BIOL 204 Flashcards

Urinary System

Functions of the Urinary System

Maintenance of internal environment by:
- Filtering blood to remove toxins, metabolic wastes, excess fluid, and excess ions.
- Helping the body achieve acid/base balance.
Production of renin.
Production of erythropoietin.
Metabolism of vitamin D to its active form.

Organs of the Urinary System

(2) Kidneys: manufacture urine.
(2) Ureters: transport urine from the kidneys to the urinary bladder.
(1) Urinary bladder: stores urine prior to micturition (elimination).
(1) Urethra: carries urine to the surface of the body.

Nephron Anatomy

Nephrons are the functional units of the kidney.
Consist of microscopic epithelial tubes that filter blood and manufacture urine.
Approximately one million nephrons per kidney.

Parts of a Nephron

Glomerulus
Glomerular (Bowman's) capsule
Proximal Convoluted Tubule
Loop of Henle
Distal Convoluted Tubule
Collecting Duct
Glomerulus + Bowman's capsule = renal corpuscle
Collecting Duct collects filtrate from multiple nephrons

Nephron Functional Anatomy Review

Nephrons: functional units of the kidney, epithelial tubes that filter blood and manufacture urine.

Two Classes of Nephrons

Cortical:
- Glomerulus in cortex.
- Peritubular capillaries.
- Short nephron loop.
Juxtamedullary:
- Glomerulus at cortex-medulla junction.
- Vasa recta.
- Long nephron loop.
- Function in concentrating urine.

Nephron Anatomy Review

Renal corpuscle + renal tubule = nephron
Glomerulus is a tuft of capillaries that sits in the glomerular capsule
Glomerulus + capsule = renal corpuscle
Renal tubule is one long continuous tube that empties into the collecting tubule, consisting of:
- PCT (Proximal Convoluted Tubule)
- Nephron loop (Loop of Henle)
- DCT (Distal Convoluted Tubule)

Renal Corpuscle and Juxtaglomerular Apparatus

The juxtaglomerular complex includes:

Macula densa cells of the ascending limb of the nephron loop.
Extraglomerular mesangial cells.
Granular cells of the afferent arteriole.

Urine Formation

Three processes used to make urine:

Glomerular filtration
Tubular reabsorption
Tubular secretion

Glomerular Filtration

Glomerular filtration: materials are filtered from the blood of the glomerulus into the lumen of the glomerular capsule.
Driven by glomerular hydrostatic pressure.

Filtration Membrane

Plasma is filtered from the capillary into the renal tubule through this membrane.
Consists of structures of the renal corpuscle.
Has adaptations to promote filtration:
- Fenestrations (pores) in the glomerular capillary endothelium.
- Basement membrane.
- Podocytes of the visceral layer of the glomerular capsule with filtration slits.

Filtration Membrane Details

The filtration membrane prevents:

Filtration of blood cells (due to fenestrations of the glomerular endothelial cell).
Filtration of larger proteins (due to basal lamina).
Filtration of medium-sized proteins (due to the slit membrane between pedicels).

Filtration Mechanism

Filtrate: fluid that collects in the lumen of the glomerular capsule as a result of filtration.
Filtrate = plasma minus large proteins.

Net Filtration Pressure (NFP)

NFP drives the process of filtration.
NFP depends on three forces:
1. Glomerular Hydrostatic Pressure (GHP or HPg): favors filtration
2. Blood Osmotic Pressure (BOP or OPg): opposes filtration
3. Capsular Hydrostatic Pressure (CHP or HPc): opposes filtration
There is no capsular osmotic pressure.

Formula for Net Filtration Pressure (NFP)

$NFP = [HPg] – [OPg + HPc]$

$NFP = Forces that promote filtration – forces that oppose it$

Example:

$NFP = 55 mmHg – [30 mmHg + 15 mmHg]$

$NFP = 10 mmHg$

Since NFP is a positive number, there is net filtration.

Relationships between NFP and GFR

Net Filtration Pressure (NFP) is the driving force for filtration, usually positive, and initiates urine formation.
Glomerular Filtration Rate (GFR): amount of fluid filtered into the glomerular capsule per unit time.
GFR is influenced by:
- NFP (greater pressure -> increased GFR)
- Total surface area of the filtration membrane (greater surface area -> increased GFR)
- Permeability of the filtration membrane

Regulation of Glomerular Filtration Rate (GFR)

Why regulate GFR?

