Renal/ Urinary system

How much of our bodies are water

60% male

55% female

Extracellular fluid

1/3

• 1/5 of ECF is plasma

• 4/5 of ECF is Interstitial fluid

Intracellular fluid

2/3

Maintaining balance

Filtering out blood and expelling excess water, salts, wastes from metabolism and toxins and drugs

The make up of urine

• waste products excreted to maintain balance within the body

• Normal urine contains: water, salts, urea, metabolites, hormones, small proteins

• pH is not tightly regulated (4.6 to 8) influenced by what is excreted

• Useful diagnostic tool for disease states

• Abnormal urine: Large proteins, RBC, Glucose

The urinary system needs

• Delivery system for blood

• Selective filtration system

• Filtrate recovery mechanism

• System to return recovered, filtered fluid to body

• System to remove filtrate from body

• protection

• Ability to communicate with relevant parts of the body

• Adaptable to meet the body’s changing needs

Major organs of the urinary system

• kidneys (2)

• Ureters (2)

• Urinary bladder

• Urethra

The kidney structure allows for

• Blood to be brought into close proximity with the nephron, for filtering

• Blood that has been filtered to leave the kidney

• A pathway for urine to be removed from the kidney, stored and the excreted

• Protection

Location of the Kidneys

• T12 vertebra past 11th and 12th ribs ending at the L3 vertebra

• Convex side faces laterally

• Medial surface has a concave notch called the hilum (renal blood vessels, lymphatic nerves and the ureter)

• Retroperitoneal : located on posterior abdominal wall, covered on anterior side by peritoneum

• Surrounded, supported and protected by fat

Gross structure of the kidney

• Three regions: cortex, medulla and pelvis

• Fibrous capsule

• Inner medulla

  • divided into pyramids

  • each medullary pyramid ends in a papilla

• Outer cortex

  • Continuous layer

  • renal columns

• cortex and medulla

  • Multiple functional lobes

  • 5-11 lobes per kidney

• urine drains from each papilla and collects in a calyx

• Calyces join to form renal pelvis

• Pelvis narrows as it exits the hilum to become the ureter

kidney lobe

• One medullary pyramid

• all cortex that surrounds it (including renal columns, not shown here)

• Made up largely of nephrons -tiny tubes that filter from blood and create urine

pathway of urine

Papilla → minor calyx → major calyx → renal pelvis → ureter

Blood supply to the kidney

• urine is produced by filtering waste from the blood into the nephron

• Filtration occurs in the cortex of the kidney

• Renal artery arises from the abdominal aorta

• Branching arteries get smaller and smaller until they reach the cortex

• Blood is filtered

• veins return filtered blood from the cortex to the renal vein, then to the IVC

What happens to blood in the cortex?

• the afferent arteriole delivers blood from the arteries to the glomerulus

• The glomerulus is made of glomerular capillaries and is where filtration occurs

• The efferent arteriole carries blood from the glomerulus to the peritubular capillaries

• The peritubular capillaries carry blood to the veins

Flow of blood through the kidneys

• blood supply into the cortex to be filtered: Abdominal aorta

  • renal artery

  • Series of arteries

  • afferent arteriole

  • glomerular capillary

• Blood supply away from the cortex after being filtered: Glomerular capillary

  • efferent arteriole

  • Peritubular capillaries

  • series of veins

  • renal vein

  • Inferior vena cava

Nerve supply

• innervation is from a network of autonomic nerves and ganglia called the renal plexus

• Sympathetic nerves act to adjust diameter of renal arterioles and thus regulate blood flow

what is a nephron

• Microscopic functional unit of the kidney

• Bulk of kidney made up of nephrons

• Filters blood

• selectively reabsorbs or secretes

• produces urine

• approx 1 million per kidney

• responsible for urine formation

Types of nephrons

• cortical nephron

  • 85%, lies mainly in cortex

• Juxtamedullary nephrons

  • Extend deep into medulla

  • Important for the formation of concentrated urine

Function of the nephron

• function: selectively filter blood

• Return to blood anything to be kept

• Carry waste away for storage and expulsion

Each nephron is comprised of:

