Renal/ Urinary system

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How much of our bodies are water

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1

How much of our bodies are water

60% male

55% female

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Extracellular fluid

1/3

  • 1/5 of ECF is plasma

  • 4/5 of ECF is Interstitial fluid

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Intracellular fluid

2/3

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Maintaining balance

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

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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

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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

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Major organs of the urinary system

  • kidneys (2)

  • Ureters (2)

  • Urinary bladder

  • Urethra

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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

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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

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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

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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

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pathway of urine

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

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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

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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

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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

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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

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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

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Types of nephrons

  • cortical nephron

    • 85%, lies mainly in cortex

  • Juxtamedullary nephrons

    • Extend deep into medulla

    • Important for the formation of concentrated urine

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Function of the nephron

  • function: selectively filter blood

  • Return to blood anything to be kept

  • Carry waste away for storage and expulsion

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Each nephron is comprised of:

  • A glomerular capsule

  • Renal tubules

  • A collecting duct

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Each nephron is associated with:

  • A glomerulus

  • Peritubular capillaries

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Glomerular capillaries

  • specialised for filtration

  • Thin walled single layer of fenestrated endothelial cells

  • Fed and drained by arterioles

  • Blood pressure here is tightly regulated

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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

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The renal corpuscle

  • Glomerulus enclosed by the Glomerular capsule

  • Where capillary and nephron meet

  • Site of filtration barrier

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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

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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

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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

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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

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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

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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

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Distal convoluted tubule (DCT)

  • fine tuning

  • Cuboidal epithelium, but thinner than PCT

  • Structure

    • Few microvilli = no brush border

    • Fewer mitochondria

    • Reabsorption influenced by aldosterone

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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

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transitional epithelium

  • stratified rounded cells

  • Flatten when stretched

  • for protection

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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

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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

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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

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Trigone

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

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Empty bladder

  • Pyramidal

  • Lies within the pelvis

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As bladder fills

  • Become more spherical

  • Expands superiorly into abdominal cavity

  • Can be palpated above pubic symphysis

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Location of bladder

  • male

    • Anterior to rectum

    • superior to prostate gland (wraps around urethra)

  • Female

    • Anterior to vagina and uterus

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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

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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

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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

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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

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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

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Why do we need kidneys

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

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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

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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

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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

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Metabolic: Gluconeogenesis

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

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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

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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

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What if you suffer from kidney failure

hyperkalemia (death)

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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

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Body water balance

  • Total body water remains relatively constant

  • Intake and loss of water must balance

  • Urine output is adjusted to maintain balance

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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

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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

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Hyposmotic

  • increase in water (hyper-hydration)

    • less solute molecules per litre

    • decrease in ECF/Plasma osmolarity

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Hyperosmotic

  • Decrease in water (dehydration)

    • More solute molecules per litre

    • increase in ECF/plasma osmolarity

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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

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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

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basic functions of the nephron

  • Filtration

  • Secretion

  • Reabsorption

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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

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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

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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

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Glomerulus

  • Filtration of plasma

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Proximal tubule

  • secretion of metabolites, medications and toxins

  • Bulk reabsorption of ions, water and nutrients

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Nephron loop bulk reabsorption

  • bulk reabsorption of ions and water

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Distal tubule and collecting duct

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

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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

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Sodium

  • freely filtered

  • Not secreted

  • Almost fully reabsorbed: in most parts of the nephron

  • small amounts excreted in urine

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Glucose

  • freely filtered

  • Not secreted

  • fully reabsorbed: in the proximal tubule

  • None excreted in urine

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Medications and toxins

  • freely filtered

  • entirely secreted

  • Not reabsorbed

  • All in blood is excreted in urine

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Creatinine and inulin

  • freely filtered

  • Not secreted

  • Not reabsorbed

  • All filtered is excreted in urine

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What determines glomerular filtration

  • filtration barrier

  • Renal blood flow

  • Driving forces

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Glomerular filtration : filtration barrier

  • small substances are freely filtered

  • Large substances are NOT filtered

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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

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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

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Glomerular hydrostatic pressure (GHP)

= blood pressure (+50mmHg)

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Blood colloid osmotic pressure (BCOP)

= albumin (-25mmHg)

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Capsular hydrostatic pressure (CsHP)

=pressure of filtration already present (-15mmHg)

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Capsular colloid osmotic pressure (CsCOP)

= no protein in capsular space (+0mmHg)

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Net filtration pressure

GHP - BCOP - CsHP + CsCOP

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renal blood flow

Renal plasma flow

  • 55% of blood is plasma

  • 625mL of plasma/min

  • 45% of blood is cells

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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

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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

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Renal filtered load

  • amount of a particular substance filtered per unit of time

  • GFR x solute plasma conc

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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

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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

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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

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Inulin

  • polysaccharide, not metabolised by the body

  • not found in body, must be injected

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Creatinine

  • waste product produced by muscles

  • Already in the body, so most commonly used clinically

  • Not reabsorbed or secreted

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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

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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

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bulk obligatory water reabsorption

  • accounts for 92% of total water reabsorption

  • not regulated -automatic

  • leaky epithelia

  • trans-and paracellular water reabsorption

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Regulated facultative water reabsorption

  • accounts for 2-8% of total water reabsorption

  • regulated by anti-diuretic hormone (ADH)

  • tight epithelia

  • Only transcellular reabsorption

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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

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Bulk sodium reabsorption

  • accounts for 92% of total sodium reabsorption

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Regulated sodium reabsorption

  • accounts for 7-8% of total sodium reabsorption

  • regulated by aldosterone

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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

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