Urinary System Flashcards

Gross Anatomy of the Kidneys

• The kidneys are located in the retroperitoneal space, posterior to the peritoneum.
• They extend from the T12 to L3 vertebrae.
• They are protected posteriorly by the floating ribs.

Connective Tissue Layers Encapsulating the Kidneys

• Renal Fascia:
  • Most superficial layer.
  • Dense connective tissue.
  • Surrounds both kidneys and adrenal glands.
• Perinephric/Perirenal Fat Capsule:
  • Layer of adipose tissue.
• Renal Capsule:
  • Directly covers the outer surface of the kidney.

Internal Kidney Anatomy

• Renal Cortex: Outer regions (granular, reddish-brown).
• Renal Medulla: Inner regions (composed of renal pyramids with a striped appearance).
• Renal Columns: Separate renal pyramids.
• Major and Minor Calyces: Collect urine from renal lobes (a pyramid and surrounding cortical tissue).

Structure and Function of the Ureters

• Carry urine from the kidneys to the bladder.
• Capable of peristalsis.
• Connect to the bladder at an angle that prevents backflow of urine.
• Further bladder filling compresses the distal end of the ureter, further preventing backflow.

Microscopic Anatomy of the Ureters

• Deepest Layer (Mucosa):
  • Transitional epithelium.
  • Readily stretches to accommodate distension from urine filling.
• Middle Layer (Muscularis):
  • Senses distension with urine filling and triggers reflexive peristalsis.
• Superficial Layer (Adventitia):
  • Fibrous connective tissue.
  • Anchors the ureter in place.

Common Features of the Bladder

• Trigone: Triangular area at the bottom of the bladder marked by the openings for the paired ureters and the urethra.
• Inner Mucosa: Transitional epithelium that folds into rugae.
• Middle Layer (Detrusor): Contains muscle that contracts to drive urination.
• Thick muscle near the urethra forms the internal urethral sphincter.
• Epithelium transitions to stratified squamous epithelium near the urethra’s opening to the outside.
• Passes through a ring of skeletal muscle on its way out (external urethral sphincter).

Female Urinary System

• Urethra is only 3-5 cm in length and functions only in the transport of urine.

Male Urinary System

• Urethra is longer (20 cm) and functions in the transport of both urine and semen.

Micturition Reflex

• Bladder is continuously being filled.
  • Sympathetic innervation.
  • Smooth muscle contraction in the internal urethral sphincter.
  • Relaxation of detrusor smooth muscle as it stretches.
• Micturition requires 3 things to occur:
  • Conscious decision to relax external sphincter (alpha-motor neuron).
  • Automatically relax the internal sphincter and open the bladder neck (sympathetic).
  • Automatically contract the detrusor smooth muscle (parasympathetic).

Overall Structure of Kidney Vasculature

• Renal artery enters at the hilum.
• Branches into several segmental arteries, which branch into interlobar arteries.
• Interlobar arteries travel through the renal columns and branch into arcuate arteries in the cortex.
• These branch into cortical radiate arteries, then microscopic afferent arterioles.

Overall Structure of Kidney Nephrons

• Nephron: Structural and functional unit of urine formation in the kidney.
• Afferent arterioles drain into the glomerulus.
• Filtration occurs when fluid and solutes are forced from the blood in the glomerulus into the space in the surrounding Bowman’s capsule.
• Blood is drained from the glomerulus by efferent arterioles.

Flow of Fluid Through the Nephron’s Tubules

• Proximal Convoluted Tubule (PCT):
  • Located entirely within the cortex.
  • Simple cuboidal epithelium with microvilli.
• Descending Tube (DT):
  • Descends into the medulla.
  • Alternates between thick and thin segments.
• Loop of Henle (LH):
  • Connects ascending and descending tubes.
• Ascending Tube (AT):
  • Alternates between thick and thin segments.
• Distal Convoluted Tubule (DCT):
  • Simple cuboidal epithelium without microvilli.

