Exam 6 (Renal and GU) Flashcards
Where is right kidney
Under liver.
L1-L4
Where is left kidney
T12-L3
Hilum
Central region where ureter, renal artery, and renal vein attach to kidneys
Ureter
Connects kidney to bladder constantly draining urine into bladder.
Exits kidney at ureteropelvic junction
Kidney cortex
Outer region.
URINARY GENERATION
Holds renal capsule, PCT, DCT, glomeruli
Kidney Medulla
Middle layer
URINARY GENERATION AND DRAINAGE
Consists of medullary pyramids, renal columns, loop. of henle, collecting ducts
Pelvis of Kidney
Inner central cavity
URINARY DRAINAGE
Empties into ureter
Blood flow through kidney
Bowman’s capsule –> Proximal tubule -> Descending loop of Henle –> Ascending loop of Henle –> Distal tubule
Nephron
Functional unit of kidney
Millions in each kidney.
Mostly in cortex
Bowman’s capsule
PCT
Loop of Henle
DCT
Collecting duct
Cortical Nephrons
85% of nephrons
In outer cortex
Loop of Henle short
Filter toxins and regulate Electrolytes
Less strict in filtration
Juxtamendullary Nephrons
15% of nephrons
Deep in cortex
Loop of Henle long so project into medulla
Reabsorb higher higher proprtion of glomerular FILTRATION rate.
Stimulate Na retention in states of low perfusion
Glomerulus
Filter
Primary site of urine formation
In Bowman’s Capsule
Bowman’s Capsule
Double walled funnel
Reservoirs for glomerular filtrate
PCT
Proximal convoluted tubule
High water permeability
2/3 glomelular filtrate reabsorbed
Reabsorbs NaHCO3, NaCL, K, glucose, AA, water
Adjusts pH
Loop of Henle
Allows water to pass from filtrate to interstitial fluid.
Ascending limb is water impermeable.
Descending limb is water permeable
Distal tubule
Selectively secretes and absorbs ions to maintain blood pH and electrolytes
Collecting ducts
Rabsorbs solutes and water from filtrate
Glomerular filtration barrier layers
- Fenestrated endothelium
- Glomerular basement membrane
- Podocyte slit diaphragm
Podocytes
Form slit diaphragm of glomerullus
Steps of Urine formation
- Glomerular Filtration
- Tubular reabsorption
- Tubular secretion
Why does the kidney excrete electrolytes
AWETBED
Acid-base balance
Water balance
Electrolyte balance
Removal of toxins
BP control
Erythropoietin production
D vitamin metabolism
ADH effect on kidney
Permeability of collecting tubules
Fluid regulation
Increases water reabsorption
Affects specific gravity
Aldosterone
Increases water and Na absorption by DCT.
Decreases potassium by increasing excretion.
Made and released by adrenal cortex
Calcitriol
Converted from calcidiol into calcitriol (active form of vitamin D) by kidney
Erythropoietin
Stimulates red blood cell production in bone marrow.
Released from kidneys when O2 is low.
Renalase
Metabolizes catecholamines, affects HR and BP
Renin
BP regulation via angiotensin
Released from kidneys when BP low to start RAAS pathway
Kidney role in glucose regulation
Catabolism of peptide hormones like insulin.
Can perform gluconeogenesis during times of fasting
How much cardiac output goes to kidneys
20-25%
Decreased perfusion to kidney
Stimulates RAAS system to increases blood pressure
Prerenal failure
Most common
Caused by decreased perfusion
Intrarenal failure
Direct damage to renal parnchyma
Postrenal failure
Obstruction
Types of acute renal failure
Prerenal
Intrarenal
Postrenal
Chronic Renal failure
Lasts longer than 3 months
Three phases of acute kidney injury
Oliguric - decreased output
Diuretic - increased output
Recovery - GFR normalizes
First phase of acute kidney injury
Oliguric
Decreased urine output
Edema
Decreased Na and water absorption
Hypervolemic
Weight gain
HTN
BUN and creatinine levels rise
Second phase of acute kidney disease
Diuretic
Increased urine output
Improved Na and water absorption.
