Genitourinary and renal systems:

Renal function

• >1100 mL of blood processed via kidneys each minute
• ONLY 1-2 liters excreted as urine each day, 99% reabsorbed
• Kidneys are only 0.4% or body weight but require 20-25% of cardiac output(amt of blood ejected from the heart)
• Filters substances to maintain fluid and electrolyte balance
• Detoxifies and eliminates waste
• Stimulates the production of RBCs
• Regulates vitamin D and Calcium levels

Renal blood supply

• Renal artery comes direcrtly off the aorta

• subdivisions of the renal artery form afferent arteries supply blood to glomerulus

• other subdivisions supply blood to tubular strucutres origninate from efferent arteriole

• renal veins- return blood to inferior vena cava

• during instances of low blood flow to the kidney, blood is dispersed toward the medulla and away from the cortex to concentrate urine

Renal veins return blood to?

inferior vena cava

What is the functional unit of the kidney?

nephron

What is the nephron?

Functional unit of kidney
• Up to 1 million in each kidney
• No ability to regenerate—lose 10% each decade after age 40
• Contains vascular(brings blood) and tubular(holds urine) components
• Contains:
a. glomerulus
b. proximal convoluted tubule
c. loop of henle
d. distal convoluted tubule
e. collecting duct

What is being described here?

• Site of filtration

• Clump of capillaries enclosed in a capsule called Bowman’s Capsule

• Unique, HIGH pressure system (Study hint: uses capillary filtration pressure to push out the filtrate)

• H20 soluble nutrients, wastes, & other particles are filtered from the blood

  • Bowman’s Space: space inside Bowman’s Capsule

  • Layers of Glomerulus
    1. Capillary Endothelial layer(lines up with vessel)
    2. Basement membrane: SELECTIVELY PERMEABLE; determines what passes through(proteins, large moleules, and glucose should not get through)
    3. Single-celled epithelial layer, through which filtrate passes

glomerulus

The layers of the glomerulus

1. Capillary Endothelial layer(lines up with vessel)

2. Basement membrane: SELECTIVELY PERMEABLE; determines what passes through(proteins, large moleules, and glucose should not get through)

3. Single-celled epithelial layer, through which filtrate passes

What is the bowmans capsule

• Capsule enclosing the glomerulus

  • Bowman's Space is the space inside the capsule where filtrate collects

Urine

• Clear, yellow - amber in color

• pH 4.6 – 8.0; More acidic to protect against bacteria

• Formed by filtration of blood and reabsorption of H2O, electrolytes & nutrients

What is the rate of filtration of plasma?

glomerular filtration

Glomerular filtration:

• rate of filtration of plasma

• Utilizes same processes as the rest of the body in terms of fluid movement (e.g., colloidal osmotic pressure, capillary. filtration pressure, & capillary permeability)

• Chemical composition of filtrate is like plasma EXCEPT it does not contain proteins and large molecules (because the basement membrane keeps large molecules out)

• Amount of filtrate is directly related to the perfusion pressure of glomerular
  capillaries

• Glomerular Filtration Rate (GFR) = rate of filtrate formed each minute ~125 ml/min

What is the Glomerular Filtration Rate (GFR) ?

rate of filtrate formed each minute ~125 ml/min

What is the goal of regulation of renal blood flow

• maintain perfusion necessary for GFR in order to remove waste products from blood

  • large blood flow in necessary to maintain this

Regulation of renal blood flow

• large blood flow necessary to maintain GFR for removal of waste from blood

• Mechanisms

  • Neural (nervous system) and Humoral (endocrine system) Control Mechanisms

    • VASOCONSTRICTORS
      Sympathetic Nervous System (SNS)
      Angiotensin II
      Antidiuretic Hormone (ADH)
      Endothelin

    • VASODILATORS
      Dopamine
      Nitric oxide
      Prostaglandins

• Autoregulartory mechanisms:

  • Geared at maintaining a constant flow of blood to the kidneys; response to blood prerssure

List the renal vasoconstrictors:

sympathetic nervous system, angiotensin II, antidiuertic hormone (ADH), and endothelins

List the renal vasodilators:

dopamine, nitric oxide, and prostagladins

Autoregulatory mechanisms of regulation of renal blood flow

Geared at maintaining a constant flow of blood to the kidneys; response to blood prerssure

• juxtaglomerulular response

  • senses changes in GFR by monitoring systemic BP by senseing stretch of afferent arteriole

