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Bio217 Fall 2012 Unit VIII

Bio217: Pathophysiology Class Notes  Kidneys (2) Professor Linda Falkow ◦ Retroperitoneal ◦ Unit VIII: Urinary (Renal) System Disorders ◦ Adipose capsule and ◦ Disorders ◦ Hilum  (2)  (1) Chapter 28: Structure & Function of Renal & Urologic Systems  (1) Chapter 29: Alterations of Renal & Urinary Tract Function Chapter 31: Structure and Function of Reproductive Systems Chapter 32: Alterations of the Reproductive Systems Structures of

• 1.2 million per • Functional unit of the kidney – Cortical nephrons • – Juxtamedullary nephrons • Medulla • Pyramids • Parts of • Calyces – (= + Bowman capsule) – Renal – Minor and major • Proximal (pct) • • • Distal tubule (dct)

Structures of the Kidney Nephron

• Glomerular membrane – passes through the three layers and forms the filtrate

Nephron Nephron

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• Juxtaglomerular apparatus – Juxtaglomerular cells ( ) – (sense changes in Na+)

– Renin- pathway: reg. BP • Decr. blood vol. or decr. Na+  incr. renin  Angiotensin I  Angiotensin II  (incr. of Na+ and H2O) Nephron Juxtaglomerular Apparatus

• Urinary Bladder – – Trigone – Micturition reflex

• Urethra – Internal and external sphincters – 3 to 4 cm in females – 18 to 20 cm in males Structures of Urinary System Urinary Bladder and Urethra

• Receive 1000 to 1200 mL of blood/min. • Neural regulation • Glomerular filtration rate (GFR) • • – Renin-angiotensin system – Tubuloglomerular feedback – Aldosterone – ADH (conserves /incr. water reabsorption)

Renal Blood Flow Renal Blood Flow

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• Filters plasma

• Reabsorbs and secretes – Tubular reabsorption and • Forms a filtrate of -free fluid

• Regulates filtrate to maintain fluid volume, , and pH Renal Blood Flow Nephron Function

• system • Glomerular filtration – Contributes to production of concentrated – Net filtration pressure • Glomerular oncotic/hydrostatic pressure • Bowman capsule oncotic/hydrostatic pressure

– Filtration rate • 180 L/day Concentration and Nephron Function Dilution of Urine

• Aldosterone • Antidiuretic (ADH) • Urinary tract obstruction • Atrial natriuretic (ANP) – interference with flow of urine at any site – produced by RA, when RA press. increases, along urinary tract inhibits secretion of renin – Obstruction can be caused by anatomic or • functional defect – enhance urine flow (by disrupting Na+ • Obstructive uropathy – changes in reabsorption and decr. ECF vol. urinary system due to obstructions (anatomic) Concentration and Urinary Tract Obstruction Dilution of Urine

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• UTI - inflammation of urinary epithelium caused by bacteria • Acute cystitis • Interstitial cystitis • Acute and chronic

Urinary Tract (UTI) Urinary Tract Obstruction

Acute cystitis • Interstitial cystitis ◦ Cystitis is an inflammation of the u.b. – Nonbacterial infectious cystitis ◦ E. coli most common cause – Manifestations

• Most common in women 20 to 30 years old ◦ Manifestations • Bladder fullness, frequency, small urine vol.,  Frequency, dysuria, urgency, and lower abdominal chronic pelvic pain and/or suprapubic pain • Immunocompromised (undergoing chemo or radiation therapy) ◦ Treatment – Treatment  Antimicrobial therapy, increased fluid intake, • No single treatment effective, symptom relief avoidance of bladder irritants, and urinary analgesics (UTI) Urinary Tract Infection (UTI)

• Pyelonephritis – Acute pyelonephritis • Acute infection of the renal pelvis & – (urine reflux up into kidney), E. coli, Proteus, Pseudomonas

– Chronic pyelonephritis • Persistent or recurring episodes of acute pyelonephritis that to scarring

• Risk of chronic pyelonephritis increases in individuals w/ Normal size- scarring on Shrunken size - scarring renal and some type of obstructive upper surface pathologic condition Chronic Pyelonephritis Urinary Tract Infection (UTI)

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• Mechanisms of injury • – Immune response - deposition of antigen- – Inflammation of the glomeruli (typically after a antibody complexes in glomerular strep infection) • Immunologic abnormalities (most common) • Drugs or – Formation of antibodies against the • Vascular disorders glomerular  • Systemic diseases break down cells  incr. permeablility • Viral causes – Most common cause of end-stage renal failure Glomerulonephritis Glomerular Disorders