Hypokalemia and hyponatremia can occur.
Hypovolemic
Weight loss
Dehydration
BUN and creatinin levels rise
Third phase of kidney disease
Recovery
Normal urine output
Recovery of GFR
Renal failure symptoms
Hyper/hypotension depending on phase
Dy mucous membrane
Poor skin turgor
Decrease/increase urine output depending on phase.
Mental status changes
Muscle aches
Nausea
First thing to look at to check for renal failure
Look at urine output and concentration of the urine (color)
First sign of kidney failure in lab
Albumin in the urine
First sign of kidney failure
Decreased urine output
Most accurate measure of GFR
Creatinine clearance because creatinine is filtered by glomeruli but not reabsorbed by tubules
Cast formation
Occurs in DCT and collecting ducts when Tamm-Horsfall protein is secreted by epithelial tube cells.
Tam Horsfall protein
Attracts adhesion of other tubular particles (cells, bile, hemoglobin, albumin, immunoglobulins).
Forms casts
Five main sections of nephrons
Glomerulus
PCT
Thin descending and thick ascending loop of Henle
DCT
Collecting duct
Diuretics that work in PCT
Carbonic anhydrase inhibitors
Osmotic diuretics
Diuretics that work in loop of henle
Loop diuretics
Diuretics that work in DCT
Thiazides
Diuretics that work in collecting duct
Potassium sparing diuretics
(Aldosterone inhibitors
Epithelial sodium channel antagonists)
What regulates bicarbonate reabsorption in PCT
Carbonic anhydrase
PCT drug targets
Carbonic anhidrase
SGLT2
Osmolality (Mannitol)
Thick ascending limb of Loop of Henle
High in NaCl reabsorption via Na/K/Cl cotransporter (NKCC2).
Diluted in lumen.
Impermeable
K transported through NKCC2
Loop of Henle drug target
N/K/CL cotransporter type 2 (NKCC2)
DCT
Distal convoluted tubule
NaCl reabsorption via Na/Cl cotransporter (NCC)
Dilutes tubular fluid
Results impermeability to water
DCT drug target
Na/Cl cotransporter
Thiazide diuretics
Collecting duct system
Final site of NaCl reabsorption
Determines Na concentration
Most important site of K secretion
Principal cells
In Collecting duct
Na reabsorption
K excretion
Water transport
No apical cotransporters
Regulated by aldosterone
Intercalated cells
In collecting duct.
Alpha does H secretion
Beta does bicarbonate secretion
Na and K relationship
Na transported back to blood via Na/K pump.
Na reabsorption happens more often than K secretion resulting in negative lumen.
Drives Cl back into blood.
Draws K into lumen from cell
Principal cells drug targets
Potassium sparing diuretics
Aldosterone receptor for potassium aldosterone antagonists
Epithelial Na channel for and epithelial Na channel antagonists
Acetazolamide
Carbonic anhydrase inhibitor
Decreases NaHCO3 rabsorpton
Attack at PCT
Carbonic anhydrase inhibitor mechanism
Acetazolamide
Blocks carbonic anhydrase thus inhbiting formation of carbonic acid.
Carbonic acid doesn’t dissociate into HCO3 and H.
No driving force for Na to be reabsorbed
Increased Na excretion in PCT
Acetazolamide uses
Carbonic anhydrase inhibitor
NOT used as diuretic
Glaucoma
Urinary alkalinization
Metabolic alkalosis
Acute altitude sickness
Acetazolamide adverse effects
Drowziness
Metabolic acidosis
Renal stones
K wasting
Neurotoxicity if renal failure
Mannitol
Osmotic diuretic
Solute that draws water out of cells.
Decreases intracranial pressure
Not really used as diuretic
Loop diuretics
Most effective (potent) diuretic against highest reabsorption of NaCl in thick ascending limb of Henle’s loop
Loop diuretics mechanism
Inhibits NKCC2 in thick ascending limb.
Decreases reabsorption of Na K Cl
Diminish lumen positive potential increasing secretion of K Mg and Ca.
Loop diuretics uses
Acute pulmonary edema.