  • monitors NaCl concentrations in tubular filtrates(to determine if its too diluted or too concentrated)

  • Determines how much renin should be releases to maintain BP within ranges to maintain relatively constant GFR

Afferent Arteriole Constriction Effect

Decreases blood flow, GFR, and urine output

Efferent Arteriole Constriction Effect

Increases glomerular pressure and GFR (increased resistance to outflow)

What are the tubular components

• site of reabsorption and/or excretion of substances

• Proximal tubule

• loop of henle

• distal convoluted tubule

• collecting tubules

What is the site of …

o Site of MOST reabsorption & secretion – 65%

o Glucose, amino acids, lactate, H2O soluble vitamins, Na, K, Cl, HCO3

o Highly permeable to H2O: solutes move by osmosis

o Reabsorbs Na & H2O equally

o Secretion of hydrogen ions (H+) and organic acids and bases

proximal tubule

What is being described here?

o Controls the concentration of urine

o ADH hormone exerts its effects at this site

o Reabsorbs more Na+ and Cl- than H2O

o AS ions are reabsorbed, filtrate becomes more dilute as it travels through the ascending loop as more solutes are reabsorbed

loop of henle

What is beind descirbed here?

o Impermeable to H2O
o Active reabsorption of Ca & Mg
o NaCl reabsorption continues ~ 10%
o Regulates ____________________
o H+ ions are secretion / HCO3 (bicarbonate) ions reabsorption

distal and collecting ducts

What is renal clearance?

volume of plasma that is completely cleared each minute of any substances that finds its way into the urine

• Different substances have different clearance rates

  • (for ex: glucose hase clearance rate of 0 becase it shouldnt be in urine)

• Renal clearance is determined by

  • (1) ability of substance to be filtered in the glomerulus (large molecules cannot be filtered through glomerulus, so they have a renal clearance of zero

  • (2) ability of tubules to reabsorb or secrete the substance

Regulation of Na and K elimination

• Regulated by GFR

• Aldosterone: promotes water reabsorption & excretion of potassium

• Atrial Natriuretic Peptide (ANP)
  o Located in atria of heart & released in response to stretch
  o Causes vasodilation of afferent and efferent arterioles
  o Inhibits Na reabsorption
  o Inhibits renin, ADH and aldosterone release

Aldosterone

Hormone secreted by the adrenal gland that makes renal tubules permeable to sodium, increasing sodium/water reabsorption and potassium excretion = more volume

Atrial Natriuretic Peptide (ANP)

Hormone from the cardiac atria that causes

• vasodilation of afferent/efferent arterioles,

• inhibits sodium reabsorption

• inhibits ADH release, resulting in decreased blood volume = less volume

Renal regulation of pH

• Kidneys have key role in regulating pH

• Reabsorbs HCO3- and eliminates Hydrogen (H+)

• Goal is to keep pH between 7.35-7.45

Uric acid elimination

• Product of purine metabolism
• Excess levels of uric acid in the blood can cause gout(hyperuricemia)
• Excess levels of uric acid in the urine can cause stones to form in the urine

Urea elimination:

• End product of protein metabolism

• Kidneys regulate levels of urea in the blood stream [blood urea nitrogen = BUN]

  • normal BUN 8-20 mg/dL [increased levels are seen with
    dehydration]

• Urea is filtered in the glomeruli and reabsorbed in the tubules

• An adult usually generates 25-30 gm/day of urea; quantities vary depending on protein in diet, tissue breakdown, GI bleed
  • Decreased GFR = Increased BUN

What is the normal Blood urea nitrogen (BUN) level

8-20 mg/dL

• Decreased GFR = Increased BUN

Drug elimination:

• All drugs must be metabolized and eliminated
• Drugs are metabolized by the kidney or liver
• Most drugs are eliminated in the urine after being metabolized
• Lipid soluble drugs are easily reabsorbed into the bloodstream
• Goal is to convert lipid soluble drugs to water soluble to eliminate

endocrien function of the kidney:

• RAAS: RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM

• Erythropoietin – regulates production of red blood cells; stimulated by hypoxia

  • Red Blood Cells: Men 4.7-6.1 g/dL; women 4.2-5.4 g/dL

  • Hemoglobin:

    • men: 14-18 g/dL

    • Women: 12-16 g/dL

  • Hematocrit:

    • men: 45-52%

    • women 37-47%

  • Vitamin D

    • kidneys help with the reaborption of vitamin D, which increases calcium reabsoption from the GI tract

