Introduction to Human Physiology - 9 Urinary System

Source: My personal notes from Introduction to Human Physiology | Coursera

In this module, we turn our attention to the urinary system and specifically to the functions of the kidney, a filter of the blood. The kidney is a complicated organ whose actions integrate with those of the cardiovascular system to maintain blood pressure and with the respiratory system to maintain acid-base balance. As we progress through this module, we consider the mechanisms by which the kidney regulates the water content and the electrolyte content of the body. We focus on the roles of the normal kidney but also consider changes in homeostasis due to either disease or drugs. The last lesson of this module considers the role of the kidney in regulating acid-base balance of the body and its integration with the respiratory system.

Structure and Function

Structure of kidney and the homeostatic functions. Balances water and electrolytes in body.

Kidney nephron filters blood. Different regions of the kidney have functions.

Kidney Structure

• There are two kidneys, they are connected by tubules (ureters) connected to the bladder.

  • Located near back of body
  • Capsule surrounds kidney
  • Renal cortex on outer area, renal medulla on inside
  • In “indentation” of kidney (like a mushroom), vein and artery and ureters is there.
  • Filters are in the kidney, they are called nephrons

• Function: filter blood and balance electrolytes (Na, Ca, K, protons (pH balance), etc.)

• Endocrine hormones:

  • Erythropoietin hormone during hypoxia
  • Renin in response to hypotension, low blood pressure
  • Vitamin D3 activation, works in GI tract to absorb Ca for calcification of bone.

Nephron Structure

Filtration units for blood

• 2 capillary beds connected by arterioles.
• Blood enters and exits via glomerulus
• Renal tubules drains into collecting duct #5, which connects to ureter
• Note distribution in cortex and medulla.
• Loop of Henle has:
  • Descending (thin loop of Henle)
  • Hairpin turn
  • Ascending (thick ascending loop of Henle)

Two Types of Nephrons

• 90% of nephrons are *cortical nephrons w*hich are mostly in cortex
• Juxtamedullary nephron means “next to” medulla nephron.
  • They have standing osmotic gradient from 300 - 1200 to mOsM in the interstitial fluid. Needed for concentration of urine.

Regional Changes in Volume and Osmolarity

Blood coming through renal artery is 1 L / min of cardiac output

• It filters fluid phase of blood which is the plasma. Plasma is 60% of the blood. Rest are blood cells. So about 600mL/min is filtered

• About 0.5 - 1.5 L / day of urine is generated. Majority of filtrate is moved back into the body to keep cardiovascular system moving.

• Note that mOsM changes:

  • 300 mOsM = same as plasma

  • 50 - 1200 mOsM for urine. Dilute urine for good hydration, concentrated urine for dehydration

Regional Functions

A diagram of a renal tubule plus vascular system

Two arterioles:

• Afferent (entry)
• Efferent (exit)
• Portal system around glomerulus (afferent and efferent arterioles)
• Tubule extends from Bowman’s capsule.
• There is exchange from capillaries to interstitial fluid to kidney lumen and reverse (E and F)
• Blood can secrete into the tubule directly, bypassing filtering (S)
• Urine is excreted (E)

Filtration Rate and Regulation

Filtration - filtrate (what is being filtered)

Glomerular filtration rate (GFR)

Autoregulation

Renal blood flow and GFR regulation

Filtration load

Glomerular Filtration Rate and Clearance

Glomerulus = capillary nears Bowman’s capsule (BC).

F = filtrate

R = reabsorption

S = secretion

C = Clearance

• Inulin (large polysaccharide) allows measurement of GFR as it is filtered and secreted and not reabsorbed over time.

Checking clearance against inulin determines a solutes absorption/secretion.

Net Filtration Pressure

Kidney filters out small particles only and leaves large molecules and cells inside blood. It allows ions and water to flow past barrier.

HPg = Hydrostatic pressure in glomerulus

Oncotic Pg = attraction of water into blood

HPbc = hydrostatic pressure in Bowman’s Capsule

Control of Filtration

• Glomerulus only filters a portion of blood.

• Higher pressure for afferent arteriole (aff art.) increases GFR.

• Constriction of aff art. Decreases GFR.

• Constriction or dilation of aff and eff arterioles affect GFR and can balance each other.

Autoregulation of Blood Flow and GFR

Kidney is filtering the blood at all times.

Renal function can operate independent of mean arteriole pressure (MAP) thanks to autoregulation.

Myogenic response = stretch of arterioles, generates response to contract muscles

Tubulo-glomerular feedback = tubule sends feedback to Glomerulus

F = flow

Tubulo-Glomerular Feedback

Macular Densa (MD) detects flow of filtrate and sodium.

• When low flow, MD through paracrine signalling causes vasodilation (smooth muscle relaxation) and more filtration.

• Local control

Juxtaglomerular (JG) cells are also endocrine cells and cause detection of low blood flow. The MD is like a detection of low mean arteriole pressure in the local system.

Reflex Actions alter GFR and Renal Blood Flow

Exercise lowers GFR due to increase vascular resistance.

