Structure and Function of the Kidneys

Functional unit is the nephron

Function: Regulation of extracellular fluid by urine formation

Regulates:

1.        Blood volume/blood pressure

2.        Concentration of wastes

3.        Concentration of Na+, K+, HCO3-

4.        pH of plasma

Structure: 2 kidneys below diaphragm

Size of a fist

Renal Pelvis-Ureters-Urinary bladder.

Cortex

Medulla composition:

8-15 renal pyramids, separated by renal columns

Calyces join to form renal pelvis

Kidney stones:

1.        Calcium oxalte

2.        Calcium phosphate

3.        Uric Acid

4.        Cystine

Crystals and proteins pass from calyces and block urine in ureter causing  pain.

Urethra is 4 cm in women, 20 cm in men

2 sphincters: upper internal urethral sphincter

Voluntary: lower external urethral sphincter.

Micturition Reflex: urination.

Reflex center at 2,3,4 sacral levels of spinal cord. Internal relaxes, urgency and external relaxation is under voluntary control. Ability develops at 2-3 years of age.

Microscopic Structure of Kidney

Each kidney has 1 million nephrons

Renal Blood Vessels

Arterial blood, renal artery, interlobar arteries, Arcuate arteries, interlobar arteries, afferent arterioles, glomeruli efferent arteriole, peritubular capillaries, interlobar veins, arcuate veins, interlobar veins, renal vein, inferior vena cava

Nephron

Glomerular capsule: in cortex, Bowman's Capsule

Proximal Convoluted tubule: in cortex,  Cubodial cells with lots of microvilli

Loop of Henle: in medulla

Descending limb

Ascending Limb

Distal Convoluted Tubule: cortex

Collecting Duct

Juxamedullary nephrons: Originate in inner 1/3 of cortex. Longer loops.

Cortical nephrons: originate in outer 2/3 of cortex

Polycystic Kidney disease: develops in middle age, autosomal dominant trait. Cysts on renal tubules.

Urine collects in collecting duct, minor calyx, renal pervis-ureter.

Glomerular Filtration

Glomerular capillaries have pores (fenestral)

RBC, WBC, platelets can't be filtered.

Inner layer of glomerular capsule are cells called podocytes (shaped like octopus) which form a web like clasped hands, which wrap the capillaries forming slits as passageway for filtered molecules.

Proteins don't usually go into filtrate.

Glomerular Ultrafiltrate

Net filtration pressure is 10 mmHg

Due to large surface area of glomerular capillaries a lot of filtrate is produced

Glomerular filtration rate(GFR) Volume/minute of both kidneys.

115ml/min women, 125ml/min in men.

All blood filtered every 40 minutes, 180L/day…water is reabsorbed.

Regulation GFR

Vasoconstriction or vasodilation of afferent arterioles

Extrinsic: Sympathetic innervation

Intrinsic regulation mechanism: renal autoregulation

Sympathetic Nerve Effects

Constriction of afferent arterioles.

Renal Autoregulation

MAP may change but GFR does not.

Pressure changes direct constriction or dilation of afferent arterioles.

Increase in filtrate volume sensed at ascending limb. Increase in fitrate=constriction.

Called tubuloglomerular feedback.

Reabsorption of Salt and Water

Water follows salt by osmosis

Most salt and water reabsorbed at proximal tubule

Remaining water reabsorbed at collecting duct.

180 L of filtrate produces 1-2 Liters of urine in 24 hours.

1% of filtrate is excreted.

400ml urine/day is minimum

Since the filtrate solute concentration is the same as plasma solute concentration (300mOsm) solutes need to be reabsorbed to blood.

Proximal Tubule

Has lots of microvilli and mitochondria

Active and Passive Transport

Basal and lateral sides of cells have Na/K pumps that keep Na concentration low in the cell.

NA+ diffuses into apical side of cell. Cl- passively follows.

Water follows salt.

All returns to blood.

65 % of salt and water in filtrate is returned at proximal tubule.