• Acute poststreptococcal glomerulonephritis

• Rapidly progressing glomerulonephritis (RPGN) – Antiglomerular basement membrane disease (Goodpasture syndrome) – rare

• Chronic glomerulonephritis Glomerulonephritis Kidneys are small and have granular external surface Glomerulonephritis

• Uremia Chronic renal failure (CRF) = accumulation of N-wastes and metabolic • toxins in plasma -progressive, irreversible loss of renal function that affects nearly all systems

– Symptoms: confusion, GI complaints, • Stages fluid in , infection –Chronic renal insufficiency (GFR 20-35% of normal) – Describes clinical manifestations of CRF –Chronic renal failure (GFR 20-25% of normal) (chronic renal failure) –End-stage renal failure (GFR <20% of normal) Chronic Renal Failure

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• CRF due to: – Glomerulonephritis – Chronic infections (pyelonephritis or TB) – Congential (polycystic disease) – Vascular (HT or nephrosclerosis) – Obstructions (renal calculi) –

Chronic Renal Failure

• Alterations seen in following systems: Imbalances in following factors: – Musculoskeletal • and uremia – Cardiovascular and pulmonary • and – Hematologic • Fluid and balance – – and water balance Immune – and balance – Neurologic – balance – Acid-base balance Chronic Renal Failure Chronic Renal Failure

• 1. Which is an abnormal substance of urine? – A. Urea C. NaCl –Gastrointestinal – B. D. Creatinine • Alteration in protein, carbohydrate, and lipid • 2. The presence of albumin in urine would indicate damage to: – A. Glomeruli C. pyramids –Endocrine and reproduction – B. Collecting ducts D. None of the above –Integumentary • 3. GFR is regulated by – A. ANS C. Renin-angiotensin system – B. ANF D. All of the above Chronic Renal Failure Concept Check

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• 4. An increase in permeability of the dct and cd Matching: is due to: • ___ 6. acute cystitis a. Infection of renal pelvis & – A. Decrease in ADH production interstitium – B. Increase in ADH • ___ 7. uremia b. Inflam. that is most common – C. Decrease in osmolality cause of end-stage renal – D. Increase in water content in blood failure • ___ 8. glomerulonephritis c. Renal failure w/ elevated blood urea and creatinine • 5. UTIs occur: • ___ 9. pyelonephritis d. U.b. inflam. ranging from – A. Only in the kidneys hyperemic mucosa to – B. Anywhere but the kidneys necrosis of u.b. wall – C. Anywhere in the urinary system

Development of the Reproductive System Structure and Function of the • Dependent on sex hormones Reproductive Systems – Males— – Females—, FSH, and LH Chapter 31 & Alterations of the Reproductive Systems Chapter 32

Female Reproductive System Internal Genitalia

• External genitalia (vulva) • Vagina – Mons pubis • Uterus – Labia majora – Cervix – Labia minora • Fallopian tubes – Clitoris • Ovaries – Vestibule

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Uterine Position Internal Genitalia

Ovary Follicle Development

Female Sex Hormones Menstrual Cycle • • Menarche – (E2)- 95% produced by ovaries • - remainder by & placenta • Menopause () • Phases – Estrone – Menstruation (menses) – Estriol – Follicular/proliferative phase • – from corpus luteum – Luteal/secretory phase • Androgens – small amt. from ovaries & – Ischemic/menstrual phase adrenal cortex

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Menstrual Cycle Menstrual Cycle

• Ovarian cycle • Uterine phases • Vaginal response • Body temperature change – BBT (basal body temp.) biphasic – Follicular phase = ~98oF – Luteal phase ~ 0.4 -1.0 oF.elevation

Male Reproductive System

• External genitalia – Testes • Produce gametes and sex hormones – • – Scrotum – Penis • Glans and prepuce

Male Reproductive System Spermatogenesis • Internal genitalia • Spermatogonia – Ducts • Primary spermatocytes • Vas deferens and ejaculatory duct – Accessary Glands • Secondary spermatocytes • • Spermatids • Prostate gland • Bulbourethral glands • Sertoli cells (Sustentacular cells)

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Disorders of the Female Reproductive Male Sex Hormones System • Androgens • Hormonal and menstrual alterations – Primary androgen—testosterone – Primary dysmenorrhea (painful menstruation) • Painful menstruation associated with – Produced mainly in (interstitial cells of) release in ovulatory cycles Leydig cells of testes – Secondary dysmenorrhea – Testosterone • Painful menstruation related to pelvic • Sexual differentiation (endometrioisis, PID, fibroids) • Urogenital system dev. – Pathophysiology • Nervous and skeletal tissue dev. • Excess PGF from endometrium;  GI upset, headaches, • Libido syncope – Treatment: Hormones, PG inhibitors, exercise, heat