Hyperkalemia
Hypercalcemia
Loop diuretic adverse effects
Acute hypovalemia (hypotension)
Hypokalemia
Hypomagnesemia
Ototoxicity
Hyperuricemia
Thiazides mechanism
Block Na Cl cotransporter in DCT decreasing Na and Cl reabsorption.
Low ceiling - at certain dose we don’t see increased effect
Thiazide uses
HTN
Heart failure
Prevention of Ca containing kidney stones caused by hypercalciuria
Thiazide adverse effects
Hypercalcemia
Hyperuricemia
Hyperglycemia
Hyperlipidemia
Hypokalemia
Hypomagnesemia
Hyponatremia
Hypovolemia
Potassium sparing diuretics
Antagonize effects of aldosterone by inhibiting Na reabsorption and inhibiting K excretion.
Aldosterone antagonists
Epithelial Na channel antagonists
Aldosterone antagonists method of action
Potassium sparing
Inhibit aldosterone receptor.
Decreases reabsorption of Na.
Decreases secretion of K
Spironolactone
Aldosterone antagonist
Potent inhibitor of aldosterone receptor
Used in acne and hirsutism.
Active at progesterone receptors
Eplerenone
Aldosterone antagonist
Less active on androgen and progesterone receptors
ENaC Antagonist mechanism
Potassium sparing diuretic.
Directly inhibits ENaC leading to decrease of Na reabsorption and decrease of K secretion.
ENaC antagonist
Potassium sparing diuretic
Mostly ued for K sparing effects, not diuretic effects
Ex. amiloride triametrene
Amiloride
ENaC that is not metabolized
Triametrene
ENaC that is metabolized.
Has very short half life
Potassium sparing diuretic uses
Edema
Hypokalemia
Heart failure
Resistant hypertension
Polycystic ovary syndrome
Potassium sparing diuretics adverse effects
Hyperkalemia
Spironolactone-gynecomastia
Triamterene (kidney stones)
Wolffian ducts
Become male reproductive organs
AKA mesonephric
Mullerian ducts
What become female reproductive organs
Reproductive embriology order in males
Primordial germ cells–> Spermatagonia + Sertoli cells–> Male gametes
Leydig cells
Produce testosterone
What causes differentiation in whether something ends up male or female
Presence of testosterone.
Decided at fertilization though
XY vs XX
Primordial germ cells
What males and females both start out as
Reproductive embryology order in females
Primordial germ cells –> oogonia –> granulosa and thecal cells –> estrogen and progestin in mature females
NO testosterone during this point so Wolffian duct degenerates
Complete Androgen Insensitivity Syndrome
46 XY DSD
Genotypically male but phenotypically female
No androgen receptors so testosterone can’t do its job.
Diagnosed by failure of menstrual cycle
Deficiency of 5 alpha-reductase
46 XY DSD
Genotypically male but phenotypically female
No 5 alpha reductase to convert testosterone into DHT (usable form)
Congenital Adrenal Hyperplasia
46 XX DSD
Genotypically female but phenotypically male
Impaired cortisol synthesis.
Virilization of female fetus
Excessive/deficient production of androgens/hormones
When do testes begin to enlarge
9-14
Male puberty
Testes inlarge
Spermatogenesis in seminiferous tubules
Scrotum and penis enlarge
INcreased testosterone leads to thicker hair, deeper voise, increased muscle strength
When does breast enlargement start
8-10
Female puberty
Breast enlargement
Ovarian cycle starts
ENlargement of uterus, labia majora, and labia minora
Widening of pelvis
Menarche
First period
Adrenarche
Surge of hormones and androgens leading to pubic and axillary hair before puberty
Precocious puberty
Early puberty
Gynecomastia
Enlargement of male breast
Occurs when estrogen levels are elevated in neonatal period or before normal male puberty.
Also can happen in elderly men
Testicle function
Secreting testosterone and make sperm
Epidymitis function
Store sperm
Vas deferens function
Expel sperm to urethra during ejaculation
Semeinal vesicles function
Produce fluid for nourishment for ejaculated sperm
Prostate gland function
Secretes acid phosphatase, contracts to deliver secretions into urethra, and liquifies semen until it gets to female reproductive tract.