Flow of Fluid After Filtration Through the Nephron

• Filtrate from many nephrons.
• Collecting Duct (CD):
  • Principal Cells:
    • Adjust urine in order to maintain the body’s water, Na^+ and K^+ balance.
  • Intercalated Cells:
    • Responsible for acid-base balance.
• Papillary Duct.

Juxtamedullary Nephron

• 15% of nephrons.
• Much longer nephron loop which extends deeper into the medulla.
• Vasa recta are long, straight blood vessels which are associated with the extended loop.

Anatomy of the Juxtaglomerular Apparatus (JGA)

• Occurs when a portion of the DCT comes into contact with the afferent arteriole.
• Macula Densa Cells:
  • In renal tubule.
  • Monitor concentrations of Cl^- and Na^+ in filtrate.
• Granular (a.k.a. Juxtaglomerular) Cells:
  • Respond to changes in blood pressure in the afferent arteriole.

Human Fluid Pools

• Human body composed of three interconnected pools:
  • Intracellular Fluid:
    • Inside cells.
  • Intravascular Fluid:
    • In blood vessels.
  • Interstitial Fluid:
    • Between cells.
  • Extracellular:
    • Interstitial + Intervascular.

Fluid Pool Solute Profiles

• Intracellular Fluid (ICF):
  • Water, electrolytes, small molecules, non-electrolytes, proteins.
  • 20% to 30% protein, pH 7.00.
  • K^+ most common.
• Extracellular Fluid (ECF):
  • Far less protein, electrolytes.
  • pH 7.40.
  • Na^+ most common.

Thirst

• Thirst is a sensation generated by:
  • Exercise, eating salty food, dry mouth.
  • A 1% to 2% increase in osmolarity.
    • Osmolarity – solutes/L, expressed as Osmoles/liter.
    • 0.290 to 0.295 Osm/L.
  • Blood loss.
  • Release of antidiuretic hormone (ADH).
• Thirst is quenched as soon as water contacts osmolarity receptors in our cheeks – this happens to prevent over-consumption of water.

Water Loss

• Kidneys (60%).
• Sweat (8% or more) - depends on external temperature, humidity, and activity level.
• Lungs (28%) - breathing.
• Feces (4%).

Water Loss (mL) at Different Conditions:

Clinical Disorders Related to Water Balance

• Dehydration:
  • Excessive water loss via sweating, diarrhea, vomiting, little water ingestion.
  • Clinical symptoms include:
    • Sticky oral mucosa
    • Dry, flushed skin
    • Reduced urine formation
    • Thirst
    • Weight loss
    • Fever, CNS abnormalities and death
• Hypotonic Hydration (rare):
  • Ingestion of too much water.
  • Decrease in fluid pool osmolarity.
  • CNS dysfunction.
• Hypovolemia:
  • Loss of plasma volume.
  • Loss of water and solutes.
  • Diabetes, burns, wounds, diarrhea, vomiting.
• Hypervolemia:
  • Too much plasma volume.
  • Renal or liver failure.

Fluid Pools are Interconnected

• Fluid constantly moves between pools in response to changes in pressure and osmotic gradients via aquaporin channels expressed in all cells.
• A change in the osmolarity of any pool means that the osmolarity of all pools changes!

Filtration

• The first step of urine formation.

• Layers of the Filtration Barrier:

  1. Capillary Endothelium:

     • Fenestrated; very permeable.
     • Allows passage of anything smaller than a cell.

  2. Basement Membrane:

     • Fused; not as permeable.
     • Blocks all but small proteins.

  3. Podocytes of Glomerular Capsule:

     • Pedicels create filtration slits.
     • Prevents passage of most molecules.

Filtration Pressures

• Filtration is driven by pressure differences.

  • GBHP: Glomerular blood hydrostatic pressure.
    • Blood pressure within the glomerulus.
    • Drives filtration.
  • CHP: Capsular hydrostatic pressure.
    • Hydrostatic pressure inside glomerular capsule.
    • Opposes filtration.
  • BCOP: Blood colloid osmotic pressure.
    • Osmotic pull of proteins not being filtered.
    • Opposes filtration.
  • NFP: Net filtration pressure.

