Lecture 15, 16, 17: The Kidneys!

Describe the basics of the kidneys

• The left kidney is higher than the right because the liver pushes down the right kidney

• Adrenal glands and kidney have no communication with each other  

• Kidneys get 20% of your blood 

  • Abdominal aorta → renal artery 

• Venous drainage 

  • Renal vein (the renal artery is just behind the renal vein) → inferior vena cava 

• Urete goes to bladder and then through the urethra 

Describe the parasagittal view of the kidneys

• Renal capsule → to hold in the pressure 

• Perirenal fat → to hold it up in place and together, also holds adrenal cortex 

• Renal fascia → also attaches to liver and respiratory 

• Pararenal fat 

Describe the renal cross section

• Renal fascia 

• Perirenal fat 

• Pararenal fat 

• You hold on to the fat, very hard to lose 

Describe the renal hilum

• Renal artery

• Renal vein 

• Ureter

Describe the inside of the kidneys

• Renal cortex 

• Renal column

• Renal pyramid  

• Renal medulla = all the renal pyramids 

Describe the urine pathway

1. Nephron – Urine is produced here. 

2. Collecting Duct 

3. Renal Papilla

4. Minor Calyx 

5. Major Calyx 

6. Renal Pelvis

7. Ureter

8. Bladder

Describe developmental problems and pathologies for the kidneys

• Polycystic kidneys

• 4 ureter (2 for every kidney) 

• The kidneys are hung together → horseshoe kidney 

• Ureter is extremely distended → hydronephrosis (swelling of ureter)

Describe the mystery of the kidneys

• 20-25% of blood goes to kidney, but kidney is only 1-0.5% of the body weight 

• From 20-25% → 180 L is made into filtrate by the nephron, however filtrate has virtually no protein or formed elements of the blood or any large molecule. 

• Even though filtrate has a lot of small molecules like glucose, amino acids, and bicarbonate ions, the urine has basically no protein, glucose, or bicarbonate. 

• Out of 180 L of filtrate, only 1 L of urine is made in a day (99% is reabsorb) 

Describe the circulation of the nephron

• Afferent arteriole → blood goes in 

• Efferent arteriole → blood goes out

• Peritubular capillaries 

• Blood goes back to the venous circulation 

Describe the parts involved in filtration

• Renal corpuscle → filtrate making machine 

• Glomerulus → make filtrate 

• Renal tubule → makes filtrate into urine 

  • Reabsorption of material from the filtrate in the tubule to the blood (ex. glucose) 

  • Secretion of material from the blood to the tubule (ex. Drugs and penicillin) 

• Collecting duct → collects and concentrate the urine 

Describe the juxtaglomerular apparatus

• Macula densa 

• Granular cells 

• Mesangial cells  

• Sympathetic nerve on the afferent arteriole → constrict arteriole to prevent peeing

Describe the renal corpuscle function

• The glomerular capsule is a continuous layer of tissue with the glomerular capillaries jammed into the centre 

• The space between the visceral and parietal layer is the capsular space, and that is what the filtrate is formed 

• Afferent blood comes in and pressure in the capillaries make filtrate into the capsular space 

Describe the relationship between the heart and the kidneys

• The kidneys work in partnership with the CV system 

  • The CV system generates the pressure for glomerular filtration and drives the high flow needed to maintain a stable cortical interstitial solute composition. 

  • The kidneys…

    • Maintain blood volume 

    • Regulate plasma osmolality

    • Secrete mediators 

    • Affect both cardiac performance and vascular tone

Describe net filtration pressure

• Pressure pushing fluid out of the glomerular capillaries → positive pressure 

  • Blood, hydrostatic pressure in the capillaries

• Pressures holding fluid in the glomerular capillaries → negative pressures 

  • Capsular hydrostatic pressure (i.e. the presence of fluid already in the capsule) 

  • Blood osmotic pressure (i.e. the attraction of the dissolved materials in the blood for water) 

• Usually a net positive pressure of 10 mm of Hg. 