Hormonal and Hormonal and Menstrual Alterations Menstrual Alterations • Primary amenorrhea • Secondary amenorrhea – Absence of menstruation by age 14 – Causes (& no secondary sex characteristic dev. by age 16) – Pathophysiology: • Pregnancy (normal) • Dysfunctional H-P-O axis; congenital or hypoplasia • Dramatic weight loss of uterus; genetic (Turner’s syndrome XO) –Malnutrition or excessive exercise • Secondary amenorrhea – Absence of menstruation for three or more cycles or 6 – Anovulation months in women who have previously menstruated – Hirsutism (increased testosterone)

Hormonal and Amenorrhea Menstrual Alterations • Abnormal uterine bleeding – Menstrual irregularity – Dysfunctional uterine bleeding

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Infection and Inflammation • Pelvic inflammatory disease (PID) Pelvic Inflammatory Disease (PID) – Acute inflammatory disease due to infection – May involve any organ of reproductive tract • Salpingitis (infalm. of fallopian tubes) • Oophoritis (inflam. of ovaries) – STDs migrate from vagina to the upper genital tract – Polymicrobial infection (due to gonorrhea or chlamydia)

– Can to infertility, ectopic pregnancy, , septic (death)

Pelvic Inflammatory Disease (PID) (Salpingitis) Leiomyomas (benign fibroid tumors) - dev. from SMC

Note- swollen fallopian tubes, adhesions on ovaries

Benign Growths and Female Reproductive Proliferative Conditions • Cervical cancer (2% of in women) – Cervical (CIN – cervical intraepithelial • Endometriosis neoplasia – precancerous) – Presence of functioning endometrial tissue or implants outside the uterus (retrograde menses) – Invasive carcinoma of the cervix – Responds to hormone • Risk factors fluctuations of the menstrual – HPV and HIV cycle – Multiple sexual partners – Occur mostly in abdominal & pelvic cavities – Poor nutrition and smoking • Vaccine (2006) – Gardisil (Merck) against HPV 6,11,16,18 • Pap smear – screening test

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Cervical Cancer Female Reproductive Cancer

A: progressive degrees of CIN • Ovarian cancer (> 5% of all female cancer deaths) (cervical intraepithelial neoplasia) • Cause – unknown; incr. risk with age, family

history (breast or ovarian cancer) • Pathophysiology: B: Normal mulitparous cervix – Arise from epithelial cells (on outside of ovary, or stroma)

– Associated with BRCA genes (breast cancer)

C: CIN Stage 1 • Symptoms: & swelling (ascites) (cancer only in cervix) • : pelvis, colon, , pleura

Disorders of the Testis Disorders of the Testis –Orchitis Cancer of the testis • Among the most curable of cancers (>95% cure) • Acute inflammation of the testis • Common in men between ages 15 and 35 • Complication of a systemic disease or • Causes painless testicular enlargement related to epididymitis – Risk factors • Mumps most common cause • History of Crytorchidism (undescended testes) • Abnormal dev. of testes • Klinefelter (XXY) • History of testiscular cancer

Disorders of the Prostate Gland Disorders of the Prostate Gland • Cancer of the prostate • Benign prostatic hyperplasia (BPH) – Accounts for 29% of all cancers in males – Enlargement of the prostate gland – Prostatic cancer is asymptomatic until adv. stages – Symptoms associated with urethral – Symptoms are similar to BPH compression • Pathophysiology – Relationship to aging – 95% of neoplasms are adenocarcinomas – Evaluation – Related to hormone use – T  DHT and estradial (in animal studies: both  • Digital rectal exams carcinogenic effect) • Prostate-specific antigen (PSA) monitoring – Action of IGF ( growth factor) potent

mitogen (increase cell prolif. and decr. apotosis) :. Cancer cell lives and multiplies

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Disorders of the Prostate Gland Benign Breast Lesions

• Cancer of the prostate • Nonproliferative breast lesions – Dietary factors (high sat. fat, incr. calcium levels  – Fibrocystic changes (FCC) decr. Vit. D which protects against prostate cancer, low fiber and complex CHO, incr. protein • Proliferative breast lesions without atypia – Epithelial hyperplasia – Hormones (anabolic ) – Florid hyperplasia – Vasectomy (possibly due to elevated androgens, – Sclerosing adenosis antisperm antibodies) – Complex sclerosing lesion – Chronic inflammation – Papillomas – Familial factors (5-10%)