20 % returned at Descending limb, no hormonal control, 6 % of energy expense.

15% returned later and hormone are involved.

Countercurrent Multiplier System

The renal medulla is 4 x as saltly as the filtrate due to juxtamedullary nephron

Ascending  Limb: extrudes salt

Sodium diffuse out

K+, and CL- moves by secondary active transport.

Na+ actively transported to interstial fluid.

Not permeable to water.

Descending Limb(20 % of salt and water returned to blood here)

Not permeable to salt

Permeable to water.

Water leaves via diffusion.

Countercurrent Multiplication

As you move from cortex to medulla, it gets more and more salty. This is a feature of the descending(water leaves) and ascending loop moving in opposite directions, and the active extrusion of salt from the Ascending  limb.

Vasa Recta: capillary-like

Maintains the salt concentration by removing the water that comes out of filtrate, but leaving the salt in the medulla.

Urea transporters

Aquaporin proteins

Countercurrent exchange: attracts water but extrudes urea and salt out at ascending limb.

Urea

Extruded from thin segment of loop of henle and collecting duct.

Collecting Duct: ADH

Collecting duct impermeable to salt but is permeable to water. Urine is hypotonic compared to interstitial fluid in this region.

Water returned to circulation.

The rate of water reabsorption at this region determined by water permeability of collecting duct.

This depends on the number of aquaporins.

1.        ADH binds to receptor proteins on collecting duct.

2.        cAMP is activated.

3.        Exocytosis of vesicles from golgi that have aquaporins.

4.        No ADH the aquaporins are removed via endocytosis.

Osmoreceptors in hypothalamus trigger ADH release from Posterior Pituitary.

Diabetes insipidus is when not enough ADH secreted.

Renal Plasma Clearance

Waste is removed from blood.

Tubular Secretion

Secretion is the active process of eliminating wastes/toxins by passing them to urine.

Drugs

Proximal tubule has receptors that will select a variety of products to be eliminated.

Some drugs block secretion of antibiotics and increase effectiveness of these drugs.

GFR

Inulin a polymer of fructose is used to measure GFR. It is not reabsorbed or secreted.

Quantity excreted per minute mg/min=V ml/min x Umg/ml

Quantity filtered per minute mg/min=GFR ml/min x Pmg/ml

GFR x P = V x U

GFR= V X U/P

Inulin 120 ml/min clearance

Creatine used to check GFR in practice.

Calculations

Renal Plasma Clearance is volume of plasma from which substance totally removed in one minute by kidney.

Renal Plasma Clearance = V xU/P

Urea Clearance

75ml/min

Some urea is reabsorbed

PAH

Measurement of renal blood flow

It is possible for all of a substance to be cleared in a single pass even though not all blood is filtered. This occurs by secretion. PAH is a substance that can be cleared. 625 ml/min.

Take into account that RBC take up space in blood. Calculate volume and divide by plasma volume to get the total real blood flow.

Glucose

Glucose and amino acids are reabsorbed at proximal tubule.

Carrier mediated transport can become saturated.

Transport maximum.

Normally only 125 mg/min of glucose in tubules.

325 mg/min is transport maximum.

When glucose is 180 mg per 100ml glucose gets into urine.

Called renal plasma threshold for glucose.

Normal glucose is 1mg/ml.

Diabetes mellitus is when there is not enough secretion of insulin

Lots of urine to help get glucose out.

Electrolyte and Acid-Base Balance

Kidneys regulate

Na+--important for regulation of blood volume and pressure

K+--important for regulation of cardiac and skeletal muscles.

Hco3-

H+

 

Aldosterone(Adrenal cortex)

90 % of Na and K reabsorbed before distal tubule.

Cortical collecting duct and distal tubule reabsorb varying amounts depending on need.

Controlled by Aldosterone.

Sodium reabsorption

30 g Na secreted in urine per day, unless aldosterone involved.

Max aldosterone secreted, then NO NA in urine!