Makes prostate specific antigen
Penis function
Urination and intercourse
Three phases of spermatogenesis
- Proliferation of spermatogonia
2.Generation of genetic diversity via miosis - Maturation of sperm
LH job in males
Stimulate Leydig cells to PRODUCE testosterone
FSH job in males
Stimulates Sertoli cells to secrete androgen binding protein that INCREASES testosterone.
Inhibin also secreted from sertoli cells that works in negative feedback against FSH
Phases of ejaculation
- Erection
- Emission
- Ejaculation
Erection
Sinusoidal spaces fill with blood
Emission
Spermatozoa and seminal plasma move into urethra
Ejaculation
Semen ejected from urethra
Stages of sexual response
- Excitement
- Plateau
- Orgasm
- Resolution
Excitement phase of sex
Penile erection
Vaginal lubrication
Plateau phase of sex
Vascular congestion
Engorgement of scrotum and labia
Orgasm phase of sex
Ejaculation in males
Pleasure
Rhythmic contractions of perineum
Resolution phase of sex
Penile falccidity
Vaginal relaxation
Refractory period in males
Ovaries
Where oogenesis occurs and eggs formed
Major source of sex steroids and hormones
Fallopian tubes
Transport ovum and sperm to fertillization
Transports zygote to uterus for implantatoin
Where does fertilization happen
Ampulla of Fallopian tube
Uterus
Supports growing fetus during preg.
Undergoes dramatic changes during menstrual cycle.
Growth through hyperplasia in preg.
Fundus
Corpus
Cervix
Vagina
Receive penis in intercourse
Temporarily retain sperm
Tube extending from cervix to vaginal opening.
Many mucus secreting glands for lubrication
Pelvic inflammatory disease
Caused by STD.
Usually chlamydia and gonorrhea
What increases risk of ectopic pregnancy
SCarred fallopian tubes.
Most common site of implantation in ectopic preg is ampulla
Fundus
In Uterus.
Area above opening to fallopian tubes
Corpus
Main body of uterus
Cervix
lower portion of uerus that extends and protrudes into vagina
Vulva
Collective name for female external genitalia Includes Lower 1/3 of vagina, labia, clitorus
Where does Oogenesis occur
Ovaries
Oogenesis
Forming of eggs
OOgonium –> 1º Oocyte –> 2º Oocyte –> Ovum
Graafian Follicle
Dominant Follicle
Emerges and LH surge makes it a secondary Oocyte.
Bursts and ruptures during period
When is Oogenesis complete
Fertilization
Becomes Ovum
Menstrual cycle phases
- Follicular- 1-14
- Ovulatory - 13-15
- Luteal - 15-28
Follicular phase
Days 1-14
Day 1 is first day of bleeding
Primary follicles develop
Dominant follicle emerges
Ovulatory phase
Days 13-15
LH surge and increased estrogen
Ptimary oocyte completed meiosis I
Dominant follicle rupture causing ovulation.
Oocyte released
Best time to get pregnant
Days 12-14
When is ovulaton
Day 14
Luteal Phase
Days 15-28
Corpus luteum formed
If no preg corpus luteum degenerates.
If preg continued progesterone secretion essential.
Hydatidiform mole
Benign molar pregnancy
Incompatible with life.
Looks like cluster of grapes
Implantation
Fertilized egg develops 6-7 days prior to implantation.
Now a blastocyst
Endometrium develops
3 stages of implantation
1.Apposition - formation of loose connection in endometrium
2.Adhesion - microvilli extend from cell
3. Invasion - Embryo becomes completely embedded in endometrium of uterus
Placenta function
Transport glucose, LDL, AA, large molecules to fetus between maternal and fetal circulations.
Secretion of hormones to maintain function
Placenta hormone secretion
Estrogen for growth of uterus starts 12 weeks in.
Progesterone starts at 9 weeks in
Progesterones for maintaining endometrium and reducing uterine contractions to prevent premature birth.