Breast Cancer Breast Cancer

• Most common cancer in American women • Leading cause of death from ages 40 to 44 • Second most common killer after cancer • Black women more likely to die from it

Breast Cancer Breast Cancer • Manifestations – Painless lump, dimpling of skin, • Reproductive factors (early 1st pregnancy lowers risk) • Pathophysiology: • Hormonal factors (ovarian androgen excess, HRT incr. risk) – 70% arise from ductal (glandular) epithelium • Environmental factors and lifestyle – Genetic alterations of DNA, chromosomes, – Radiation suppression of apoptosis – Diet (high intake fruits,veg., whole grains, low fat) – 1/3 are hormone dependent (Progesterone or – Chemicals (xenoestrogens – mimic estrogens, found in pesticides, positive) plastics, detergents, drugs) (PCBs, DDT) • Treatment • Physical activity – Based on stage of cancer • Familial factors and tumor-related genes – , radiation, chemotherapy, hormone therapy, biologic therapy and marrow transplantation

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Disorders of the Male Breast Chlamydial Infections

• Gynecomastia • Chlamydia (bacterial) – Overdevelopment of the breast tissue in a male – Infections caused by Chlamydia trachomatis – Results from hormone alterations – Most common STI in the United States • Idiopathic and system disorders, drugs, or neoplasms – Obligate, gram-negative, intracellular bacterium

• Male breast cancer – Most commonly seen after age 60 – Tumors resemble carcinomas of breast in women – Crusting and nipple discharge are common clinical manifestations

Sexually Transmitted Sexually Transmitted Urogenital Infections Viral Infections • • Human papillomavirus (HPV) – Treponema pallidum – 120 different types of HPV • Corkscrew-shaped, anaerobic bacterium • 30 serotypes are unique to stratified squamous that cannot be cultured in vitro epithelium • Infects any body tissue • Divided into high-risk and low-risk serotypes • Syphilis becomes a systemic disease shortly after infection. – HPV is a nonenveloped, circular double-stranded DNA –Maternal-fetal transmission virus

Sexually Transmitted Sexually Transmitted Viral Infections Parasitic Infections • Genital herpes • Trichomoniasis – Two serotypes – Caused by T. vaginalis • Herpes simplex virus type 1 • Anaerobic, unicellular, flagellated, parasitic • Herpes simplex virus type 2 protozoan – 80% of initial and 98% of recurrent infections are type 2 – Adheres to and damages squamous epithelial cells – Transmitted through contact with a person • Urethra, vagina, and Skene and Bartholin glands who is shedding the virus in a secretion or from a peripheral lesion or mucosal surface – Accounts for 25% of infectious vaginitis cases

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Sexually Transmitted Sexually Transmitted Parasitic Infections Parasitic Infections • Pediculosis pubis • Scabies – Caused by the crab louse Phthirus pubis – Caused by the adult female itch mite, – Transmitted primarily by intimate sexual Sarcoptes scabiei contact or contact with infected bed linens or clothing – Transmission of scabies requires prolonged close skin-to-skin contact – A crab louse has a 25- to 30-day life cycle • Stages: egg or nit, three nymphal stages, • Typically occurs between family and an adult stage members or sexual partners

Concept CHECK • 3. Cells that produce testosterone: – A. Interstitial cells • 1. Progesterone – B. Testicular endocrine cells – A. Stim. lactation – C. Sustentacular cells – B. Incr. uterine tube motility – D. Spermatogonia • 4. The function of testosterone: – C. Thins the endometrium – A. Dev. Of male gonads – D. Maintains the thickened endometrium – B. Bone and muscle growth – C. Influence sexual behavior – D. Growth of testes • 2. The ovaries produce – E. All of the above – A. Ova, estrogens, • 5. Acute PID – A. Mainly affects males – B. Ova only – B. Is usually caused by viruses – C. Ova and estrogens – C. Never causes peritonitis – D. Testosterone & semen – D. May cause infertility or tubular pregnancy

• 6. Endometriosis – A. Has ectopic endometrium responding to changing hormone levels of the menstrual cycle – B. Occurs mainly in the pleural cavity – C. Causes infertility in most women – D. Does not occur after treatment

• 7. The infectious cause of orchitis is – A. Streptococci – B. Gonococci – C. Chlamydial organisms – D. Mumps virus

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