• A glomerular capsule

• Renal tubules

• A collecting duct

Each nephron is associated with:

• A glomerulus

• Peritubular capillaries

Glomerular capillaries

• specialised for filtration

• Thin walled single layer of fenestrated endothelial cells

• Fed and drained by arterioles

• Blood pressure here is tightly regulated

peritubular capillaries

• Specialised for absorption

• Wrap around renal tubules

• Receives filtered blood from glomerulus via efferent arterioles

• Receives reabsorbed filtrate from nephron

• Some non-filtered solutes that need to be excreted can pass from here into nephron

• vasa recta

  • Extensions that follow nephron loops deep into the medulla

  • Only found with juxtamedullary nephrons

The renal corpuscle

• Glomerulus enclosed by the Glomerular capsule

• Where capillary and nephron meet

• Site of filtration barrier

Glomerular capsule

• First part of nephron

• AKA bowmans capsule

• Two layers

  • Outer parietal layer of simple squamous cells

  • Inner visceral layer of podocytes

• Between the two layers is the capsular space which receives filtrate

Podocytes

• Surround the glomerular capillaries

• Very branched, very specialised epithelium

• Branches form intertwining foot processes called pedicels

• Filtration slits form between pedicels

• Filtered blood goes through these slots and passes into capsular space

Filtration barrier

• AKA: Blood-urine barrier/glomerular capsular membrane

• Lie between blood and capsular space

• Allows free passage of water and small molecules

• Restricts passage of most proteins

• RBCs are not filtered into nephron

• Three layers

  • Fenestrated endothelium of glomerular capillary

  • Fused basement membrane

  • Filtration slits between the pedicels of the podocytes

What happens after filtration

• Urine is waste fluid and solutes filtered from the blood

• Not everything that is filtered is excreted

• Some filtrate is reabsorbed

• And some of what wasn’t filtered is secreted into the nephron

• So urine = filtered - reabsorbed + secreted

Proximal convoluted tubule (PCT)

• bulk reabsorption

• surrounded by peritubular capillaries

• Structure:

  • cuboidal epithelial cells

  • Dense microvilli on luminal membrane

  • Highly folded basolateral membrane

  • Many mitochondria for active transport

  • Leaky epithelium

nephron loop

• AKA loop of henle

• Loops down into the medulla - length is important in production of dilute/concentrated urine

• surrounded by vasa recta (Juxtamedullary nephrons only)

• Structure:

  • Thick descending limb - similar to PCT structure

  • Thin descending limb - simple squamous epithelium

  • Thin ascending limb - simple squamous epithelium

  • Thick ascending limb - similar to DCT structure

• Different permeabilities to water and sodium

Distal convoluted tubule (DCT)

• fine tuning

• Cuboidal epithelium, but thinner than PCT

• Structure

  • Few microvilli = no brush border

  • Fewer mitochondria

  • Reabsorption influenced by aldosterone

Collecting duct

• Fine tuning

• Filtrate from several DCTs drains into one collecting duct, which empty at papilla

• Structure

  • wall of simple cuboidal epithelium

  • Principal cells - reabsorption

  • Intercalated cells - Acid/base balance

• reabsorption influenced by aldosterone and ADH

transitional epithelium

• stratified rounded cells

• Flatten when stretched

• for protection

ureters

• Arise from each renal pelvis at each hilum

• Slender tubes that carry urine from kidneys to bladder

• Descend retroperitoneally through abdomen vertically from hila

• peristaltic waves move urine to bladder

• Run obliquely through the wall of bladder at its posterolateral corners

  • acts as a sphincter/ valve: compressed by increased bladder pressure to prevent backflow

• Carry urine from kidney to bladder

Ureter histology

• Three layers

  1. Transitional epithelium

  2. Muscularis (inner longitudinal, outer circular)

  3. Adventitia - outer covering of fibrous connective tissue

• Folded protective protein plaques on inner surface

Urinary bladder

• Collapsible muscular sac

• Stores and expels urine

• When empty the bladder collapses along folds

• when full, the bladder expands without great increase in pressure (~500ml)