Progesterone drops at the end of preg to let birth happen
Estrogen drops at end to allow milk let down
Placental peptides examples
Human chorionic gonadotropin (hCG)
Human chorionic somatomammotropin hormone (hCS)
Start off high at begining of preg. Drop off at the end
hCG
Human chorionic gonadotropin
Placental peptides
Keeps corpus luteum from degenerating.
Allows ocntinued progesterone to be secreted for early preganncy until placenta can take over making and secreting progesterone
hCS
Human chorionic somatomammotropin hormone
Plancental hormone
Stimulates production of fatty acid and ketones for energy for fetus and placenta
Promotes mammary gland development
Creates state of insulin resistance in mother to promote availability of glucose for fetus
What keeps labor going (parturition)
Prostaglandin and oxytocin
Phase 0 of parturition uterine activity
Majority of pregnancy with uterus inactive/relaxed
Phase 1 of parturition uterine activity
Cervix dilates and amniotic fluid ruptures (water breaks).
False contractions
Phase 2 of parturition uterine activity
Fetus is expelled from uterus
Phase 3 of parturition uterine activity
Placenta is birthed
What is breast milk made of
Lactose
Triglycerides
Protein
Colostrum
Liquid gold.
Very nutritious breast milk made after first few days of parturition
What hormone does breast milk production
Prolactin
What stimulates milk let down
Oxytocin. Works in positive feedback loop.
When does milk production start
about 2 days after parturition because estrogen and progesterone were just very high
Suckling reflexes
Prolactin and oxytocin stimulated by baby sucking on breast. Positive feedback
What happens to other organ systems during preg
Blood volume and coagulabibity increases\
Alveolar ventilation increases
GFR increases
Nutritional demands increase
Suppression of immunity
Overactive bladder meds
Antimuscarinics
beta-3 adrenergic agonists (-begron)
Benign prostatic hyperplazsia drugs
alpha-1 adrenergic agonist (-osin)
5-alpha reductase inhibitors (-asteride)
Overactive bladder
Frequent strong urge to urinate even when not really necessary
Goals of overactiv bladder meds
Decrease urge frequency
Increase voided volume
Antimuscarinic meds mechanism
Block M3 receptors on bladder.
Decreases freq of bladder contractions and increases capacity
Most selective antimuscarinics
DariFENACIN
SoliFENACIN
Fewer adverse effects
Trospium
Antimuscarinic
Doesn’t undergo CYP450 metabolism.
So good option for someone in liver failure
Does not cross BBB so fewer CNS effects
Antimuscarinic adverse effects
Dry mouth
Constipation
Blurred vision
CNS impairments
Ocybutyynin
Antimuscarinic
OTC patch
Gel
Beta-3 adrenergic agonist mechanism
Bind and activate B3 adrenergic receptors.
Increases cAMP
Relaxes detrusor muscle increasing bladder capacity
Beta-3 adrenergic agonist adverse effects
Urinary retention
UTI
Mirabegron increases BP inhibits CYP2D6, and causes angiodema
Benign prostatic hyperplasia (BPH)
Non-malignant enlargement of prostate
Common in men over 60
Increase in size (static) and/or tone (dynamic)
alpha-1 adrenergic antagonist
-osin
address tone of prostate
alpha-1 adrenergic receptors subtypes locations
A - prostate
B - prostate and vasculature
D - vasculature
alpha-1 adrenergic antagonist mechanism
Block prostatic alpha-1A and alpha1-B this is in prostate and blood vessels
Adrenergic antagonis selective for alpha 1A
Silodosin
Tamsulosin
no Z in name
alpha-1 adrenergic receptor antagonist adverse effects
Dizziness
Orthostatic hypotension
Tachycardia
Drowsiness
Inhibition of ejaculation
Retrograde ejaculation (shooting blanks)
5-alpha reductase inhibitors
-asteride (five asteroids coming to blow up prostate to reduce size)
Address size of prostate
5-alpha reductase inhibitor mechanism
Irriversibly inhibits alpha-5 reductase.
Testosterone not turned into usable form DHT.
Decreased growth signaling
Improved urine flow
5-alpha reductase inhibitor Adverse Effects
Risk of prostate cancer.
