HUMAN PHYSIOLOGY (normal) 2020 LSUPhC,

HUMAN PHYSIOLOGY (normal)

LECTURE 16. The Physiology of Kidneys. Excretion Lyubomyr Vovkanych Department of Anatomy & Physiology LSUPhC

L.S.Vovkanych, LSUPhC, 2020

Excretion Process by which the unwanted substances and metabolic wastes are eliminated from the body

Various systems/organs in the body are involved in excretion:

• Digestive system excretes food residues in the form of feces

• Lungs remove carbon dioxide

• Skin excretes water, salts and some wastes

• Liver excretes many substances like bile pigments, heavy metals, drugs, toxins, bacteria, etc.

The renal system or urinary system has maximum excretory capacity L.S.Vovkanych, LSUPhC, 2020

Functions of Kidney • Excretion of Waste Products (urea, uric acid, creatinine,

bilirubin, toxins, drugs, heavy metals pesticides, etc.) • Maintenance of

• Water Balance • Electrolyte Balance (sodium, potassium etc.) • Acid–Base Balance (kidneys play major role in preventing

acidosis) • Hemopoietic Function (erythropoietin and thrombopoietin) • Endocrine Function (renin, calcitriol etc.) • Regulation of Blood Pressure (regulating the volume of

extracellular fluid and renin-angiotensin mechanism) L.S.Vovkanych, LSUPhC, 2020

Nephron Structural and functional unit of the kidney Each nephron is formed by two parts • Renal (Malpighian) corpuscle:

• Glomerulus (capillaries with fenestrated wall)

• Bowman (glomerular) capsule (formed by two layers)

• Renal tubule • Proximal convoluted tubule • Nephron loop (Loop of Henle)

• Descending limb (thick and thin)

• Hairpin bend • Ascending limb (thin and thick)

• Distal convoluted tubule L.S.Vovkanych, LSUPhC, 2020

Types of Nephrons Cortical Nephrons • Located mostly within

superficial cortex of kidney

• Nephron loop is relatively short

• Efferent arteriole delivers blood to a network of peritubular capillaries

Juxtamedullary Nephrons • Nephron loops extend

deep into medulla • Peritubular capillaries

connect to vasa recta L.S.Vovkanych, LSUPhC, 2020

Juxtaglomerular Apparatus • Is a specialized organ situated

near the glomerulus of each nephron, is formed by three different structures:

• Macula densa • Extraglomerular mesangial cells

(Lacis cells) • Juxtaglomerular cells (granular

cells) - specialized smooth muscle cells


Renal Blood Flow • Renal arteries arise directly from the aorta, receives about

25% of cardiac output • Renal circulation has a portal system (double network of

capillaries) - the glomerular capillaries and peritubular capillaries

• Renal glomerular capillaries form high pressure bed with a pressure of 60 mm Hg to 70 mm Hg (in other regions - 25 mm Hg), which is important for filtration

• High pressure is maintained in the glomerular capillaries because the diameter of afferent arteriole is more than that of efferent arteriole

• Peritubular capillaries form a low pressure bed with a pressure of 8 mm Hg to 10 mm Hg, which is important for tubular reabsorption L.S.Vovkanych, LSUPhC, 2020

Regulation of Renal Blood Flow • Renal blood flow is

regulated mainly by autoregulation

• Blood flow to kidneys - normal with the mean arterial blood pressure 60-180 mm Hg

• Renal autoregulation is important to maintain the glomerular filtration rate (GFR)

• Two mechanisms of renal autoregulation: • Myogenic response • Tubuloglomerular feedback L.S.Vovkanych, LSUPhC, 2020

Regulation of Renal Blood Flow Myogenic Response • If the blood flow to kidneys increases, it stretches the wall of the

afferent arteriole • This leads to the contraction of smooth muscles in afferent

arteriole and its constriction (blood flow is decreased) Tubuloglomerular Feedback • When GFR increases macula densa releases adenosine • Adenosine causes constriction of afferent arteriole. • When GFR decreases macula densa secretes prostaglandin