• bladder wall- contains muscle for expulsion of urine

Trigone

Triangular region between 2 openings of entry of ureters and 1 opening for urethra

Empty bladder

• Pyramidal

• Lies within the pelvis

As bladder fills

• Become more spherical

• Expands superiorly into abdominal cavity

• Can be palpated above pubic symphysis

Location of bladder

• male

  • Anterior to rectum

  • superior to prostate gland (wraps around urethra)

• Female

  • Anterior to vagina and uterus

Urinary bladder wall

• folded into rugae for expansion

• Muscosa of transitional epithelium

• thick smooth muscle layer called detrusor

  • Longitudinal, circular and oblique fibres

  • Contractions to expel urine from bladder into urethra during urination

urethra

• Thin walled muscular tube

• Drains urine from the bladder out of the body

• Epithelium changes:

  • Transitional near bladder

  • columnar

  • stratified squamous near external opening

• Mucus glands to protect epithelium from urine

Significant differences between males and females urethras

• female:

  • Shorter (~5cm)

  • separate from reproductive system

• male

  • Longer (~25cm)

  • Part of reproductive system

  • initial section surrounded by prostate gland (produces seminal fluid)

  • 3 sections: prostatic, membranous, spongy/penile

urethral sphincter

• internal urethral/Urinary sphincter

  • Junction of bladder and urethra

  • Detrusor muscle

  • Involuntary control

• External urethral/urinary sphincter

  • Located where urethra passes through the urogenital diaphragm

  • Skeletal muscle

  • Voluntary control

Urination

• Bladder fills with urine and expands

• AP from stretch receptors to brain

• Urgency increases as signals increase

• Internal sphincter relaxes

• Conscious relaxation of external sphincter

Why do we need kidneys

To control what is in out blood and how much blood we have

Kidney removal and regulation

• remove waste products from metabolism and breaking down old cell parts

• Remove drugs/medications and toxins

• Balance water ions and pH - by controlling water and sodium the kidneys control the osmolarity and volume of body water

Major functions of the kidney

• endocrine functions

  • Erythropoietin

  • Activation of vitamin D into calcitriol

  • renin secretion

• Metabolic functions

  • Gluconeogenesis

• pH regulation

• Water homeostasis

  • ECF osmolarity, blood pressure

• salt/ion homeostasis

  • Na+, K+, blood pressure

• Reabsorption of nutrients

  • Amino acids, glucose

• Excretion of medications, toxins and metabolites

  • Aspirin, lignocaine

  • Urea, Uric acid

Erythropoietin (EPO) in kidney

• low blood oxygen levels are detected by the kidneys

• The kidney release EPO

• EPO stimulates the bone marrow to produce more red blood cells

Chronic kidney/ renal failure

• the kidney cannot make enough EPO

• reduced red blood cell production

• Anaemia: low blood oxygen levels

Metabolic: Gluconeogenesis

• during fasting, or when our body is under stress: the kidneys make glucose (from lactate)

pH regulation of the kidneys

• pH is a measure of how acidic or alkaline a solution is:

  • pH=-long[H+]

  • pH is the inverse of H+ ion concentration

  • The more H+ ions there are the lower the pH =more acidic (acidosis)

  • The fewer H+ ions there are the higher the pH = more basic/alkaline (Alkalosis)

  • Normal blood pH range = 7.35- 7.45

• two main sources of acid in the body:

  • Acids coming from metabolism, food and drink (different sources of H+ → non-volatile acids)

  • carbon dioxide from metabolism

• The pH of the blood is controlled by:

  • Lungs: exhalation of CO2

  • Kidneys: reabsorption and secretion of bicarbonate and hydrogen ions

Salt/ion homeostasis of the kidney

• potassium conc is vital for many processes

• All cells

  • the resting membrane potential is based on k+ gradient (inside/outside) of cells

• Neurons and cardiomyocytes

  • action potentials, rhythm generation in pacemaker cells, contractility, signalling

• Kidneys secrete K+, to maintain potassium balance

What if you suffer from kidney failure

hyperkalemia (death)