• NFP = GBHP – (CHP + BCOP)

Glomerular Filtration Rate (GFR)

• Glomerular filtration rate = the total volume of filtrate formed by all of the glomeruli of both kidneys each minute.
• The magnitude of NFP is directly proportional to GFR.

Approximating GFR using Renal Clearance

• C = \frac{UV}{P}
  • C = rate of renal clearance, typically in mL/min
  • U = concentration of substance in the urine
  • V = rate of urine formation
  • P = concentration of substance in the blood plasma
• Assumptions for substance to approximate GFR:
  • It must freely pass through the filtration membrane.
  • It must neither be reabsorbed from nor secreted into the filtrate by the renal tubules.

Tubular Reabsorption

• PCT:
  • Na^+ reabsorbed by primary active transport.
  • Glucose, amino acids, proteins, vitamins reabsorbed by secondary active transport.
  • HCO3^-, Ca^{2+}, Mg^{2+}, PO4^{3-}, K^+ also actively reabsorbed.
  • Water and other ions passively reabsorbed by osmosis.
• Ascending and descending loops:
  • Majority of remaining water, Na^+, Cl^- and K^+ is reabsorbed.
  • Opposing permeability: descending loop is permeable to water, ascending loop is permeable to solutes.

Countercurrent Multiplier

• Countercurrent: filtrate is moving in opposite directions in each loop.
• Multiplier: gradient between filtrate and peritubular fluid concentrations increases throughout the system.
• Establishes a medullary osmotic gradient.

Baroreceptors

• LOW PRESSURE sensors:
  • Atrial stretch receptors.
  • Juxtaglomerular apparatus (JGA).
  • Baroreceptors in the CNS, liver, and pulmonary veins
• HIGH PRESSURE sensors:
  • Carotid sinus baroreceptors.
  • Aortic arch baroreceptors.
  • Renal afferent arterioles
• Hemodynamic control – changes in blood volume without changes in osmolarity.

Hormonal Control Points for Plasma Volume

• Kidney: Renin
• Adrenal gland:
  • Angiotensin II
  • Aldosterone

Control Points for Plasma Osmolarity

• Hypothalamic osmoreceptors
  • Thirst
  • Release of ADH
• Kidney
  • Urine formation
  • Solute/water loss

Ion Imbalance

• Hyponatremia:
  • Low plasma Na^+
  • Renal disease, congestive heart failure, Addison’s disease
  • Symptoms are all CNS dysfunction
• Hypernatremia:
  • High plasma Na^+
  • Dehydration, vomiting, diarrhea
  • Symptoms are all CNS dysfunction
• Hypokalemia:
  • Low plasma K^+
  • Vomiting, diarrhea, Cushing’s disease
  • Muscle weakness
• Hyperkalemia:
  • High plasma K^+
  • Renal Failure, Addison’s disease
  • Muscle fatigue, heart abnormalities
• Hypocalcemia:
  • Low plasma Ca^{2+}
  • Muscle stiffness, spasms
  • Hypotension, heart failure, arrhythmia
• Hypercalcemia:
  • High plasma Ca^{2+}
  • Frequent urination, nausea, vomiting
  • Muscle weakness, heart abnormalities

Acid-Base Balance

• Typical blood pH is 7.4 +/- 0.05 due to constant CO_2 production during cellular metabolism
• CO2 + H2O
• Any compound that contributes H^+ is an ACID and any that accepts H^+ is a BASE
• pH represents a balance between CO_2 production and loss (respiration)
• Increased CO_2 drives the reaction to the right, increasing H^+ concentration
• Decreased CO_2 drives the reaction to the left, decreasing H^+ concentration
• Blood pH is tightly regulated in the body, even small changes can be harmful
• ACIDOSIS is a blood pH level below 7.35
• ALKALOSIS is a blood pH level above 7.45

Buffers

• Buffers resist significant changes in pH
• There are four major buffering mechanisms in the body:
  • carbonic acid/bicarbonate: CO2 + H2O
  • phosphate molecules: H2PO4
  • ammonium/ammonia: NH4^+ 3 + H^+
  • amino acids in proteins: RCOOH
• Each of the reactions above are reversible and driven by the concentration of the reactants.