Protects glomerulus during times of high blood pressure.
Maintains GFR during times of low blood pressure.

How?

Autoregulation
1. Myogenic response
2. Juxtaglomerular feedback mechanism
Extrinsic controls
- Renin-angiotensin-aldosterone mechanism activated by:
  - stretch/mechanoreceptors
  - sympathetic nervous system nerves

Autoregulation – Maintain GFR and Homeostasis

Myogenic Response:
- Increased pressure in afferent arteriole -> stretch-sensitive ion channels open -> arteriolar smooth muscle depolarizes/contracts (leads to vasoconstriction) -> NFP and GFR decrease.

Tubuloglomerular Feedback

Juxtaglomerular Apparatus (or Complex): modified ascending tubule & afferent arteriole having granular, macula densa, and mesangial cells.
Function: help regulate GFR and systemic blood pressure.
Granular Cells (JGC): modified smooth muscle cells of the afferent arteriole, mechanoreceptors that sense BP and respond by secreting renin.
Macula Densa Cells: cells of the ascending limb of the loop of Henle that act as chemoreceptors for filtrate [NaCl].
Extraglomerular Mesangial Cells: pass paracrine hormones from MD to GC; contract and alter glomerular surface area.

Tubuloglomerular Feedback Mechanism

Renal tubule (macula densa) provides feedback to the glomerulus to regulate GFR.
[NaCl] in filtrate (filtrate osmolarity) depends on the GFR.
[NaCl] in filtrate is sensed by the macula densa cells.
Two possibilities:
- GFR is low, the osmolarity, [NaCl], of filtrate is low
- GFR is high, the osmolarity, [NaCl] of filtrate is high

Mechanism - GFR Too Low

If GFR is too low:
- Macula densa cells detect reduced osmolarity and [NaCl].
- Macula densa cells release vasodilators onto the afferent arteriole.
- Increased blood flow into the glomerulus -> NFP and GFR increase.

Mechanism - GFR Too High

If GFR is too high:
- Macula densa cells detect increased [NaCl], osmolarity.
- Macula densa cells release vasoconstrictors onto the afferent arteriole.
- Decreased blood flow into the glomerulus -> NFP and GFR decrease.
- Allows more time to process filtrate by slowing GFR.

Extrinsic Controls – via Nervous & Endocrine Systems: Renin – Angiotensin - Aldosterone Mechanism

Stimuli include:
- Reduced stretch (BP) in the afferent arteriole -> stimulation of renin secretion (granular cells).
- Sympathetic stimulation of renin secretion (granular cells).
- Macula densa cells detect reduced [NaCl] -> stimulate renin secretion.
Goal? Maintain systemic blood pressure
Note: the stimulus is decreased BP; the response is increased BP

Action of Renin-Angiotensin-Aldosterone Mechanism

Granular cells secrete renin -> renin converts angiotensinogen to angiotensin I -> angiotensin I converted to angiotensin II by ACE (angiotensin-converting enzyme).
Effects of angiotensin II:
- Powerful vasoconstrictor.
- Increases aldosterone release.
- Stimulates thirst.

Tubular Reabsorption

Many filtered substances are either not found in urine or are found in smaller concentrations than when they were first filtered.
These substances are reabsorbed into the peritubular capillaries as the filtrate moves through the rest of the renal tubule.

Tubular Reabsorption Details

In selective reabsorption, sodium, amino acids, and glucose are reabsorbed from the filtrate back into the blood capillary.
Most reabsorption takes place in the PCT (Proximal Convoluted Tubule).

Reabsorption Mechanisms

Active Transport:
- Primary: fueled by ATP hydrolysis
- Secondary: symport; fueled by $Na^+$ diffusion
Passive Transport:
- Diffusion
- Osmosis

Water Reabsorption

Water reabsorption in the PCT is called Obligatory (Due to aquaporins in PCT).
Water reabsorption in the DCT and CD is called Facultative (No aquaporins in DCT & CD normally).

