberculosis Nephritis Diabetes, etc.

Table 19-3 Some Signs of Renal Failure Generalized edema Acidosis Increased circulating non-protein nitrogen (urea) Increased circulating urinary retention products

Table 19-4 Selected Causes of Acute Renal Failure PRE-RENAL: Loss of body fluids Inadequate fluid intake Surgical shock or myocardial infarction RENAL: Drug toxicity Immune reactions Infectious diseases Thrombosis POST-RENAL: Urinary tract obstruction

Table 19-6 Drugs and the Aging Kidneys Questions: Is the drug excreted primarily by the kidney? How competent are the kidneys? What are the side-effects? What are the consequences of drug toxicity when the kidney is impaired? Etiopathology of Renal Drug Toxicity: High renal blood flow Increased drug concentration and accumulation in kidney Increased hepatic enzyme inhibition in the elderly Increased autoimmune disorders in the elderly

Table 19-8 Age-Related Changes Contributing to Incontinence In Females Estrogen deficiency Weak pelvic floor and bladder outlet Decreased urethral muscle tone Atrophic vaginitis In Males Increased prostatic size Impaired urinary flow Urinary retention Detrusor muscle instability

Anatomy of the Male Reproductive Tract In humans the principal reproductive organ is the brain In addition to the brain, the male reproductive system consists of the: TESTIS Primary sex organ suspended outside of the body in the scrotum Secondary male sex organs include: EPIDIDYMIS, VAS DEFERENS, EJACULATORY DUCTS which carry sperm to the urethra SEMINAL VESISCLES, PROSTATE, & BULBOURETHRAL GLANDS which secrete seminal fluid PENIS with URETHRA through which flow both urine and semen

A simplified version of the male reproductive endocrinology: The hypothalamus releases GnRH into the circulatory system and, through blood, directly into the pituitary. GnRH triggers the release of the pituitary LH and FSH that stimulate the testes to testosterone secretion and sperm production.

the GERM CELLS or GAMETES, involved in fertilization. the INTERSTITIAL CELLS of LEYDIG that secrete testosterone, the major androgen the SERTOLI CELLS with secretory and reproductive functions The testis, the male primary reproductive organ, contains three types of cells, all necessary for reproduction:

With Age: On the average, the male reproductive function remains normal (or only slightly diminished in some individuals) until advanced old age (80+ years) when it decreases Subtle changes include: GnRH Sensitivity of androgen secretion to LH Sensitivity of negative feedback between GnRH and LH

Table Normal Aging of the Prostate After age 40: Outer regions: Atrophy of smooth muscle and proliferation of connective tissue Flattening of secretory epithelium Inner region: Increase in the number of cells present (hyperplasia) After age 60: Slower, but more uniform atrophy of the prostate Accumulation of prostate concretions

Table The Prostate and Testosterone The healthy prostate is dependent on androgens for growth In the prostate: testosterone  dihydrotestosterone (DHT) The enzyme catalyzing this reaction is 5-  -reductase DHT stimulates growth of the prostate

Treatment of Prostate Cancer Depends on Life expectancy Overall health status Personal preferences Size of the prostate State of disease Treatments include: Watchful waiting Surgery Radiation Therapy Hormonal Therapy Cryotherapy **PSA controversary pp. 353, 354**

Ovary Characteristics Ovaries –Contain germinal cells –Contain endocrine producing cells Thecal Granulosa –Determine secondary structures and sexual characteristics

Hypothalamus Ovaries Pituitary E2, P GnRH FSH, LH

Normal Female Hormone Patterns

Hormonal Changes From Aging Gonadotropins: –LH Change to pulsatile pattern:  Duration,  Frequency –FSH “Monotropic FSH  1 st Noticed prior to any change in cycle length Ovarian Steroidal Hormones –Estrone levels  early in the cycle in older ovulatory women Possible due to LH/FSH alterations –Eventually, H-P-G axis is unable to generate LH surge needed for ovulation

Ovarian Structural Changes Abnormalities in Older Oocyte –Change in microtubule and chromosome placement at the second metaphase of meiosis –May be linked to increased aneuploidy seen in offspring of older women Declining Follicular Reserve –2 Million Primordial Follicles during fetal development –Declines to 1 million at birth and 250,000 by puberty –Primordial Follicles develop to primary and secondary follicles independent of hormone status –In the absence of LH/FSH, follicles undergo atresia –Once follicles are depleted, ovarian hormone production declines

Menopause Symptoms Hot Flashes –Most common reported symptom –70-80 % of women report signs of hot flashes –This rate increases in women with oopherectomy and thin women that smoke –Asian women have much lower rate % Reported Possibly due to genetics, diet, lack of reporting

Physiological Characteristics of Hot Flashes Sweating Increased Skin Conductance Increased Core Body Temperature Increased Metabolic Rate Increased Skin Temperature Hot flashes appear to be the result of noradrenergic control independent of estrogen regulation – ERT alleviates the symptoms of hot flashes –Adrenergic receptor agonists also show promise for treatment

Effects on Non-Reproductive Steroidal Targets Skin –Thinning of epidermis –Atrophy of sebaceous glands –Increased sensitivity to temperature, humidity, and trauma Bladder –General Atrophy Results in urinary incontinence Hair –Body hair undergoes redistribution

Menopause and Non-reproductive Targets Skeletal System –Osteoporosis Decreased bone mass following menopause that appears to be the result of declining estrogen level Central Nervous System –Psychological Anxiety/Depression –Cognition/Memory Cardiovascular System –Possibly due to role of estrogen in lipid metabolism