(PGE2), bradykinin and renin • PGE 2 and bradykinin cause dilatation of afferent arteriole • Renin induces the formation of angiotensin II, which causes

constriction of efferent arteriole L.S.Vovkanych, LSUPhC, 2020

Renin-angiotensin System

ECF = Extracellular fluid, ACE = Angiotensin-converting enzyme, GFR = Glomerular filtration rate, ADH = Antidiuretic hormone, CRH = Corticotropin-releasing hormone, ACTH = Adrenocorticotropic hormone


Urine Formation The rates of substance excretion into the urine depends on three renal processes • glomerular filtration • reabsorption of substances

from the renal tubules into the blood

• secretion of substances from the blood into the renal tubules

Urinary excretion rate = Filtration rate - Reabsorption rate + Secretion rate L.S.Vovkanych, LSUPhC, 2020

Filtration, Reabsorption, and Excretion of Different Substances

Substance Filtered Reabsorbed Excreted % reabsorbed

Glucose (g/day) 180 180 0 100 Bicarbonate (mEq/day)

4,320 4,318 2 >99.9

Sodium (mEq/day) 25,560 25,410 150 99.4 Chloride (mEq/day)

19,440 19,260 180 99.1

Potassium (mEq/day)

756 664 92 87.8

Urea (g/day) 46.8 23.4 23.4 50 Creatinine (g/day) 1.8 0 1.8 0 L.S.Vovkanych, LSUPhC, 2020

Glomerular Filtration • Process by which the blood is filtered while passing through the

filtration membrane • Filtration membrane is formed by three layers:

• Glomerular capillary membrane (has many pores called fenestrae or filtration pores)

• Basement membrane • Visceral layer of Bowman capsule (single layer of flattened

epithelial cells - podocytes) • Plasma (without blood cells and proteins) is filtered into the

Bowman capsule, the filtered fluid is called glomerular filtrate • Glomerular filtration rate (GFR) - the total quantity of filtrate

formed in all the nephrons of both the kidneys in the given unit of time

• Normal GFR is 125 mL/minute or about 180 L/day (filtration fraction varies from 15% to 20%) L.S.Vovkanych, LSUPhC, 2020

Glomerular Filtration


Filterability of Substances by Glomerular Capillaries

Substance Molecular Weight

Filterability

Water 18 1.0 Sodium 23 1.0 Glucose 180 1.0 Inulin 5,500 1.0 Myoglobin 17,000 0.75 Albumin 69,000 0.005

Filterability of Solutes Is Inversely Related to Their Size L.S.Vovkanych, LSUPhC, 2020

Forces Causing Filtration

Net filtration pressure = GCP – (COP + BCP) = 20 mm Hg GCP - Glomerular capillary pressure COP - Colloidal Osmotic Pressure BCP - Bowman capsule pressure

Favors glomerular

filtration, varies between 45 and

70 mm Hg

Opposes glomerular

filtration

Opposes glomerular

filtration


Factors regulating GFR Is directly proportional to:

• renal blood flow

• glomerular capillary pressure

• permeability of glomerular capillary membrane

Is inversely proportional to:

• colloidal osmotic pressure

• hydrostatic pressure in the Bowman capsule

• The constriction of afferent arteriole reduces the GFR (reduces blood flow), constriction of efferent arteriole initially increase the GFR with next decrease (stagnation of blood in the capillaries)


Tubular Reabsorption Process by which water and other substances are transported from renal tubules back to the blood Reabsorption are of two types: • Active reabsorption

(sodium, calcium, potassium, phosphates, sulfates, bicarbonates, glucose, amino acids, ascorbic acid, etc.)

• Passive reabsorption (chloride, water, etc.) L.S.Vovkanych, LSUPhC, 2020

Active Transport (of Na+) • The sodium-potassium

pump transports sodium from the interior of the cell across the basolateral membrane, creating a low intracellular sodium concentration and a negative intracellular electrical potential.