Tubular Secretion

Transfer of molecules from the peritubular capillaries to the lumen of the renal tubule.
Materials that need to be eliminated but were not filtered (drugs and metabolites bound to plasma proteins).
Reabsorbed waste products (wastes that were passively reabsorbed, i.e., urea and uric acid).
Excess $K^+$ removal ( $K^+$ is reabsorbed in PCT, secretion is under hormone control - aldosterone).
Control blood pH in kidneys (tendency to acidosis):
- Secretion of $H^+$
- Reabsorption of $HCO_3^-$

Countercurrent Multiplier Mechanism

Juxtamedullary nephrons help create urine that is hypertonic to (more concentrated than) the blood.
Osmolarity: The number of particles (ions or intact molecules) per liter of solution.
Osmolality: The number of solute particles per kilogram of solution.
Units are mOsm (“milli-oz-moles”).

Kidney Regulation

Kidney regulates the osmolarity of body fluids in mOsm

Making Concentrated Urine

The kidney makes concentrated urine (hypertonic to plasma) by creating an osmotic gradient in the kidney and using that gradient to influence water reabsorption in the collecting ducts (which are normally impermeable to water).

Osmotic Gradient

The interstitium surrounding the renal tubule must be hypertonic to the filtrate in order for water reabsorption to occur by osmosis.
The kidney creates this gradient using the differing permeability of the limbs of the loop of Henle.

Descending Limb of the Nephron Loop (of Henle)

Water permeable, salt impermeable.
$H_2O$ moves out of the filtrate into the interstitium.
The filtrate loses $H_2O$ but retains salt, thus the filtrate becomes hypertonic to plasma.

Ascending Limb of the Nephron Loop

$Na^+$ and $Cl^-$ are transported into the interstitium in the thick segment.
The thick segment is not $H_2O$ permeable.
The filtrate loses salt but retains $H_2O$ , thus the filtrate becomes hypotonic.

Vasa Recta

Are long, capillary-like vessels that parallel the loops of Henle of juxtamedullary nephrons.
Permeable to both $NaCl$ and $H_2O$ .
Vasa recta preserve osmotic gradient of the medulla.

Antidiuretic Hormone (ADH) and Collecting Duct

$ADH$ causes $CD$ cells to place aquaporins (water channels) across their membranes.
$ADH$ triggers the insertion of aquaporin (water channels) into cells of the collecting duct. This leads to increased water reabsorption and decreased urine volume.

Urea Recycling and Collecting Duct

Urea diffuses out of the terminal portion of the $CD$ into the medulla, then into the ascending limb of the loop of Henle.
Urea permeability is enhanced by $ADH$ in the terminal portion of $CD$ .
Urea recycling contributes to the high osmolarity of the medulla.

Normal urine

Volume: 1-2 liters/day
- abnormally low urine output is oligouria
- abnormally high urine output is polyuria
Color: pale to deep yellow, due to urochrome (a pigment derived from bilirubin)
Odor: slightly aromatic
pH: ranges from 4.5 – 8 (averages 6)
Specific gravity: 1.001 – 1.035

Normal Urine Composition

95% water
5% solutes:
- Nitrogenous wastes: urea, creatinine, uric acid
- Ions: sodium, potassium, phosphate, and sulfate ions

Bladder Filling

	Detrusor (smooth muscle)	Internal Urethral sphincter	External Urethral Sphincter
Type	Parasympathetic (causes contraction)	Sympathetic (causes contraction)	Somatic motor (causes contraction)
During filling	Inhibited	Stimulated	Stimulated
During micturition	Stimulated	Inhibited	Inhibited

Micturition

Micturition is promoted by:
- Increased Parasympathetic activity
- Decreased Sympathetic activity
- Decreased Somatic motor nerve activity

Fluid, Electrolyte and Acid-Base Balance

Body Fluids

Total Body Water:
- Adult males: 57-63% of weight
- Adult females: 50% of weight
- Infants: 73% of weight

Fluid Compartments

Intracellular compartment: contains about 2/3 of the total body water.
Extracellular compartment: contains about 1/3 of the total body water; includes plasma, interstitial fluid, lymph, GI tract secretions, humors of the eye, serous fluid, cerebrospinal fluid, etc.

