Physio: Kidneys

Functions of Kidneys

• Regulates ECF volume and blood pressure

• Regulates Osmolarity of ECF

• Regulates ion concentration of ECF

• Regulates pH of ECF

• Produces hormones

• Excretes waste and foreign substances from plasma

Four ways we excrete water

• Skin: Uses water to thermoregulate (sweat). Sweating gets rid of extra body heat & cools the body

• Lungs: Water is used to humidify the air (in conduction zone)

• Urine: Fine tuning indicator → allows us to determine water intake/output

• Feces: Excretes water and water is used to move fecal material out of the intestines.

  • Constipation = little water

  • Diarrhea = a lot of water

Structure of Urinary system

• Paired kidneys are on either side of vertebral column below diaphragm (size of a fist)

• Urine flows from kidneys → ureters → bladder → urethra

• Walls of bladder are made up of three layers called the detrusor muscles

Renal agenesis

• When a person has only one kidney

• 1/750 people will have this

Internal sphincter

• Part of detrusor muscle

• When your bladder is empty, your muscles become so contracted & this sphincter will relax & twist

• When your bladder is full, the walls of this sphincter will separate and open

External sphincter

• Below the urogenital diaphragm and is made out of skeletal muscle

• Able to relax and contract

• Relaxation will allow urine flow through the urethra

• Contraction will tighten the sphincter, blocking urine from passing

Micturition

Peeing

Trigone

• Important for sending information in to form a reflex arc

• This reflex arc causes contraction and relaxation of the sphincters and bladder walls

• We are able to control this reflex arc, allowing us to control micturition

Nephron

• Functional unit of kidney responsible for forming urine (1 million nephrons/kidney)

• Two types of nephrons

  • Cortical Nephrons are shorter & loop of henle is only halfway of the medulla

  • Juxtamedullary Nephrons are longer

  • They have the same function

• A long tube & has associated blood vessels

Renal Blood Vessels

• Only tissue in the body that has two capillary beds linked in the tissue

• Renal artery → interlobar artery → arcuate artery → interlobular artery → nephron

• Afferent arteriole = Goes into the first capillary bed (glomerulus)

• Efferent arteriole = Goes into second capillary bed (peritubular capillaries)

Bowman’s Glomerular Capsule

• Only function is to filter blood into bowman’s capsule

• Surrounds glomerulus → together forms the renal corpuscle

• This is where plasma will get filtered & turn into filtrate

How much of total blood flow in the body goes into the kidney?

22.8% of total blood flow per minute

Glomerular filtration

• Important for urine production = no filtration, no urine

• Glomerular capillaries & Bowman’s capsule form a filter for blood

• Glomerular capsules are fenestrated → have large pores between its endothelial cells

  • Allows for fluid to flow between them

  • 100-400x more permeable than other capsules

  • Small enough to prevent RBCs, platelets, and WBCs from entering glomerulus

  • Pores are lined with negative charges to keep blood proteins from filtering

• Podocytes cover the inner layer of Bowman’s capsule

  • Have slits that act as “membrane/barrier”

Factors that affect entrance into Bowman’s capsule

• The pores between the endothelial cells of the glomerular capillary

• An acellular basement membrane

• The filtration slits between the podocytes

How much of blood that goes into the kidneys gets filtered?

• 20% of blood that goes into kidneys gets filtered

• 80% of blood will go back into the body via reabsorbption

Glomerular filtration rate (GFR)

• Volume of filtrate produced by both kidney/minute

• Average

  • 115 mL/min for women

  • 125 mL/min for men

• 180 L/day of filtrate produced

• Most filtered water must be reabsorbed or death would ensure from large amounts of water loss through urination

How afferent arteriole affects GFR?