Erythropoetin does what?

regulates production of red blood cells; stimulated by hypoxia

Men have how many g/dL hemoglobin

14-18 g/dL

Women have how many g/dL hemoglobin

12-16 g/dL

Men have how much Hematocrit (Hct)

45-52%

Women have how much Hematocrit (Hct)

37-47%

test of renal function, Blood tests

• BUN: 8-20

• Creatininte: 0.6-1.2 mg/dL

• electrolyes

• uric acid

• pH

• RBC’s

• GFR: >125

test of renal function, Urine tests

• Urinalysis (UA)

• creatinine clearance

• Urine specific gravity: 1.010-1.025

• Urine osmolality

• Microalbuminuria: early marker of renal disease

What are the small proteins in urine that are a marker of early renal disease?

microalbuminuria

What are the componenets of urine?

• 95% water

• 5% solutes

• ex: urea, K+, uric acid, NaCl

What is the layer of the glomerulus that is selectively permeable?

basement membrane

all of the following are secreted by the kidneys except?

• antidiuretic hormone (ADH)

• erythropoetin

• renin

antidiueretic hormone (ADH)

Obstructive disorders

• something that physically blocks or obstructs the flow of urine from the kidneys

• can occur at any age and affect any level of GU syste,

• Classifications:

  • Lower tract obstruction = below ureterovesical junction and are bilateral vs Upper tract obstruction = above ureterovesical junction and are usually unilateral

• Damage depends upon: degree (partial vs complete or unilateral vs bilateral) and duration (acute or chronic)

• most obstructions are reversible and require prompt intervention

• bilateral acute obstructions may lead to acute renal failure

• untreated leads to atrophy and renal failure

What is a Lower tract obstruction?

below ureterovesical junction and are bilateral

What is a Upper tract obstruction?

above ureterovesical junction and are usually unilateral

What are causes of obstructive disorders?

• Development defects: usually chronic

• pregnancy

• benign prostatic hypertrophy (BPH)

• tumors

• stones: usually acute

• scar tissue from inflammation or infection

• neurological dysfunction (i.e. spinal cord injury)

Mechanisms of renal damage

• stasis of urine: may lead to infection and/or stone formation

• dilation of renal structures causes destruction and atrophy of renal tissues:

  • Hydronephrosis: urine filled dilation of renal pelvis and calices. From Back pressure of fluid

What is hydronephrosis

urine filled dilation of renal pelvis and calices. From Back pressure of fluid

Clinical manefestations of urinary obstruction

▪ Vary depending upon location, cause, and onset

▪ Pain: #1 reason for seeking care. From distension of bladder, renal capsule, or ureters/urethra.

▪ Have signs & symptoms (s/sx) Urinary Tract Infection (UTI): suspect obstruction with recurrent UTI’s

▪ Unilateral: unaffected kidney can maintain function so may have no manifestations for a long time

▪ Incomplete bilateral obstruction: Impaired ability to concentrate urine; polyuria & nocturia

▪ Complete bilateral obstructions: Oliguria or anuria & renal failure

▪ Hypertension (HTN): more common in unilateral due to increased renin secretion

Unilateral obstruction

unaffected kidney can maintain function so may have no manifestations for a long time

incomplete bilateral obstruction

Impaired ability to concentrate urine; polyuria & nocturia(urinating at night)

complete bilateral obstuction

oliguria(too little urine) and anuria(no urination) and renal failure

Hypertension is more common in what kind of obstruction when renin secretion is increased?

unilateral

Renal calculi (nephrolithiasis)

• most commone cause of upper urinary tract infection

• urinary calculi= urolithiasis

• renal calculi= nephroloithiasis

• composed of substances normally excreted into urine

In order for kidney stones to form ..

• The urinary environment must support the growth of the stone

  • urine is super saturated with stone components that bind together to form a nucleus

  • there is a deficiency of inhibitors for stone formation

• tend to form unilaterally

What are factors that contribute to stone formation?