Decreased ejaculate and libido
Erectile disfunction
Oligospermia
Teratogenic
Day 2-7
FSH increase
Day 7
Estrogen increase
Day 14
LH FSH surge in response to estrogen causing ovulation
Day 15
Ovulation.
Progesterone increases
Day 21-28
Estrogen and progesterone drop if no fertilization
Day 28
Wthdrawal of estrogen and progesterone
Estrogen use as contraceptive
Blocks GnRH production from hypothalamus and FSH production from ant pit.
Prevents follicle development
Progestin use as contraceptive
Blocks GnRH production from hypothalamus and LH production from ant pit.
No LH surge preventing ovulation half the time
Thickens cervical mucus to inhibit sperm migration.
Thins endometrium
What are the type of hormonal contraceptive
Estrogen and progestin
Or just progestin
Most common estrogen component in oral contraceptiv
Ethinyl estradiol
What is the design of taking birth control pills
21 active tablets
7 placebo tablets
mimic the natural process
Is combined pill or progestin only pill more effective
They are the same.
What is the main mechanism of progestin contraceptive
Thinning of endometrium
Thickening of cervical mucus
What is the main mechanism of combined (estrogen and progestin) contraceptive
Preventing ovulation (does it every time)
Combined oral contraceptives
Estrogen + Progestin
Mono bi or triphasic
Cyclic
Cyclic combined contraceptives
Traditional
Take active pills for 21-24 days.
Placebo for 7-4 days
24/4 recomended over 21/7 because can use lower estrogen content
Extended cycle combined contraceptive
Active pill for 84 days.
7 days of placebo.
Withdrawal bleeding every three months
Continuous cycle combine contraceptive
Actie pills taken every day
No withdrawal bleeding
No medical need for menstruation with oral contraception
Write “for continuous use” on Rx
Is natural or synthetic progesterone better on gettig past first past metabolism
Synthetic
What progestins have high affinity for androgen receptors
Levonorgestrel
Norgestrel
What progestins have low affinity for androgen receptors
Drospirenone
What progestins have high affinity for progesterone receptors
All of them
Estrogen negative feedback
INhibits GnRH LH and FSH.
Causing no ovulation.
Most important mechanism in combined contraceptives
What stimulates menstrual bleeding
Withdrawal of progestin
Non-contraceptive benefits of oral contraceptives
Reduction of dysmenorrhea
Reduction in pelvic pain from endometriosis
Reduction in premenstrual syndrome
Reduction in endometrial cancer
Reduction of acne
Reduction of hirsutism
Venous thromboembolism
Blood clots
Caused by estrogen effect on clotting cascade
Caused by combined oral contraceptives
Who should not be prescribed combined with oral contraceptive
35 yo smoker
CV disease
Hx of breast cancer
Migraine with aura
You CAN give these people progestin-only pill instead
Progestin-only pill
Supppresses GnRH and LH
Norethindrone
Older Progestin-only pill
Must be taken same time each day.
All tablets are active
Short duration of action
Drosperinone
Newer Progestin-only pill
Should be taken same time each day but more forgiving because have a longer half-life.
4 placebo pills
Drosperinone adverse affects
Hyperkalemia
Hyperglycemia in diabetics
Don’t give to pts with adrenal or renal problems.
Don’t give to pt with hx of cervical cancer
Norgestrel
Progestin-only pill
No rx required (OTC)
Benefits of progestin only pill
No weight gain
No increase in headache
Safe for CVD HTN who can’t take combined pill
Progestin only pill adverse effects
Unscheduled bleeding
Increased prevalence of follicular ovarian cysts.
Drosperinone can cause hyperkalemia
IUDs as emergency contraception
Copper inserted within 120 hours
Hormonal inserted within 5 days
Plan B
Emergency contraceptive
Singl high does of levonorgestrel
Progestin
Must be taken within 72 hours
Less efective in women >165 lbs
Ulipristal
Prescribed emergency contraception.
Binds to progesterone receptor inhibiting or delaying ovulation.
Must be taken within 5 days.
Less effective in women >195 lbs