Hemorrhage (blood loss), lowers GFR to allow more blood to go to brain and heart.

Filtration Load of the Freely Filtered Substance

How much of a filtered substance is filtered?

Using the GFR and concentration of the substance in blood allows the calculation.

Note for the glucose example, even though 125 mg/min are filtered, very little is secreted as most is absorbed in the PCT.

* Regulation of Fluid Balance

• Know location of juxtamedullary nephrons

• Permeability along the renal tubules for ions and water

• Osmotic gradieent

• Renal - Angiotensin - Aldosterone System (RAAS)

• ECF volume and hormone regulations

• Diuresis

Osmolarity and Volume in Tubules

Typical daily intake is 2 L.

Kidney regulates fluid, ions, and solutes. It cannot make water.

Tubule Permeability to Solute and Water

juxtamedullary nephrons and osmotic gradient

• Medulla interstitial area is 600 mOsM. In TLH, water in tubule moves into medulla due to aquaporin channels.

• Filtrate (fluid inside tubule lumen) is concentrated at hairpin turn of Henle.

• In TAL, there are no aquaporin channels, but there is permeability to ions. A hypotonic solution is the result (low osmolarity).

• What happens to water absorbed in the TLH and ions in the TAL?

  • It is absorbed back into the capillaries (para tubular capillary). Notice the capillary bed is in reverse direction as the tubule flow in the loop of Henle. The second capillary bed in the medulla is the vasa recta. Eventually blood is 300 mOsM and isotonic to rest of body.

Pathology - Diabetes insipidus

• Lots of urine since DCT and CD has no aquaporin channels and water cannot move out into the medulla.

Diagram of tubules and regions named below.

Vasopressin (ADH) Function

Antidiuretic hormone (ADH) - increase water retention via aquaporin channels at distal convoluted tube and collecting duct. Happens because of osmotic gradients.

Aldosterone Function

Secreted by adrenal glands in response to high [K] and angiotensin due to low blood volume.

Increases Na+/K+ ATPase and Na transporters. Moves Na into the body and the water that follows.

Renal - Angiotensin II - Aldosterone System (RAAS)

1. Renin (an enzyme) secreted by kidney (cells next to the glomerulus) due to low plasma volume

2. Renin enters plasma to cleave to form a protein = Angiotensin (ANG) I, Angiotensin II is formed by ACE (Angiotensin Converting Enzyme). Increase aquaporin channels. Angiotensin II causes aldosterone secretion which increases Na absorption and water that follows.

3. Vasoconstriction is caused by hormones ANG II and ADH.

4. Helps in preload to increase cardiac return, increases total peripheral resistance.

Excess Volume

What happens when you take in more fluid than you can excrete?

Your blood osmolarity drops, ion gradients are disrupted. ECF is dilute, so cells swell with water due to osmotic gradient.

• Turn off ADH. No aquaporin channels in tubules - like diabetes insipidus.

• Atrial stretch causes secretion of Atrial Natriuretic Factor (ANF) and kidney stretches. Filters are enlarged, causing more water loss.

• Increased Glomerular filtration rate (GFR). GFR is a test used to check how well the kidneys are working. Specifically, it estimates how much blood passes through the glomeruli each minute. Glomeruli are the tiny filters in the kidneys that filter waste from the blood.

Body tries to increase GFR and urine, but if fluid intake is too high, e.g. brain neurons swell, it can become lethal.

Diuresis

High water loss from several situations (applies with water loss is > 1mL/min).

Osmotic diuresis example: diabetes mellitus

Diurectics examples: caffeine, it mildly inhibits NaCl transporter

Reabsorption and Secretion

Peritubular capillary

Cellular mechanism for transport of glucose and bicarbonate

Transcellular vs. paracellular pathways, ion drag

Transport rate and thresholds

Secretion

Proximal Convoluted Tubule (PCT) Functions

2nd capillary on top of diagram is the peritubular capillary

Reabsorption and secretion are critical to keeping water and ions balanced in body.

Portal System and Pressure Gradients

Nephron is shown at bottom of diagram

• Notice that Bowman’s capsule always has hydrostatic pressure > oncotic pressure

• In PCT, oncotic pressure greater, allowing reabsorption

Reabsorption in Proximal Convoluted Tubule (PCT)

Small interstitial space between basal side of tubule and capillary (interstitial space = IS)

• Glucose and Sodium cotransporter = Glc Na is shown

  • Facilitated by diffusion via Na/K ATPase and Glucose diffusion in basal region.

  • Osmotic gradient created and water follows Glc, Na and other solutes going through region.

• Carbonic anhydrase is occurring in lumen and in cells.

  • Bicarbonate, Cl- antiporter on basal side.

  • Facilitated by antiporter since H+ is excreted into lumen in exchange for Na+ and Na/K ATPase

Rate of Transport

Transport can be saturated since it is not just diffusion, but using transporters. (All trucks are in use).

When all transporters are in use for a substrate = “at threshold”, substrate will be found in the urine.

• Diabetes mellitus have high blood glucose, so glucose transporters are saturated. Glucose then travels in the collecting duct without being reabsorbed causing urination and frequent loss of water.