• Anatomic changes

  • Dietary factors: increased calcium intake

  • Intestinal absorption factors: celciac, lactose intolerant

  • Metabolic / endocrine factors: diabetes

  • Presence of a UTI

Calcium stones:

• (70-80% of all stones)
  • Associated with increased serum calcium levels & hyperparathyroidism(having this steals calcium from our blood)

Magnesium ammonium phosphate stones (Struvite Stones)

• Form only in an alkaline environment
• Presence of bacteria that possess the enzyme “urease

Uric acid stones:

Associated with increased uric acid levels from purine (gout)

Cystine stones:

• Rare – associated with genetic defect
• Seen more so in children
• Resemble struvite stones except without presence of infection

Clinical manefestations of kidney stones

PAIN

• Renal colic: stretching of ureter from stones

  • Acute, intermittent, excruciating pain - flank and upper outer abdomen quadrant

  • Pain may radiate to lower abdomen, bladder, or groin area

  • Skin may be cool & clammy

  • Nausea and vomiting (N/V)

• Non colicky renal pain: from kidney itself

  • Dull, deep ache in flank or back

  • Varies in intensity: mild to severe

  • Pain exaggerated by drinking large amounts of water

Renal colic

• The stretching of ureter from stones

  • Acute, intermittent, excruciating pain - flank and upper outer abdomen quadrant

  • Pain may radiate to lower abdomen, bladder, or groin area

  • Skin may be cool & clammy

  • Nausea and vomiting (N/V)

Noncolicky renal pain:

• from kidney itself

  • Dull, deep ache in flank or back

  • Varies in intensity: mild to severe

  • Pain exaggerated by drinking large amounts of water

Urinary tract infection

▪ Most are caused by E. coli (80%)
▪ Bacteria enters through the urethra most commonly
▪ May also enter via bloodstream (urosepsis)
▪ Bladder & kidneys are sterile and should be free of bacteria

Urinary tract infection (UTI) risk factors:

▪ Most common cause: E. coli
▪ Urinary obstruction or reflux: washout obstructed
▪ Impaired bladder emptying: stasis of urine
▪ Men with prostate disease
▪ Sexually active women
▪ Postmenopausal women: loss of protective estrogen
▪ Older adults
▪ Diabetes
▪ Catheterization (CAUTI): bypasses natural defenses-- Most Common Factor in hospitalizations: = FOLEY CATHETER

What is a CAUTI?

Catheter-Associated Urinary Tract Infection; the Foley catheter is the most common factor in hospital-acquired UTIs

Upper UTI (Pyelonephritis) Manifestations

• systemic involvement

• back pain (unilateral or bilateral)

• chills

• costovertebral tenderness

• dysuria

• fever

• frequency

• General malaise

• headache

• pyuria

• rapid onset

• urgency

Lower urinary tract (cystitis) manefestations

• involves bladder

• more common in women; typically uncomplicated infections

• burning cloudy urine

• dyuria

• foul smelling

• urine

• frequency

• lowed abd pain

• lower back pain

• urgency

• usually no fever in adults

Chronic Pyelonephritis

Associated with recurrent infections/inflammation;

caused by:

• reflux,

• recurrent infection,

• or obstruction;

• may lead to renal scarring/atrophy; may be asymptomatic

Infections in special populations:

• Pregnant women

• Children

• elderly

Pregnant women, urinary tract infection

asymptomatic bacteriuria common
o Dilation of segments of the GU system
o Displacement of bladder

Children, urinary tract infection

Pyelonephritis more common
o Premature infants, immunological disease, GU abnormalities
o More severe symptoms (systemic symptoms): fever is a common sign of UTI in children

Eldery, urinary tract infection

• Prevalent in nursing home population
• Immobile, ↓immune response, indwelling foley catheter, senile vaginitis,
• May have vague symptoms;

• confusion( #1 sign of UTI in older person),

• anorexia(in the way that means they dont want to eat, not anorexia nervosa),

• fever may be absent until
  infection worsens

What is hydronephrosis?

urine filled dilation of renal pelvis

What type of stone presents with a UTI?

struvite

What is colicky pain?

acute, intermittent excruciating

What type of bacteria is responsible for 80% of all UTI’s

E. coli

What manefestation is most commonly evident in the elderly with an infection?

confusion

What is glomerular disease?