• Major control of GFR is by changing the diameter of the afferent arteriole

• Vasodilation = Increases blood flow into the glomerulus, increased glomerular capillary BP, increased GFR

• Vasoconstriction = decreases blood flow into the glomerulus, decreased glomerular capillary BP, decreased GFR

Sympathetic Effects

• Sympathetic activity (when BP is low or exercise)

  • Constricts afferent arteriole → decrease GFR → decrease urine production/excretion → increase blood flow

• Helps maintain BP and shunts blood to heart and muscles

Glomerular Ultrafiltrate

• Plasma gets into the glomerular/Bowman’s capsule by pressure

• Everything in plasma gets filtered (except large plasma proteins)

  • Glucose, lipids, vitamins will be reabsorbed by kidneys

  • If kidneys detect a foreign substance/doesn’t recognize, it will excrete by urine

Nephron segments

Renal corpuscle → proximal convoluted tubule → Loop of Henle → collecting duct → distal convoluted tubule

Reabsorption of salt & H20

• In proximal convoluted tubule, molecules & H20 from ultrafiltrate start to return back to peritubular capillaries

• About 180 L/day are produced; only 1-2 L of urine excreted every 24 hours

• Urine volume varies according to needs of body

• Obligatory water loss = Minimum of 400 mL/day urine necessary to excrete metabolic wastes

  • If not met, we will start retaining waste in the body

Reabsorption

• Return of filtered molecules

• Kidneys to body

• Occurs primarily in proximal convoluted tubule

How does filtrate in kidneys go back to bloodstream (reabsorption)

• The apical membrane has tons of symporters that are linked to sodium.

• The basolateral membrane will contain the sodium potassium ATPase pumps.

Glucose clearance

Glucose gets into the nephron and ALL of it gets reabsorbed back into the body

Countercurrent multiplier system

• Loop structure

• Describes how fluid is always flowing in the kidneys in different directions

• Osmotic gradient that allows for reabsorption to occur in nephrons

• Reabsorption and allows for concentration of (water/salts) in urine

Descending Loop of Henle

• Passive permeable to water

• Water reabsorption occurs here

Ascending Loop of Henle

• Active transport of sodium & chloride follows passively

• Impermeable to water

• There are high amounts of cholesterol in the cell membrane, preventing water from passing

• Na+/K+ ATPase pumps will pump sodium, potassium, and chloride out into the interstitial space. This will increase the concentration outside of the cells and increase the osmolarity → water is then able to be drawn out of the cell

Effects of urea

• Urea contributes to high osmolarity in medulla → deep region of collecting duct is permeable to urea & transports it

• Urea protects RBCs from hyperosmotic/hypertonic solution in the vasa recta (the solution can cause swelling/cell explosion)

  • Urea goes into RBCs and leave them allowing them to survive in the vasa recta

Significance of Reabsorption

• 85% of filtered H20 and salts are reabsorbed early in tubule system

• This is constant and independent of hydration levels

• The remaining 15% (27 L) is reabsorbed variably, depending on level of hydration and is controlled by the release of hormones

3 renal function processes

Filtration, reabsorption, secretion

Filtration

• Blood under pressure forces plasma (ie filtered blood) into bowman’s capsule.

• Fluid at this stage is called “glomerular filtrate” contains electrolytes, water, but no large proteins (in healthy kidney)

• A protein/cell-free plasma

Rate of filtration

180 L/day

Secretion of Drugs

• Many drugs, toxins, and metabolites are secreted by organic anion transporters (these are non-specific transporters) of the PCT

• Benefit = Gets rid of toxin & metabolites; Con = Gets rid of medication that we need in our body

• Involved in determining half-life of many therapeutic drugs

• “Organic Ion Secretory System”

Aldosterone

• Minerealcorticoid released from adrenal cortex

• Also a steroid

• Controls levels of minerals/salts (Na+, K+, Cl-)

• Causes =

  • A decrease in blood potassium levels (low potassium)

  • A high rate of urinary sodium reabsorption, which will produce an increase in the volume of blood