• This pressure is what pushes filtrate into capsular space and determines the glomerular filtration rate (GFR) 

Describe auto-regulation of the glomerular filtration rate (GFR)

• Kidney itself can act to alter the GFR by autoregulation and are normally trying to maintain a GFR 

• The GFR is easily altered by changing the blood pressure in the glomerulus or the leakiness of the capillaries of the glomerulus 

• The changes in the glomerulus pressure are done by the myogenic mechanism or tubuloglomerular feedback 

Describe the myogenic mechanism

• The smooth muscle of the afferent arteriole is stretched by the increase in blood pressure and afferent arteriole responds with constriction which decreases GFR. 

Describe the tuboglomerular feedback

• The macula densa of the juxtaglomerular apparatus detects high amounts of filtrate flow (i.e. lots of water and Na+ and Cl- flowing past) an increases adenosine release which causes Ca2+ release and constructs the afferent arteriole which decreases GFR. 

1. High concentration of flow of Na+ 

2. Increase in adenosine 

3. Constriction of afferent arteriole 

Describe hormone regulation of GFR

• Atrial natriuretic peptide (ANP)

  • Made in the atrium of your heart. 

  • Distension of the atrium of the heart loads to the release of ANP 

  • Relaxation of the mesangial cells between the glomerular capillaries, which becomes more spread out and relaxed so more filtration can occur. 

  • ANP also relaxes afferent arteriole of the glomerulus and increases Na+ loss 

• Angiotensin II 

  • Decreases GFR, because it constricts afferent arterioles.
    However, it increases blood pressure because it constricts systemic arterioles. 

  • Angiotensinogen –(renin)→ Angiotensin –(ACE)→ Angiotensin II 

Describe angiotensin and BP

• Decrease in blood pressure/sympathetic nervous system stimulation 

• Juxtaglomerular apparatus senses that and releases renin 

• Which creates angiotensin II 

• Constriction of systematic and glomerular afferent arterioles 

• Blood pressure increases (negative feedback, turns off loop) 

Describe neural regulation of GFR

• The sympathetic branch of autonomic nervous system has inputs muscular walls of the afferent arterioles 

• The receptors are alpha1-adrenoceptors just like most of the rest of the arterioles in the body 

• WIth low blood flow, the glomerular hydrostatic pressure goes down and then filtration decreases 

Describe renal filtration in terms of GFR

1. Sympathetic stimulation/Low BP 

2. Increase in renin release 

3. Increased BP from more angiotensin II and more Na+ reuptake in tubules. 

What do we do with 180 L of filtrate

• Completely absorbed → glucose, AA, bicarbonate ion 

• Regulated and thus is reabsorbed → water, sodium, potassium, chloride 

• Excreted as waste → urea, creatinine, drugs, and drug metabolites 

What is gained and lost between filtrate and urine?

• 180 L of water in filtrate → 1-2 L of urine 

• 162 g of glucose in the filtrate → but none in the urine 

• 570 g of Na in the filtrate → but 4 g excreted 

• Uric acid 8.5 g in filtrate → 0.8 g in urine 

• Creatinine 1.6 g in filtrate and 1.6 g in the urine 

• Beyond the renal corpuscle the nephron is completely consumed with regulating these substances 

Describe the blood supply/drainage of the renal tubules

• Renal arteries 

• Lobar arteries

• Arcuate artery 

• Branches into radial arteries 

• Coming off of that are afferent arteries 

• Capillary bed between afferent arteries and efferent arteries 

• Goes to venous drainage in arcuate vein 

Describe how water/molecules move through the membrane

• Reabsorption can occur by either 

  • Active transport → requires energy 

  • Passive transport → chemicals following their electrochemical gradients 

• The movement of water is by osmosis 

  • Passive mechanism by which water follows its concentration gradient through  semipermeable membrane 

Describe passive transport

• Does not need energy 

• Paracellular route → some solutes can slip between the tight junctions of the cell 

• Transcellular route → Into/out of the cells of the tubules by following electrochemical gradients (most common) 

• Diffusion may be facilitated by transport proteins in the movement of glucose from inside of the tubular cells to the interstitial fluid 

• Leakage channels also exist for some ions to facilitate their walk down the concentration gradient

What if the kidneys fail?