• inflammatory response and antibody-antigen complexes cause damage to basement membrane allowing larger substances to cross the capillary wall and enter the urine

▪ Principal of renal failure worldwide

Etiology(causes) of glomerular injury

• immune mechanisms: most common

  • injury from antibodies reacting with glomerular antigens

  • injury from circulating antigen-antibody complexes

• Nonimunne

immune mechanisms of glomeruluar injury

• most common

  • injury from antibodies reacting with glomerular antigens

  • injury from circulating antigen-antibody complexes

Nonimmune glomerular injury

Nonimmune
o Metabolic: diabetes
o Hemodynamic: hypertension
o Toxic: drugs, chemicals

Cellular changes glomerular injury

• proliferative: increase in glomerular or inflammartory cell numbers

• membranous: basement membrane thickening

• slcerotic: increased amount of extracellular material and deposit of collagen fibers

What are the types of glomerular injury

1. Acute NephrItic Syndrome

   1. focus on the unerlined I in nephritic, its underlined because nephritic syndrome often comes after an infection

2. Rapidly Progressive Glomerulonephritis

3. NephrOtic Syndrome

   1. O is underlined for osmosis

4. Glomerular lesions associated with systemic disease

Acute nephritic syndrome

• May be caused by systemic disease but most often occurs after an infection with group A beta-hemolyte streptococci, or certain viruses such as measles, mumps, chicken pox

• May be known as poststreptococcal glomerulonephritis

• Associated with immune complex deposits

• More common in children

• Manifestations usually begin 7-12 days post infection

  • Endothelial cells of the glomerulus proliferate causing glomerular enlargement

  • Inflammatory responses occurs and immune complexes become trapped in the capillary
    basement membrane

  • Capillary membrane swells and permeability increases allowing substances such as
    plasma proteins and RBC to cross

Manefestations of Acute nephritic syndrome

▪ Sudden onset hematuria (gross or microscopic)
▪ Proteinuria
▪ Diminished GFR & oliguria(little urine)
▪ Cola-colored urine from degraded RBC’s
▪ Na & H2O retention: leads to HTN & edema
▪ Hypertension and edema
o Acute Nephritic Syndrome has a good prognosis if recognized early

Rapidly progressive glomerulonephritis

▪ Severe glomerular injury that does not have a specific cause - Idiopathic glomerular injury
▪ May occur from immune disorders such as lupus
▪ Progresses rapidly

Nephrotic syndrome

NOT A SPECIFIC GLOMERULAR DISEASE: a group of clinical manifestations from increased glomerular capillary permeability allowing large protein molecules crossing the membrane into the filtrate

Manefestations of neprotic syndrome

o Massive proteinuria(3.5 g/day)
o Hypoalbuminemia (from loss of proteins in urine)
o Lipiduria & Hyperlipidemia (>300 mg/dL)
o Generalized edema (hallmark sign): Anasarca & Ascites: Sodium and water retention due to decreased colloidal osmotic pressure
o ↑ risk of infection: WBC’s are proteins
o ↓ effectiveness of many medications
o ↑risk of thrombus formation

What is the glomerular lesions associated with systemic disease:

Systemic diseases such as Diabetes Mellitus (DM) and Hypertension (HTN) may lead to glomerular injury and subsequent renal disease. These diseases and their effects on the kidney will be discussed in future lectures.

tubulointerstitial disorders:

Disorders of tubular structures within kidney

• renal tubular acidosis

• pyelonephritis

• drug related nephropathies

renal tubular acidosis

• Defect in the ability to reabsorb HCO3 (bicarbonate) and/or excrete H+

• Results in metabolic acidosis

• May result in hypocalcemia , growth retardation in children, osteomalacia, hyperparathyroidism, & rickets

  • kidneys regulate vitamin D, and vitamin D is important for the absorption of calcium, so we get a lot of bone issues from kidney issues

Drug related nephropathies

▪ Structural or functional changes in the kidneys after exposure to drugs
▪ Kidneys are responsible for drug metabolism/excretion, are highly vascular, & are exposed to
any substance in the blood
▪ Tolerance of drug varies with age, renal status, hydration, BP, urine pH
▪ Elderly & individuals with decreased renal function are more susceptible
▪ Examples: Antibiotic, diuretics, NSAIDS

Renal neoplasm

• Wilm’s tumor

• renal cancer: renal cell carcinoma (80-85% of all renal cancers)

What is Wilm’s tumor

▪ More common in children ages 3-5
▪ Typically a solitary mass that may occur in one or both kidneys
▪ Associated with congenital anomalies
▪ Abdominal mass and hypertension

What is renal cell carcinoma?

(80-85% of all renal cancers)
▪ Men are more commonly affected
▪ Originates in renal cortex
▪ Risk factors: Associated with heavy smoking, obesity, and occupational exposure to toxins

What is one of the number one signs of cancer

unexplained, unintended weight loss

Manefestations of renal cell carcinoma

o Asymptomatic
o Hematuria
o Flank pain
o Flank mass
o Weight loss( number one sign of cancer)