Mostly occurs at cortical collecting duct.

Potassium Secretion

  1. Depends on the amount of Na in distal tubule and collecting duct.
  2. Aldosterone

High K in blood stimulates Aldosterone secretion

Increase in Na reabsorption and secretion of K increases.

Diuretics increase Na secretion at distal tubule. This increases K secretion and loss.

Wrong amount of K leads to heart problems.

Aldosterone Secretion

Promotes Na retention

K loss

Concentration of Na and K changes aldosterone secretions.

Juxtaglomerular Apparatus

Afferent arteriole comes in contact with ascending limb of loop.

Cells in this region secrete renin.

Angiotensinogen converted to angiotensin 1 by renin.

Angiotensin 1 converted to angiotensin 2 by ACE.

ACE in lungs.

Angiotensin 2 stimulates adrenal cortex to secrete aldosterone.

Renin Secretion

Not enough salt in diet leads to a fall in blood volume.

Decreased blood volume causes increased renin secretion.

Granular cells are baroreceptors.

Sympathetic nervous system can stimulate this when it detects decrease in blood volume.

Good example of negative feedback (retain more Na, blood volume rises).

Macula Densa                                                                     

Cells in ascending limb called macula densa can inhibit renin secretin when blood Na is raised.

Atrial Natriurectic Peptide

Increase in blood volume stretches atria and increases ANP.

ANP promotes the excretion of Na and water in urine

Endogenous diuretic

Sodium, potassium, and H+

K+ concentration and H + concentration are related

Extracellular H+ concentration goes up, and H+ moves in to cell

K+ then moves out.

In Distal tubule and cortical collecting duct, K+ and H+ secreted to urine when Na+ reabsorbed.

When acid blood, then more H+ secreted, but not as much K+ leading to too much K+ in blood.

When K+ secreted not enough H+ is secreted.

Not enough K+ it can be reabsorbed by collecting duct.

Addison's disease is not enough aldosterone (which would promote secretion of K+ and H+) leads to acidosis and hyperkalemia.

Acid-Base regulation

Excrete H+ and reabsorb bicarbonate.

H+ goes in filtrate, is secreted at proximal tubule(antiport with Na+).

In filtrate bicarbonate turned to CO2 which diffuses into apical cells and turns back to bicarbonate.

High elevation: Low Pco2, alkalosis

Excrete bicarbonate

pH lowers.

Inhibit renal carbonic anhydrase,

Stop reabsorbtion of bicarbonate

Treat Acute Mountain Sickness

Buffers

H+ in urine buffered by HPO4 2-(H2PO4) , and NH3(ammonium)

Diuretics

Lower blood volume with diuretics

Hypertension, congestive heart failure, edema

Loop diuretics: most powerful, stop Na+ movement out of loop,

Thiazides: stop salt and water reabsorption at distal convoluted tuble.

Carbonic anhydrase inhibitors: stop bicarbonate reabsorption and water that goes with it. Weak.

Osmotic diuretics: extra solutes in filtrate

Potassium-sparing diuretics: Aldosterone agonist, or blocks Na+ reabsorption and K+ secretion

If you don't have enough K+ you have heart problems and neurological problems. Supplement diuretics with K+ supplement and low salt diet.

Renal Function Tests and Kidney Disease

Real plasma clearance of PAH

Measurement of GFR via inulin clearance

Creatine concentration in plasma

Urinary albumin levels--hypertension and diabetes can damage the kidney.

Acute Renal Failure

Sudden loss of ability to excrete waste, regulate blood volume, pH and electrolyte balance.

NSAIDS can cause this as can reduced blood flow, inflammation, atheriosclerosis.

Glomerulonephritis

Strep infection

Autoimmune response

Damage to glomerula

Protein leak into urine.

Edema.

Renal Insufficiency

Leads to hypertension

Uremia

Acidosis

High K+ concentration

Uremic Coma

Dialysis

CAPD in patients abdomen