OPTOMETRY · SEMESTER 1
Renal Physiology
Human Anatomy and Physiology
RENAL PHYSIOLOGY
INTRODUCTION
- The urinary system is the main excretory system and consists of the following structures:
- 2 kidneys, which secrete urine
- 2 ureters, which convey the urine from the kidneys to the urinary bladder
- the urinary bladder where urine collects and is temporarily stored
the urethra through which the urine passes from the urinary bladder to the exterior.
Renal Physiology
Urine is excreted from each kidney through its ureter and is stored in the urinary bladder until it is expelled from the body through the urethra.
The specialized branch of medicine that deals with structure, function, and diseases of the male and female urinary systems and the male reproductive system is known as nephrology. The branch of surgery related to male and female urinary systems and the male reproductive system is called urology.
INTRODUCTION CONT…
INTRODUCTION CONT…
The urinary system plays a vital part in maintaining homeostasis of water and electrolyte concentrations within the body.
- The kidneys produce urine that contains metabolic waste products,
including the nitrogenous compounds urea and uric acid, excess ions and some drugs.
FUNCTIONS OF URINARY SYSTEM
- The main functions of the urinary system and its components are to
- Regulate blood volume and composition (e.g. sodium, potassium and calcium)
- Regulate blood pressure.
- Regulate pH homeostasis of the blood.
- Contributes to the production of red blood cells by the kidney.
Helps synthesize calcitrol the (active form of Vitamin D).
Stores waste product (mainly urea and uric acid) before it and other products are removed from the body.
functions CONT …
The main functions of the kidneys are:
Formation and secretion of urine, which regulates total body water, electrolyte and acid–base balance and enables excretion of waste products Production and secretion of erythropoietin, the hormone that stimulates formation of red blood cells Production and secretion of renin, an important enzyme in the control of blood pressure
Kidneys
The kidneys lie on the posterior abdominal wall, one on each side of the vertebral column, behind the peritoneum and below the diaphragm.
They extend from the level of the 12th thoracic vertebra to the 3rd lumbar vertebra, receiving some protection from the lower rib cage, specifically11th & 12th ribs .
The right kidney is usually slightly lower than the left, probably because of the considerable space occupied by the liver.
External Anatomy of the Kidney
Near the center of the concave medial border of the kidney is a vertical fissure called the hilus, through which the ureter leaves and blood vessels, lymphatic vessels, and nerves enter and exit.
Three layers of tissue surround each kidney: the innermost renal capsule, the adipose capsule, and the outer renal fascia.
Nephroptosis is an inferior displacement of the kidneys. It most often occurs in thin people. This condition is dangerous because the ureters may kink and block urine flow.
Internal Anatomy of the Kidney
Internally, the kidneys consist of cortex, medulla, pyramids, papillae, columns, calyces, and pelves.
The renal cortex and renal pyramids constitute the functional portion or parenchyma of the kidney.
The nephron is the functional unit of the kidney.
Internal Anatomy of the Kidney CONT …
- Parenchyma of kidney
- renal cortex = superficial layer of kidney
- renal medulla
- inner portion consisting of 8-18 cone-shaped renal pyramids separated by renal columns
- renal papilla point toward center of kidney
- Drainage system fills renal sinus cavity
- cuplike structure (minor calyces) collect urine from the papillary ducts of the papilla
minor & major calyces empty into the renal pelvis which empties into the ureter
Internal Anatomy of the Kidney CONT …
Blood Supply of the Kidneys
Blood enters the kidney through the renal artery and exits via the renal vein.
Kidneys CONT …
- Kidneys are bean-shaped organs, about 11 cm long, 6 cm wide, 3 cm thick and weigh 150 g.
They are embedded in, and held in position by, a mass of fat.
A sheath of fibrous connective tissue, also known as the renal fascia, encloses the kidney and the renal fat.
The kidneys receive about 20% of the cardiac output.
The nephron
The nephron consists of a tubule closed at one end, the other end opening into a collecting tubule.
The closed or blind end is indented to form the cup-shaped glomerular capsule (Bowman’s capsule), which almost completely encloses a network of tiny arterial capillaries, the glomerulus.
The nephron CONT …
The loop of Henle consists of a descending limb, a thin ascending limb, and a thick ascending limb.
There are two types of nephrons that have differing structure and function.