• 2 main reasons for production

  • Decrease in blood volume

  • Decrease in blood Na+ levels

  • These mechanisms will activate the “Renin-Angiotensin System” that will stimualte the adrenal gland to release aldosterone

Na+, K+, H+ Relationship

• Na+ reabsorption in distal convoluted tubule and collecting duct createss electrical gradient for H+ & K+ secretion

• When extracellular H+ increases, H+ moves into cells causing K+ to diffuse out & vice versa

  • Hyperkalemia can cause acidosis

• In severe acidosis, H+ is secreted at expense at expense of K+

Hormonal Regulation of water reabsorption

• Antidiuretic hormone (ADH), also known as vasopressin, is secreted from the posterior pituitary

• The most important effect of ADH is to conserve body water by reducing the output of urine

• ADH causes the insertion of “water channels” or aqua porins, into the membranes of the collecting duct. These channels transport water through tubular cells & back into blood, thereby retaining water in the body

What causes vasopressin release?

• Dehydration

• Salt ingestion

Renal Acid-Base Regulation

• Kidneys help regulate blood pH by excreting H+ &/or reabsorbing HCO3-

• Most H+ secretion occurs across walls of PCT in exchange for Na+ (Na+/H+ antiporter)

• Normal urine is slightly acidic (pH 5-7) because kidneys reabsorb almost all HCO3- & excrete H+

• Reabsorption of HCO3 in apical membranes of PCT cells are impermeable to HCO3-

Reabsorption of HCO3 in PCT

• Neither HCO3- nor H+ can be reabsorbed in their ionic forms

• HCO3- can be reabsorbed if converted back to carbonic acid

• The enzyme carbonic anhydrase (CA) is found on the apical surface & within the cells of PCT

Renal Clearance

• Refers to ability of kidney to remove substance from blood & excrete them in urine

• Actual clearance (excretion) of a compound is a result of the amount filtered — what is reabsorbed + what is excreted

• Excretion = Filtration - Reabsorption + Secretion

• For any individual compound, renal clearance can be calculated as the volume of plasma that is “cleared” per unit time

Inulin Measurement of GFR

• Inulin = A fructose polymer that’s useful for measuring GFR because it is neither reabsorbed or secreted

• Rate at which a substance is filtered by the glomerulus can be calculated

  • Quantity filtered = GFR x P (inulin concentration in plasma)

  • Quantity excreted = V (rate of urine formation) x U (inulin concentration in urine)

• If there is no reabsorption or secretion of a substance then → Amount filtered = amount excreted

Renal Plasma Clearance (RPC)

• RPC = (V x U) / P

• If substance is filtered but not reabsorbed then all filtered will be excreted — RPC = GFR

• If substance is filtered & reabsorbed then RPC < GFR

• If substance is filtered but also secreted & excreted then RPC will be > GFR (= 120 mL/min)

Clearance of Urea

• Urea is freely filtered into glomerular capsule

• Urea clearance calculations demonstrate how kidney handles a substance: RPC = V x U/P

  • V = 2 mL/min

  • U = 7.5 mg/mL of urea

  • P = 0.2 mg/mL of urea

  • RPC = 75 mL/min

• Urea clearance is 75 mL/min, compared to clearance of inulin = 120 mL/min

• Thus 40-60% of filtered urea is always reabsorbed

Measurement of renal blood flow

• Not all blood delivered to glomerulus is filtered into glomerular capsule

  • 20 % is filtered; Rest passes into efferent arteriole & back into circulation

  • Substance that aren’t filtered can still be cleared by active transport (secretion) into tubules

Total Renal Blood Flow using PAH

• PAH clearance is used to measure total renal blood flow

• Normally averages 625 mL/min

• It is totally cleared by a single pass through a nephron → must be both filtered & secreted

• Filtration & secretion clear only molecules dissolved in plasma

  • To get total renal blood flow, amount of blood occupied by erythrocytes must be taken into account

  • 45% is RBCs, 55% in plasma

  • Total renal blood flow = PAH clearance/0.55