• The low intracellular sodium concentration and the negative electrical potential cause sodium ions to diffuse from the tubular lumen into the cell through the brush border L.S.Vovkanych, LSUPhC, 2020

Secondary Active Transport • Co-transport of glucose

and amino acids along with sodium ions through the apical side of the tubular epithelial cells, followed by facilitated diffusion through the basolateral membranes

• Counter-transport of hydrogen ions from the interior of the cell across the apical membrane and into the tubular lumen L.S.Vovkanych, LSUPhC, 2020

Mechanism of Reabsorption • Glucose - completely reabsorbed in the proximal

convoluted tubule by secondary active transport (sodium cotransport) mechanism (sodium-dependant glucose cotransporter 2 (SGLT2) and glucose transporter 2 (GLUT2).

• Amino Acids - reabsorbed completely in proximal convoluted tubule by secondary active transport mechanism along with sodium

• Bicarbonates - reabsorbed actively, mostly in proximal tubule


Regulation of Tubular Reabsorption • The reabsorption increase when GFR increases,

sympathetic nervous is activating and under the hormonal influence

Aldosterone Increases sodium reabsorption in ascending limb, distal convoluted tubule and collecting duct

Angiotensin II Increases sodium reabsorption in proximal tubule, thick ascending limb, distal tubule and collecting duct

Antidiuretic hormone

Increases water reabsorption in distal convoluted tubule and collecting duct

Natriuretic factors

Decreases sodium reabsorption

Parathormone Increases reabsorption of calcium, magnesium and hydrogen

Calcitonin Decreases calcium reabsorption L.S.Vovkanych, LSUPhC, 2020

Threshold for Substances • High-threshold substances are completely reabsorbed from renal

tubules and do not appear in urine under normal conditions (glucose, amino acids etc)

• Low-threshold substances are the substances, which appear in urine even under normal conditions (urea, uric acid, phosphate, etc.)

• Non-threshold substances are not reabsorbed and are excreted in urine irrespective of their plasma level (creatinine etc.)

• Transport maximum (Tm) - a maximum rate at which substances could be reabsorbed

• Tm for glucose is 375 mg/minute in adult males, which determines the renal threshold

• Renal threshold is the plasma concentration at which a substance appears in urine. Renal threshold for glucose is 180 mg/dL L.S.Vovkanych, LSUPhC, 2020

Glucose Reabsorption • The renal threshold for

glucose is 180 mg/dL • Glucose is completely

reabsorbed from tubular fluid if its concentration in blood is below 180 mg/dL

• When the blood level of glucose reaches 180 mg/dL it is not reabsorbed completely; hence it appears in urine. L.S.Vovkanych, LSUPhC, 2020

Tubular Secretion • Process by which the substances are transported from blood

into renal tubules • Also called tubular excretion

• Ammonia is secreted in the proximal convoluted tubule • Potassium is secreted actively by sodium-potassium pump in

proximal and distal convoluted tubules and collecting ducts • Hydrogen ions are secreted in the proximal and distal

convoluted tubules • Urea is secreted in loop of Henle.


Proximal Convoluted Tubule Active reabsorption: glucose, amino acids, vitamins, ions Passive reabsorption: urea, chloride ions, lipid-soluble materials, water Secretion: Hydrogen ions, ammonium ions, creatinine, drugs, and toxins

Reabsorption 60-70% of the water, 99-100% of the organic substrates 60-70% of the Na+ and Cl-


Descending Loop of Henle

Highly permeable to water Reabsorption of 25% of the water (45 L/day).


Thick Ascending Loop of Henle Reabsorption 20-25% of the sodium and chloride ions (and other ions, such as calcium, bicarbonate, and magnesium); Active transport via Na+-K+ or Cl- transporter Osmosis Secretion of hydrogen ions

Impermeable to water, the concentration gradient in the medulla is created


Distal Convoluted Tubule (early segment)

Virtually impermeable to water and urea Reabsorption 5% of sodium chloride, chloride, calcium, and magnesium

of


Distal Convoluted Tubule and Collecting Tubule

Reabsorption of • water - ADH

stimulated • sodium ions -

aldosterone stimulated

• calcium ions - (hormone controlled)

Secretion: Hydrogen ions, ammonium ions, potassium ions, creatinine, drugs, toxins