A cortical nephron usually has its glomerulus in the outer portion of the cortex and a short loop of Henle that penetrates only into the outer region of the medulla.
A juxtamedullary nephron usually has its glomerulus deep in the cortex close to the medulla; its long loop of Henle stretches through the medulla and almost reaches the renal papilla.
Cortical Nephron
- 80-85% of nephrons are cortical nephrons
Renal corpuscles are in outer cortex and loops of Henle lie mainly in cortex
Juxtamedullary Nephron
15-20% of nephrons are juxtamedullary nephrons Renal corpuscles close to medulla and long loops of Henle extend into deepest medulla enabling excretion of dilute or concentrated urine
The nephron CONT …
After entering the kidney at the hilum the renal artery divides into smaller arteries and arterioles.
In the cortex an arteriole, the afferent arteriole, enters each glomerular capsule and then subdivides into a cluster of tiny arterial capillaries, forming the glomerulus.
The nephron CONT …
Between these capillary loops are connective tissue phagocytic mesangial cells, which are part of the monocyte–macrophage system The blood vessel leading away from the glomerulus is the efferent arteriole.
The afferent arteriole has a larger diameter than the efferent arteriole, which increases pressure inside the glomerulus and drives filtration across the glomerular capillary walls
The nephron CONT …
Juxtaglomerular Apparatus
The juxtaglomerular apparatus (JGA) is a specialized structure located in the kidney, specifically at the junction of the afferent arterioles and the glomerulus.
It plays a crucial role in regulating renal blood flow, glomerular filtration rate (GFR), and systemic blood pressure.
- The JGA consists of three main types of cells:
Macula Densa
Juxtaglomerular Cells
Extraglomerular Mesangial Cells
Juxtaglomerular Apparatus CONT …
Macula Densa: This is a group of specialized epithelial cells located in the distal convoluted tubule. The macula densa senses sodium chloride (NaCl) concentrations in the tubular fluid. When NaCl levels are high, it signals for constriction of the afferent arteriole, which decreases GFR. Conversely, when NaCl levels are low, it promotes vasodilation of the afferent arteriole and stimulates renin release.
Juxtaglomerular Cells: Also known as granular cells, these modified smooth muscle cells are primarily located in the tunica media of the afferent arterioles. They secrete renin in response to several stimuli:
- Stimulation via beta-1 adrenergic receptors.
- A decrease in renal perfusion pressure detected directly by these cells.
A decrease in NaCl concentration sensed by the macula densa.
Juxtaglomerular Apparatus CONT …
Extraglomerular Mesangial Cells: These cells are situated between the afferent and efferent arterioles and have contractile properties similar to vascular smooth muscle. They assist in regulating GFR by altering vessel diameter and also contain renin.
Juxtaglomerular Apparatus CONT …
- Structure where afferent arteriole makes contact with ascending limb of loop of Henle
- macula densa is thickened part of ascending limb
juxtaglomerular cells are modified muscle cells in arteriole
PART II
Formation of urine
The kidneys form urine, which passes through the ureters to the bladder for storage prior to excretion.
The composition of urine reflects exchange of substances between the nephron and the blood in the renal capillaries.
Waste products of protein metabolism are excreted, electrolyte levels are controlled and pH (acid–base balance) is maintained by excretion of hydrogen ions.
Formation of urine CONT …
- There are three processes involved in the formation of urine:
- Filtration
- Selective reabsorption
Secretion.
Filtration
This takes place through the semipermeable walls of the glomerulus and glomerular capsule.
Water and other small molecules pass through, although some are reabsorbed later.
Blood cells, plasma proteins and other large molecules are too large to filter through and therefore remain in the capillaries.
The filtrate in the glomerulus is very similar in composition to plasma with the important exceptions of plasma proteins and blood cells.
Filtration
The volume of filtrate formed by both kidneys each minute is called the glomerular filtration rate (GFR).
In a healthy adult the GFR is about 125 ml/min, i.e. 180 litres of filtrate are formed each day by the two kidneys.
Nearly all of the filtrate is later reabsorbed from the kidney tubules with less than 1%, i.e. 1 to 1.5 litres, excreted as urine.
The differences in volume and concentration are due to selective reabsorption of some filtrate constituents and tubular secretion of others.
Filtration AND FILTRATION PRESSURES
Filtration takes place because there is a difference between the blood pressure in the glomerulus and the pressure of the filtrate in the glomerular capsule.