Organs that Impact Acid-Base Balance

• LUNGS: Loss of CO2 (exhalation), represents the loss of protons via: CO2 + H2O 2CO3 3^- and H^+
• Conversion of CO2 to carbonic acid and its rapid conversion to bicarbonate and protons occurs primarily near tissues that need O2
• The local increase in protons triggers the Bohr effect - hemoglobin in RBCs release O_2 to the tissues

Kidneys and pH Regulation

• Operate in the longer term
• In the proximal collecting duct (PCT)
  • Na^+ secretion drives the secretion HCO_3^- and the reabsorption of H^+ in the blood
  • Lowers blood pH
  • Na^+ is reabsorbed into the PCT epithelia in exchange for protons
  • Increases blood pH
• Non-PCT tubular epithelium deaminates glutamate to form a ketoacid + HCO_3^-
• The products of that reaction compensate for acidosis by reabsorbing HCO3^- in the blood and adding phosphate (PO4^{3-}) or ammonia (NH_3) to the fluid in the lumen
• Both accept H^+ preventing it from being reabsorbed by the blood acting as buffers

Intercalated Cells in the Collecting Duct

• Type A intercalated cells:
  • Secrete HCO_3^- which is reabsorbed into the blood, and actively transport H^+ into the lumen
• Type B intercalated cells:
  • Actively secrete H^+ which is reabsorbed by the blood and secrete HCO_3^- into the lumen

Clinical Acid-Base Disorders

• ACIDOSIS: Blood pH < 7.37
  • Respiratory acidosis:
    • Inability to lose CO_2 at the lungs
    • Commonly caused by cardiac failure, opioid overdose
  • Metabolic acidosis:
    • Overproduction of non-volatile organic acids – caused by diabetes, exercise, starvation
    • Kidney damage preventing proton secretion
    • Severe diarrhea causing excessive bicarbonate loss
• ALKALOSIS: Blood pH > 7.43
  • Respiratory alkalosis:
    • Hyperventilation and excessive CO_2 loss at the lungs
    • Can be acute (rare) or chronic (e.g. high altitude sickness)
  • Metabolic alkalosis:
    • Over-secretion of stomach acid or vomiting

Renin-Angiotensin-Aldosterone Pathway

• Renin release from granular cells of kidney in response to low Blood Pressure.
• Angiotensinogen converted to Angiotensin I, then via ACE (Angiotensin-converting enzyme) to Angiotensin II.
• Angiotensin II causes: Thirst, Aldosterone release from adrenal cortex (Na^+ reabsorption in kidneys), ADH release from posterior pituitary (H_2O reabsorption in kidneys), and Vasoconstriction which results in an increased Blood Volume and Peripheral Resistance ultimately raising Blood Pressure.

Polycystic Kidney Disease (PKD)

• WHAT IS IT?
  • Cysts found primarily in the kidney, but can also affect the liver, pancreas, spleen and ovaries
• CAUSES
  • Genetic: autosomal dominant inheritance
• SYMPTOMS
  • High blood pressure, lower back pain, intra-abdominal swelling, blood in urine and frequent bladder/kidney infections.
  • Typically leads to kidney failure.
• CURE
  • Currently none.

Effects of Aging on Kidneys and Urination

• Steady decrease in the number of functional nephrons (approx. 40% lost between the ages of 20 and 70)
• Progressive damage to the filtration membrane and declining renal blood causes a decrease in GFR (approx. 50%)
• Loss of sensitivity of distal renal tubules and collecting ducts to ADH causes excessive loss of Na^+ in urine
• Gradual decrease in bladder size causes more frequent emptying and nocturia
• Loss of muscle tone and control of external urinary sphincter causes urinary incontinence
• Compression of the urethra by an enlarged prostate in males causes urinary retention