Excretion of medications

• lidocaine is commonly used local anaesthetic

  • excreted by the kidneys after metabolism in the liver due to its fat soluble (lipophilic) nature

• Aspirin is a common pain killer

  • excreted directly by the kidneys due to its high water solubility (hydrophilic)

• Medications are filtered and secreted by the kidneys to be excreted from the body in the urine

Body water balance

• Total body water remains relatively constant

• Intake and loss of water must balance

• Urine output is adjusted to maintain balance

Volume of fluid in the body water compartments can change due to:

• how much water there is in the body

• the osmolarity of the body water compartments (water moves to where the osmolarity is highest)

• Increase in plasma: increase in BP

• Decrease in plasma: decrease in BP

• Increase in ICF: swelling of cells

• Decrease in ICF: Shrinking of cells

Osmolarity

• The total number of solute molecules in a solution

• ECF fluid 275-300mosmol/L

• ICF fluid 275-300mosmol/L

• A change in the amount of water in the ECF changes the osmolarity

Hyposmotic

• increase in water (hyper-hydration)

  • less solute molecules per litre

  • decrease in ECF/Plasma osmolarity

Hyperosmotic

• Decrease in water (dehydration)

  • More solute molecules per litre

  • increase in ECF/plasma osmolarity

Loss or gain of water

• water is lost or gained in the ECF

• osmolarity balances ECF and ICF

• Gain water or loss of water in both ECF and ICF

Loss or gain of isosmotic fluid

• loss and gain only in ECF

• osmolarity remains the same (ions are lost and gained as well as water)

• Only ECF is effected and no NET water movement

basic functions of the nephron

• Filtration

• Secretion

• Reabsorption

Filtration of the nephron

• occurs in the renal corpuscle/glomerulus

• movement of plasma from the glomerular capillaries into the glomerular capsule

• Most substances in plasma are freely-filtered

  • exception: large proteins and substances bound to proteins

  • Water and solutes are filtered at a constant rate at the renal corpuscle

• Creates a plasma-like filtrate of the blood

• Not very selective at the glomerulus

Secretion of the nephron

• movement of solutes from the peritubular capillaries into the tubular fluid

• removes additional substances from the blood by secreting them into the tubular fluid so they are excreted in the urine (metabolites, medications and toxins)

Proximal tubule:

• secretion of metabolites medications and toxins

reabsorption in the nephron

• Movement of solutes from the tubular fluid into the peritubular capillaries

• returns useful substances to the blood so they are NOT excreted in the urine

• Proximal tubule

  • Bulk reabsorption of ions, water and nutrients

• Nephron loop:

  • Bulk reabsorption of ions, water

• Distal tubule and collecting duct

  • Fine-tuning reabsorption of ions and water

Glomerulus

• Filtration of plasma

Proximal tubule

• secretion of metabolites, medications and toxins

• Bulk reabsorption of ions, water and nutrients

Nephron loop bulk reabsorption

• bulk reabsorption of ions and water

Distal tubule and collecting duct

• fine-tuning/regulated (by hormones) reabsorption of ions and water

Functions of each part of the nephron is determined by

• amount filtered + amount secreted - amount re-absorbed = the amount of a substance excreted in the urine

Sodium

• freely filtered

• Not secreted

• Almost fully reabsorbed: in most parts of the nephron

• small amounts excreted in urine

Glucose

• freely filtered

• Not secreted

• fully reabsorbed: in the proximal tubule

• None excreted in urine

Medications and toxins

• freely filtered

• entirely secreted

• Not reabsorbed

• All in blood is excreted in urine

Creatinine and inulin

• freely filtered

• Not secreted

• Not reabsorbed

• All filtered is excreted in urine

What determines glomerular filtration

• filtration barrier

• Renal blood flow

• Driving forces

Glomerular filtration : filtration barrier

• small substances are freely filtered

• Large substances are NOT filtered

Glomerular filtration : renal blood flow

• renal blood flow = ~1/5th of Co per min

• RBF ~1100-1200mL blood/min

• High flow for filtration, rather than metabolism

Glomerular filtration: driving forces

• there are 2 types of forces

• Hydrostatic pressures

  • Pressure due to the volume of fluid

  • Pushes fluid away

• Colloid osmotic pressures

  • Osmotic pressure due to protein

  • Pulls fluid towards

• positive pressures favour filtration

• Negative pressures oppose filtration

Glomerular hydrostatic pressure (GHP)