Because the efferent arteriole is narrower than the afferent arteriole, a capillary hydrostatic pressure of about 7.3 kPa (55 mmHg) builds up in the glomerulus.
This pressure is opposed by the osmotic pressure of the blood, provided mainly by plasma proteins, about 4 kPa (30 mmHg), and by filtrate hydrostatic pressure of about 2 kPa (15mmHg) in the glomerular capsule.
Filtration AND FILTRATION PRESSURES
Blood constituents in glomerular filtrate
- Water
- Mineral salts
- Amino acids
Ketoacids Glucose
- Some hormones
- Creatinine
- Urea
- Uric acid
Some drugs (small molecules)
Blood constituents remaining in glomerular capillaries
- Leukocytes
- Erythrocytes
- Platelets
- Plasma proteins
Some drugs (large molecules)
Selective reabsorption
Most reabsorption from the filtrate back into the blood takes place in the proximal convoluted tubule, whose walls are lined with microvilli to increase surface area for absorption.
Materials essential to the body are reabsorbed here, including some water, electrolytes and organic nutrients such as glucose. Some reabsorption is passive, but some substances are transported actively.
Only 60–70% of filtrate reaches the loop of the nephron.
Selective reabsorption CONT …
Much of this, especially water, sodium and chloride, is reabsorbed in the loop, so only 15–20% of the original filtrate reaches the distal convoluted tubule, and the composition of the filtrate is now very different from its starting values.
More electrolytes are reabsorbed here, especially sodium, so the filtrate entering the collecting ducts is actually quite dilute. The main function of the collecting ducts therefore is to reabsorb as much water as the body needs.
Selective reabsorption CONT …
Active transport takes place at carrier sites in the epithelial membrane, using chemical energy to transport substances against their concentration gradients.
Some ions, e.g. sodium and chloride, can be absorbed by both active and passive mechanisms depending on the site in the nephron.
Some constituents of glomerular filtrate (e.g. glucose, amino acids) do not normally appear in urine because they are completely reabsorbed unless blood levels are excessive.
Reabsorption of nitrogenous waste products, such as urea, uric acid and creatinine is very limited.
Hormones that influence selective reabsorption
Parathyroid hormone
This comes from the parathyroid glands and together with calcitonin from the thyroid gland regulates the reabsorption of calcium and phosphate from the distal collecting tubules.
Antidiuretic hormone
Also known as ADH, this is secreted by the posterior lobe of the pituitary gland and increases the permeability of the distal convoluted tubules and collecting tubules, increasing water reabsorption.
Secretion of ADH is controlled by a negative feedback system
Antidiuretic hormone MECHANISM
Hormones that influence selective reabsorption CONT …
Aldosterone
Secreted by the adrenal cortex, this hormone increases the reabsorption of sodium and water, and the excretion of potassium. Secretion is regulated through a negative feedback system
Aldosterone
Atrial natriuretic peptide
Also known as ANP, this hormone is secreted by the atria of the heart in response to stretching of the atrial wall. It decreases reabsorption of sodium and water from the proximal convoluted tubules and collecting ducts. Secretion of ANP is also regulated by a negative feedback system
Atrial natriuretic
Tubular secretion
Filtration occurs as the blood flows through the glomerulus. Substances not required and foreign materials, e.g. drugs including penicillin and aspirin, may not be cleared from the blood by filtration because of the short time it remains in the glomerulus.
Such substances are cleared by secretion from the peritubular capillaries into the convoluted tubules and excreted from the body in the urine.
Tubular secretion of hydrogen ions (H+) is important in maintaining normal blood pH.
Renin–angiotensin–aldosterone system
Sodium is a normal constituent of urine and the amount excreted is regulated by the hormone aldosterone, secreted by the adrenal cortex.
Cells in the afferent arteriole of the nephron release the enzyme renin in response to sympathetic stimulation, low blood volume or by low arterial blood pressure.
Renin converts the plasma protein angiotensinogen, produced by the liver, to angiotensin 1.
Renin–angiotensin–aldosterone system CONT …
Angiotensin converting enzyme (ACE), formed in small quantities in the lungs, proximal convoluted tubules and other tissues, converts angiotensin 1 into angiotensin 2, which is a very potent vasoconstrictor and increases blood pressure.