• Salts (Na+, K+, Ca2+, and Cl-, all electrolytes) and waste products like urea build up and the pH of the blood goes down 

• Massive edema results from salt retention 

• Acidemia results from the inability to excrete acids 

• When potassium levels get too high (hyperkalemia) then cardiac arrest occurs 

Describe therapeutics for kidney failure

• Hemodialysis 

• Peritoneal dialysis 

• Kidney transplant 

Describe peeing

• Ureter 

• Derusor muscle → bug smooth muscle that expels urine 

• Ureteral opening 

• Urethral opening 

• Triangular area called trigone that does not contract 

• External urethral sphincter 

  • For females, it goes ⅓ up urethra 

  • For males, has additional internal sphincter at the neck of the bladder isolate prostate from bladder so that during ejaculation, the semen does not go backwards

  • Sits in deep transverse perineaus muscle 

• Levator ani → 3 muscles working together, because urethral sphincter is under your control, when the levator muscles pull, they help close 

• Pubic sphincter, external urethral a sphincter, and levator ani all work together to close your urethra

Describe the micturition reflex

• Bladder fills about 200-400 ml of urine, the stretch receptors in the bladder wall are stimulated and send messages to the sacral portion of the spinal cord 

• Sensory input to this level triggers an autonomic reflex which sends parasympathetic motor signals to the detrusor muscle (a smooth muscle) to contract and the internal urethral sphincter (in males) to relax. 

  • Internal sphincter is made of smooth muscle, thus regulated by ANS and not under voluntary control

• The external urethral sphincter (in males and females) is striated muscle and thus can be consciously controlled. 

• Other muscles like the levator ani and deep muscles of the perineum can help too. 

• The somatic nerves holding this sphincter closed are inhibited by the micturition reflex → pressure build up is usually not enough to open the external sphincter. 

• In adults → conscious effort to relax the external sphincter before urine can pass through (although this does not last forever) 

Describe diuretics (water pills)

• Furosemide (LASIX) work by inhibiting the Na+-K+2CL- pumps in the ascending loop of Henle. 

  • This means less ions are pumped into the interstitial fluid and thus less fluid is pulled out of the descending limb of the LOH and more urine. 

List hormonal ways to regulate tubular reabsorption

• Antidiuretic hormone

• ADH aka vasopressin

• Angiotensis II and BP

How to measure kidney function

• Urinalysis and performing blood tests

• Urinalysis analyzes the volume, physical, chemical, and microscopic properties of urine 

• Blood analysis involves looking at the levels of waste products 

Describe blood urea nitrogen (BUN)

• Measure of urea nitrogen which is produced due to protein breakdown and usually excreted by the kidneys 

• BUN will increase in the blood when the GFR decreases sharply (renal disease), and urine production is low such as with dehydration. 

Describe plasma creatinine

• Waste product from breakdown of creatine phosphate in the skeletal muscle. 

• Normally the levels remain steady in the blood since urine excretion equals its discharge from muscle. 

Describe renal clearance

• How much material is going out of the urine → how quickly the kidneys are removing a substance from your body

• Drugs are often cleared by the kidney, so you need to know how much is going out to know how much to put in 

• Ex. antibiotics are excreted renally, for example penicillin can become dangerous for someone with kidney failure because they cannot get rid of the drug

Describe high and low renal clearance

• High renal clearance indicates efficient excretion of a substance from plasma to urine (e.g. penicillin, metformin) 

• Low renal clearance indicates low excretion from plasma to urine (e.g. glucose) 

Describe first order process

• The more there is to do, the more the body works on it → first order process 

• Contrast: alcohol, you clear 1 drink per hour which is not a first order process 

  • You saturate the enzymes in the oliver, but drinking more doesn't make the process faster because it is not a first order process. 

  • This means 8 drinks cleared in 8 hours 

Describe GFR

• Measure of the rate of blood filtration by the kidneys. GFR is determined by the flow from the plasma into the glomerular capsular space. 

• To estimate this, you need a substance that is not reabsorbed nor secreted by tubules so renal clearance is equal to GFR. Inulin (not insulin) is one example. 

• GFR can be measured by injecting inulin and measuring rate of urine output and concentrations of inulin in the blood and urine. 

• Creatine is usually used for GFR measures though a tiny amount is reabsorbed by tubules. Inulin is typically used for specialized studies.