Terms

Paracellular movement

• tight junctions between kidney tubule cells and interstitial space towards the blood are “leaky”.

• Water is able to leak from the lumen, going into the blood.

• K+ can also leak –> Solvent drag is the paracellular movement of K+

Secretion in Proximal Convoluted Tubule (PCT)

• Organic compounds will use generic transporters (2nd secondary active transport) on basal part of cells. Since they are only on the basal side, transport is unidirectional.

• Secretion movement for EPI, NorEPI, vitamins, drugs (e.g. morphine, penicillin)

Secretion in Collecting Duct (CD)

Overall, allows removal of K+ from blood using Na+ in lumen of tubule. K+ secretion increased with Na+ in filtrate or total filtration flow since [K+] drops with increased flow (K+ is washed away).

Aldosterone increases Na+ and K+ channels on lumen side.

General Concepts and Renal Tubule Function

Acid-Base Homeostasis

If blood is too acidic or too basic, it causes denaturation in proteins and stops transporters, enzymes, channels, causing metabolism to fail.

Buffers of H+ in body with metabolism

Role of lungs for pH stability

Role of kidney for plasma pH and reabsorbing filtered H+.

Acids and Bases Summary

Usually body’s pH is around 7.4

pH and Homeostasis

Why does pH change throughout the day?

• Acid intake from diet

• Acid generation from metabolism (lactic acids and ketoacids)

• On average, body could have 1 mili Equivalents / kg of body weight per day. e.g. A 70 kg person has 70 mEq/day. Many important substances in the body are measured in equivalents. The technical definition of an equivalent is the amount of substance it takes to combine with 1 mole of hydrogen ions.

What does the body do to buffer pH?

• Use Hemoglobin (Hb)

• Use extracellular fluid bicarbonate

What are the mechanisms?

• Ventilation

• Kidney - Urine excretion of fixed acids/ammonia (bound H+ ions) that can’t be released via breathing. Takes couple hours for pH balance

• Plasma [H+] buffered

Important Terms

…-emia = in blood

…-osis = process

** Lung Versus Kidney

Chemistry and pH

PaCO2 = partial pressure of CO2 in blood

Reabsorption of Filtered HCO3- in PCT

Bicarbonate and H+ is in lumen / filtrate. It moves into the PCT cells as carbonic acid via water and CO2. Carbonic anhydrase allows separation again.

Intercalated Cells in DCT and CD Balance pH

Type A remedies acidosis

Type B remedies alkalosis

Intercalated A cell and A/B Functions on Side

• Notice the 2 ATPase involving H+ and K+

• K+ is leaked to blood. Can lead to hyperkalemia

Type B cell

• Is a mirror of the type A cell.

• HCO3- is secreted, transporters and ATPase are on basal side.

• Can cause hypokalemia.

Balance, Disturbances, and Analysis

Acid-base disturbances

Explain new bicarbonate ions are generated through ammonium ions and fixed acids

Classify four acid-base disorders

Acidosis

Mass Balance and pH

Kidney can adjust H+ and HCO3-

Kidney makes NH4+ and New Bicarbonate

Terms

• Proximal Convoluted Tubule (PCT)

• Glutamine = an amino acid in lumen on blood.

• Thick Ascending Loop of Henle (TAL)

Kidney Tubule actions

PCT cells can extract NH4+ from glutamine and new HCO3 is created.

NH4+ enters into the lumen from PCT cells.

• Kidney can bind free H+ and create bicarbonate.

• NH3 through blood is used by liver and converted to urea. Urea is pumped back into blood as Blood Urea Nitrogen (BUN). If kidneys have poor (sick) collecting ducts, the BUN is higher than normal.

Distal Convoluted Tubule (DCT) and Collecting Duct (CD) Excrete Fixed Acids and New HCO3-

DCT and CD can use carbonic anhydrase to produce bicarbonate and fixed acids (H2PO4) via H+/K+ ATPase.

Mass Balance for Net Acid Excretion

NAE = net acid excretion

Note actual output is very small (nano)

NAE = net acid excretion = [NH4] x Volume of urine (V) + [Titratable acid] x V - [HCO3-] x V

Usually [HCO3-] is negligible and can be assumed to be zero.

Acid-Base Disturbances

e.g. vomiting, loss of H+ protons, body becomes alkaline.

Respiratory vs. metabolic acidosis –> check PaCO2, it is higher than normal, it is respiratory.

• Regular PaCO2 = 40mmHg; regular [HCO3] = 24 mEq/ml

How to Analyze Acid-Base Disorders?

Ask these questions…

A mixed disorder is a combination of acidosis AND alkalosis causing a neutral pH, though it will not be addressed in this class (one example is someone breathing slowly (respiratory alkalosis) and vomiting (metabolic acidosis).

Metabolic disorder? - change ventilation

Respiratory disorder? - change [HCO3-] in kidney

Case Study

Note the lowered PaCO2 means the lung is already trying to compensate to remove CO2

[HCO3-] is lowered, implying diarrhea.