Renin and raised blood potassium levels also stimulate the adrenal gland to secrete aldosterone.
Renin–angiotensin–aldosterone system CONT …
Water is reabsorbed with sodium and together they increase the blood volume, leading to reduced renin secretion through the negative feedback mechanism.
When sodium reabsorption is increased potassium excretion is increased, indirectly reducing intracellular potassium.
Micturition IN INFANTS
When 300 to 400 ml of urine have accumulated in the bladder, afferent autonomic nerve fibres in the bladder wall sensitive to stretch are stimulated.
In the infant this initiates a spinal reflex and micturition occurs.
Urine passed in the response to parasympathetic stimulation of the bladder, causing contraction of the detrusor muscle and relaxation of the internal urethral sphincter.
Urine is expelled from the bladder and passes through the urethra before leaving the body.
Micturition IN INFANTS CONT …
When the nervous system is fully developed, the micturition reflex is stimulated but sensory impulses also pass upwards to the brain and there is awareness of the need to pass urine.
By learned and conscious effort, contraction of the external urethral sphincter and muscles of the pelvic floor can inhibit micturition until it is convenient to empty the bladder It should be understood that infants can not control their external urethral sphincter, but it should not be confused with bed wetting(nocturnal enuresis) in older children and adults since it has several causes, but in infants may not have fully developed bladder control by the age of 4 to 6 years.
Micturition IN ADULTS
In adults, urine is passed when the detrusor muscle contracts, and there is reflex relaxation of the internal sphincter and voluntary relaxation of the external sphincter.
It can be assisted by increasing the pressure within the pelvic cavity, achieved by lowering the diaphragm and contracting the abdominal muscles (Valsalva’s manoeuvre).
Micturition IN ADULTS CONT …
Overdistension of the bladder is extremely painful, and when this stage is reached there is a tendency for involuntary relaxation of the external sphincter to occur allowing a small amount of urine to escape, provided there is no mechanical obstruction.
Involuntary loss of urine is known as incontinence.
Extracellular Fluid Osmolarity
Osmolarity is a measure of the concentration of solutes in a solution, and it plays a crucial role in maintaining fluid balance within the body.
In the context of extracellular fluid (ECF), osmolarity refers to the concentration of solutes present in the fluid outside of cells, which includes interstitial fluid and plasma.
The normal osmolarity range for extracellular fluid is typically between 280 to 295 mOsm/kg. This range indicates that the ECF has a balanced concentration of solutes, which is essential for proper cellular function and overall homeostasis.
Extracellular Fluid Osmolarity CONT …
Monitoring extracellular fluid osmolarity is vital for diagnosing various medical conditions.
For instance, deviations from the normal range can indicate issues such as dehydration, overhydration, or disorders affecting kidney function.
An increased osmolality may suggest dehydration or conditions like hypernatremia, while decreased osmolality could indicate overhydration or hyponatremia.
Components Affecting Extracellular Fluid Osmolarity
The primary contributors to extracellular osmolarity are electrolytes, particularly sodium (Na+), chloride (Cl-), and bicarbonate (HCO3-).
Sodium is the major determinant of plasma osmolality, as it is predominantly found in the extracellular compartment.
Other substances such as glucose and urea also contribute to osmolarity but to a lesser extent.
Sodium and potassium balance
Sodium is the most common cation (positively charged ion) in extracellular fluid and potassium is the most common intracellular cation.
Sodium is a constituent of almost all foods and salt is often added to food during cooking.
- This means that intake is usually in excess of the body’s needs.
It is excreted mainly in urine and sweat.
The amount of sodium excreted in sweat is insignificant except when sweating is excessive.
Sodium and potassium balance cont …
This may occur when there is pyrexia (fever), a high environmental temperature or during sustained physical exercise.
Normally the renal mechanism described below maintains the concentration of sodium and potassium within physiological limits.
When excessive sweating is sustained, e.g. living in a hot climate or working in a hot environment, acclimatisation occurs in about 7 to 10 days and the amount of electrolytes lost in sweat is reduced.
Sodium and potassium balance cont …
Sodium and potassium occur in high concentrations in digestive juices – sodium in gastric juice and potassium in pancreatic and intestinal juice.
Normally these ions are reabsorbed by the colon, but following acute and prolonged diarrhoea they may be excreted in large quantities with resultant electrolyte imbalance.