Functions of $H_2O$ in the Body

Medium for chemical reactions (hydrolysis).
Impacts the concentration of ions and other solutes.
Transports hormones and nutrients.
Transports $O<em>2$ and $CO</em>2$ .
Transports toxins and wastes to the kidney and liver.
Distributes heat around the body.

Solutes

Body fluids contain solutes and water.
Solutes are classified as:
- Electrolytes: solutes that dissociate into ions when placed in water; includes acids, bases, inorganic salts, some proteins.
- Non-electrolyte: do not dissociate into ions when placed in water; includes glucose, amino acids (some), lipids, vitamins.
Electrolyte amount is expressed in a unit called a milliequivalent (mEq), and concentrations are expressed as mEq/L (L=liter).

Milliequivalent Calculation

#mEq/L = \frac{concentration \, of \, the \, ion \, (mg/L)}{atomic \, weight \, of \, the \, ion} \times # \, of \, electrical \, charges \, on \, the \, ion}

Electrolytes in Extracellular Fluid (ECF) vs. Intracellular Fluid (ICF)

ECF: $Na^+$ , $Cl^-$ , $HCO_3^-$ , $Mg^{2+}$
ICF: $K^+$ , $HPO<em>4^-$ , Protein $-,$ SO4^{2-}

Regulation of Body Water

Average daily water gain and water loss in adults:
- Intake:
  - Drink: 1500 ml
  - Food: 750 ml
  - Metabolic: 250 ml
  - Total: 2500 ml
- Output:
  - Insensible water loss (skin, lungs): 700 ml
  - Sweat: 200 ml
  - Feces: 100 ml
  - Urine: 1500 ml
  - Total: 2500 ml

Water Intake

Water intake is regulated by the thirst mechanism
- Plasma osmolality and plasma volume are key factors.

Electrolytes

Na^+ (Sodium):
- Location: most abundant in ECF
- Function(s):
  - Exerts significant osmotic pressure in ECF
  - Needed for normal neuromuscular function
  - Renal acid-base mechanisms are coupled to Na^+ transport
  - Primary/secondary active transport of molecules in the nephron and digestive tract, etc.
- Regulation: aldosterone promotes Na^+ $reabsorption at$ DCT $;$ Na^+ $concentration usually stable since$ H_2O dilutes it.

Potassium

K^+ (Potassium):
- Location: most abundant ion in the ICF
- Function(s):
  - Needed for normal neuromuscular function
  - Needed for protein synthesis
  - Has an impact on acid-base balance
- Regulation:
  - Aldosterone promotes K^+ secretion (blood to filtrate/urine)
  - pH-driven shifts in K^+ $balance (with acidosis, excess$ H^+ $enters cells and$ K^+ $leaves cells; with alkalosis,$ H^+ $leaves cells and$ K^+ enters cells)
  - Acidosis: H+ increases, K+ increases
  - Alkalosis: H+ decreases, K+ decreases

Calcium

Ca^{2+} (Calcium):
- About 99% of Ca^{2+} is found in the skeleton
- Location: ECF
- Function(s):
  - Provides strength to the skeleton
  - Used for blood clotting, neurotransmitter release & other cellular secretion
  - Important 2nd messenger, muscle contraction
- Regulation: parathyroid hormone causes reabsorption at DCT (and absorption in the small intestine) -> elevates plasma Ca^{+2}

Magnesium

Mg^{2+} (Magnesium):
- Location: ICF
- Function(s):
  - Activates coenzymes in cells
  - Used for carbohydrate and protein metabolism
  - Needed for neural and muscular function
- Regulation: PTH inhibits renal reabsorption. So. . .when [Ca^{2+}] $is low in blood, this decreases$ [Mg^{2+}] in blood

Chloride

Cl^- (Chloride):
- Location: ECF
- Function(s):
  - Activates enzymes in secretions (such as pepsinogen in the stomach)
  - Assists in maintaining osmotic pressure
- Regulation: aldosterone usually promotes Cl^- retention unless there is a state of acidosis

Acid Base Balance

Acidity of a solution is dependent on the concentration of free H^+ ions in a solution.
Acidity or alkalinity is measured on a pH scale.

pH = -log[H^+]

The pH scale extends from 0-14, where 7 is neutral.