= blood pressure (+50mmHg)

Blood colloid osmotic pressure (BCOP)

= albumin (-25mmHg)

Capsular hydrostatic pressure (CsHP)

=pressure of filtration already present (-15mmHg)

Capsular colloid osmotic pressure (CsCOP)

= no protein in capsular space (+0mmHg)

Net filtration pressure

GHP - BCOP - CsHP + CsCOP

renal blood flow

Renal plasma flow

• 55% of blood is plasma

• 625mL of plasma/min

• 45% of blood is cells

Filtration fraction

Glomerular filtration rate/ Renal plasma flow

• ~20% of the RPF is filtered

• ~80% remains in the glomerular capillaries → the efferent arteriole → peritubular capillaries

Glomerular filtration

• plasma filtered by the kidney per unit time

  • 180L/day

  • 125mL/minute

• but produces only 1.5L of urine per day

  • Tightly regulated

  • variation from person to person

  • Declines slowly from age 30

• The amount of plasma filtered per unit time by the kidneys is the glomerular filtration rate

Renal filtered load

• amount of a particular substance filtered per unit of time

• GFR x solute plasma conc

Renal clearance

• clearance is the volume of plasma that is cleared of a substance by the kidneys per unit time

• clearance can be used to

  • Quantify how a substance is handled by the kidneys

  • Estimate glomerular filtration rate

Clearance (Cx) =

(Ux x V)/Px

Ux = conc of X in urine

V= volume of urine produced per unit time

Px = conc of X in plasma

To use the measure GFR a substance must:

• Be freely filtered

• Not be reabsorbed from the tubule

• Not be secreted into the tubule

• Only inulin and creatinine meet these requirements

Inulin

• polysaccharide, not metabolised by the body

• not found in body, must be injected

Creatinine

• waste product produced by muscles

• Already in the body, so most commonly used clinically

• Not reabsorbed or secreted

Plasma creatinine conc is an indicator of kidney function:

• if both kidneys are working plasma creatine is low

• even if only one kidney is still working, plasma creatinine is fairly normal

• When GFR <25mL/min plasma creatinine conc increases as the kidneys ability to clear waste products from the blood is reduced

Water reabsorption in the nephron

• There are three important places where water is reabsorbed in the nephron:

  • Proximal convoluted tubule

    • 67% of filtered load reabsorbed

  • Descending limb of the nephron loop:

    • 25% of filtered load reabsorbed

  • Collecting duct

    • 2-8% of filtered load reabsorbed

• Excretion - <1-6% of filtered load is excreted

bulk obligatory water reabsorption

• accounts for 92% of total water reabsorption

• not regulated -automatic

• leaky epithelia

• trans-and paracellular water reabsorption

Regulated facultative water reabsorption

• accounts for 2-8% of total water reabsorption

• regulated by anti-diuretic hormone (ADH)

• tight epithelia

• Only transcellular reabsorption

Sodium Reabsorption in the nephron

• there are four important places where sodium is reabsorbed in the nephron:

  • Proximal convoluted tubule

    • 67% of filtered load reabsorbed

  • Ascending limb of the nephron loop:

    • 25% of filtered load reabsorbed

  • Distal convoluted tubule

    • 5% of filtered load reabsorbed

  • collecting duct

    • 2-3% of filtered load reabsorbed

• excretion <1% of filtered load is excreted

Bulk sodium reabsorption

• accounts for 92% of total sodium reabsorption

Regulated sodium reabsorption

• accounts for 7-8% of total sodium reabsorption

• regulated by aldosterone

What drives and regulates body water homeostasis

• Distribution of body water

• Osmolarity/tonicity of solution

• Changes in blood osmolarity

• Reabsorption of water and sodium in the nephron

• Effects of osmotic changes on the kidney

• Effects of volume changes on the kidney