Medullary Collecting Duct

Reabsorption of • water - ADH

stimulated • sodium ions -

aldosterone stimulated

• urea (distal portions only)

Secretion: Potassium and hydrogen ions (variable) L.S.Vovkanych, LSUPhC, 2020

Concentration or Dilution of Urine • Every day 180 L of

glomerular filtrate is formed with osmolarity the same as that of plasma and it is 300 mOsm/L

• Only 1,5-2 L of urine is formed, urine is concentrated and its osmolarity is four times more than that of plasma, i.e. 1,200 mOsm/L

• Dilution or concentration of urine depends upon water content of the body L.S.Vovkanych, LSUPhC, 2020

Formation of Dilute Urine • When water content in the body increases, kidney can

excrete as much as 20 L/day of dilute urine • This is achieved by inhibition of water reabsorption from

renal tubules by ADH • Obligatory Water Reabsorption

• Is water movement that cannot be prevented • Usually recovers 85% of filtrate produced

• Facultative Water Reabsorption (15% of filtrate volume ) • Controls volume of water reabsorbed along DCT and

collecting system • Is controlled by ADH L.S.Vovkanych, LSUPhC, 2020

Formation of Concentrated Urine • When the water content in body decreases, kidney retains water

and excretes concentrated urine • It involves two processes:

• Development and maintenance of medullary gradient by countercurrent system

• Secretion of ADH • Medullary gradient - the osmolarity increases from outer part

towards the inner part of medulla gradually and reaches the maximum near renal sinus (1,200 mOsm/L)

• Is developed by Countercurrent multiplier formed by loop of Henle

• Main reason for the hyperosmolarity of medullary is the active reabsorption of sodium chloride and other solutes from ascending limb of Henle L.S.Vovkanych, LSUPhC, 2020

Countercurrent multiplier system

Numerical values are in milliosmoles per liter L.S.Vovkanych, LSUPhC, 2020

Formation of a concentrated urine • If ADH levels are

high • cortical collecting

tubule and collecting ducts becomes highly permeable to water

• large amounts of water are reabsorbed into the cortex

• at the end of the collecting ducts the osmolarity is 1200 mOsm/L L.S.Vovkanych, LSUPhC, 2020

Changes in Osmolarity in Tubular Segments

Numerical values indicate the approximate volumes in milliliters per minute or in osmolarities in milliosmoles per liter of fluid


Nerve Supply to Urinary Bladder and Sphincters Sympathetic

Parasympathetic

Somatic

Sympathetic (hypogastric) nerve causes relaxation of detrusor muscle and constriction of the internal sphincter Parasympathetic (pelvic) nerve causes contraction of detrusor muscle and relaxation of the internal sphincter Pudendal nerve maintains the tonic contraction of the skeletal muscle fibers of the external sphincter


Micturition Reflex and Urination • The bladder fills with urine • Stretch receptors in urinary bladder stimulate sensory fibers in

pelvic nerve • Stimulus travels from afferent fibers in pelvic nerves to sacral

spinal cord • Parasympathetic efferent fibers in pelvic nerves stimulate

ganglionic neurons in wall of bladder • Postganglionic neuron in intramural ganglion stimulates

detrusor muscle contraction • Strong micturition reflex causes depression of the tonic activation

of external sphincter by pudendal nerves • Urination will occur Reflex is controlled by strong facilitative and inhibitory centers in the brain stem (mainly in the pons) and cerebral cortex L.S.Vovkanych, LSUPhC, 2020

References Martini R., Nath J. Fundamentals of Anatomy & Physiology. Eighth Edition

Guyton, Arthur C. Textbook of medical physiology / Arthur C. Guyton, John E. Hall. - 11th ed.

Sembulingam K., Sembulingam P. Essentials of Medical Physiology. Sixth Edition

Scanlon, Valerie C. Essentials of anatomy and physiology / Valerie C. Scanlon, Tina Sanders. — 5th ed.

Fox: Human Physiology. Eighth Edition

Silbernagl S., Despopoulos A. Color Atlas of Physiology. 6th edition


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HUMAN PHYSIOLOGY (normal) 2020 LSUPhC,