Sources of Hydrogen Ions (H^+)

H^+ is added to body fluids from the following sources:
- CO_2 production during aerobic respiration.
- Amino acid, glucose metabolism.
- Production of metabolic acids, such as lactic acid.
- Ingested food.

pH Regulation

pH regulation in the body is important because:
- Enzymes, membrane channels, receptors, and other proteins are very sensitive to pH.
- pH changes can change 3D shape and affect function and possibly denature proteins and can destroy their function.

Acidosis vs. Alkalosis

	Acidosis	Alkalosis
Plasma pH	less than 7.35	greater than 7.45
Neurons Excitable	Less excitable	More excitable
CNS	CNS depression	CNS hyperexcitability
Symptoms	Confusion, disorientation, coma	Numbness/tingling, muscle twitches, and tetanus may result
Death	Depression of respiratory neurons	Tetany of respiratory muscles

pH Regulation Mechanisms

Three mechanisms for pH regulation in the body:

Buffer Systems:
- Buffers function to prevent rapid, drastic changes in the pH of body fluids.
- Most of the buffer systems of the body are composed of a weak acid and an anion of that weak acid (the weak base).
- Principle buffer systems of the body are:
  - Proteins – important in ICF and in plasma
  - Phosphate buffer system – important in ICF and in nephron filtrate
  - Bicarbonate buffer system (main ECF $buffer, but also in$ ICF)
Ventilation in Lungs and Acid/Base Status
Renal Function and Acid Base Balance

Buffer Systems

Protein Buffer Systems:
- The most abundant buffer system of both ICF $and$ ECF
- Takes up excess H^+ $preventing acid accumulation and Donates$ H^+ to prevent excessive base accumulation.
Phosphate Buffer System:
- Important in the ICF and in nephron
- Monohydrogen phosphate buffers acid: H^+ + HPO4^- \rightleftharpoons H2PO_4
- Dihydrogen phosphate buffers base: OH^- + H2PO4^- \rightleftharpoons H2O + HPO4^-
Bicarbonate Buffer System:
- H2CO3 buffers base
- Plasma H2CO3 $concentration depends on$ pCO_2
- CO2 + H2O \rightleftharpoons H2CO3

Renal Function and Acid Base Balance

Kidneys alter pH by:
- Secreting or reabsorbing H^+
  - Secrete H^+ -> plasma pH rises
  - Reabsorb H^+ -> plasma pH falls
- Reabsorbing or secreting HCO_3^-
  - Secrete HCO_3^- -> plasma pH falls
  - Reabsorb HCO_3^- -> plasma pH rises

Acid-Base Balance Equations

H2O + CO2 \rightleftharpoons H2CO3 \rightleftharpoons H^+ + HCO_3^-

Key Concepts

Net Production of Acids: As a result of metabolism, the body has a net production of acids from ATP production (CO_2/carbonic acid), or catabolism of protein (amino acids), lipid (fatty acids and ketoacids), carbohydrate (lactic acid).
Kidneys and Lungs: The kidneys along with the lungs maintain the body’s pH by regulating the HCO3^- $/$ CO2 $buffer pair. The lungs exert an immediate effect by controlling$ PCO2 $, the kidneys exert a slower effect by controlling$ HCO3^- $and$ H^+ concentration.
Kidney Homeostasis:The kidneys maintain acid-base homeostasis by reabsorbing filtered bicarbonate and secretion of H^+ and other mechanisms.
Types of Disturbances: There are four types of acid-base disturbances. They are classified by the direction of change in pH (acidosis or alkalosis) and by the underlying physiological problem (ventilation or metabolism).
- Lungs control H2CO3
- Kidneys control HCO_3^-$$
- Hypoventilate: More H2CO3 Plasma pH falls, Acidosis
- Hyperventilate: Less H2CO3 Plasma pH rises, Alkalosis
- Acidify Urine: HCO3- not retained Plasma pH rises, metabolic Alkalosis
- Do not Acidify urine: HCO3- retained Plasma pH falls, metabolic Acidosis