Urinary system & fluid

and acid-base

Mr JM Choshi
Office number 1043A, first floor, old Q-Block building
LEARNING OUTCOMES
Have an understanding of the following:
✓Functions of the kidneys
✓Anatomy of the urinary system
✓Overview of kidney function:
✓Filtration
✓Reabsorption
✓Secretion
✓Excretion
✓Micturition
 facts about YOUR
kidneys
✓ Bean-shaped, they receive about 20-25% of all blood pumped
by the heart
✓They filter about 8 litres of blood in an hour
✓Just one kidney donated is required to substitute two failed
kidneys
✓Kidneys will continue performing until they have lost 75-80%
of their function
FUNCTION OF THE KIDNEYS
• Most important function of the kidney is the homeostatic
regulation of water and ion content of the blood (salt and water
balance or fluid and electrolyte balance)

• Waste removal is important, however, disturbances in blood

volume or ion levels can cause serious medical problems before
accumulation of wastes reaches toxic levels
 Functions of the kidneys
1. Maintaining water balance in the body 7. Excreting many foreign compounds such as drugs, pesticides, food
additives etc
2. Maintaining proper osmolarity of body fluids, primarily through regulating 8. Producing erythropoietin, a hormone that stimulates red blood cell
water balance production
3. Regulating the quantity and concentration of most ECF ions including Na+, 9. Producing renin, an enzymatic hormone that triggers chain reaction
Cl-, K+, Ca2+etc important in salt conservation by the kidneys
4. Maintaining proper plasma volume, important in the long-term regulation 10. Converting vitamin D into its active form
of blood pressure. This function is accomplished through the kidney’s
regulatory role in salt (Na+ and Cl-) and water balance
5. Helping maintain the proper acid-base balance of the body by adjusting
urinary output of H+ and bicarbonate ions
6. Excreting metabolic waste products such as urea, uric acid and creatinine
 Anatomy of the urinary system
The urinary system consists of kidneys, ureters, bladder and urethra
The urinary system
• The pathway of water on its way from plasma to excretion in the urine
• Urine production begins when water and solutes move from plasma into hollow
tubules (nephrons) that make up the bulk of the paired kidneys
• The tubules modifies the composition of the fluid as it passes through
• The modified fluid, now called urine, leaves the kidney and passes into a hollow
tube called ureter
• Ureter leads to the urinary bladder, which temporarily stores urine
• The bladder expands and expel urine through a single tubule called urethra, a
process called urination or micturition
 The urethra in males exits the body through the shaft of the penis. In
females, the urethra opening is found anterior to the openings of the
vagina and anus

Urinary tract
The urethra in females has a shorter length and close proximity to
bacteria leaving large intestines, making them more prone to develop
bacterial infections of the bladder and kidneys, or urinary tract
infections (UTIs)

infections Most common cause of UTIs-bacterium E.coli-normally found in the

(UTIs)
large intestines, E.coli is pathogenic if it gets into the urethra

Most common symptoms of a UTI are pain or burning during urination

and increased frequency of urination. A urine sample of a patient with
UTI often contains many red and white blood cells, neither of which is
commonly found in normal urine. UTIs are treated with antibiotics
The kidneys
• The site of urine formation

• Lie on either side of the spine, outside the abdominal cavity, sandwiched
between membranous peritoneum, which lines the abdomen, and the bones and
muscles of the back
• Renal arteries supply blood to the kidneys
• Renal veins carry blood from the kidneys to the inferior vena cava
• Receive 20-25% of the cardiac output, constitute 0.4% of total body weight
The Nephron is the functional unit of the kidneys
• The interior of the kidney is arranged into two layers: An outer cortex and
inner medulla
• An organized arrangement of microscopic tubules called nephrons forms
the layers
• Nephron-functional unit of the kidney
• About 1 million nephrons in each kidney
• Approximately 80% of nephrons in each kidneys are contained within the
cortex (cortical nephrons) and the other 20% called juxtamedullary
nephrons dip down into the medulla
Structure of the kidney: Cross-sectional view
The nephron
• One nephron has two
arterioles and two sets
of capillaries that form a
portal system
Vascular elements of the kidney
• Blood enters the kidney via the renal artery then flows into smaller arterioles in the
cortex. The arrangement of blood vessels forms a portal system
• The renal portal system systems consists afferent arterioles, glomerulus, efferent
arterioles, peritubular capillaries
• In the juxtaglomerular nephrons, the long peritubular capillaries that dip into the
medulla are called the vasa recta
• Finally, the peritubular capillaries converge to form venules, sending blood out of the
kidney through the renal vein
• The function of renal portal system is to filter fluid out of the blood and into lumen of the
nephron at the glomerular capillaries, then to absorb fluid from the tubule lumen back
into the blood at the peritubular capillaries
Vascular elements of the kidney
• The renal portal system. Pathway of blood flow

Afferent arteriole Glomerulus Efferent arteriole

Venules and small

Peritubular capillaries
veins
TUBULAR ELEMENTS OF THE KIDNEY
• Basically the nephron
• The kidney tubule consists of a single layer of epithelia cells connected
together near their apical surface. The apical surfaces are folded into
microvilli
• The nephron begins with Bowman’s capsule that surrounds the
glomerulus. The endothelium of the glomerulus is fused to the epithelium
of Bowman’s capsule so that fluid filtering out of the capillaries passes
directly into the lumen of the tubule
• The combination of glomerulus and Bowman’s capsule is called the renal
corpuscle
Tubular elements of the kidney
• From Bowman’s capsule, filtered fluid flows into the proximal tubule, then
into the loop of Henle, a hairpin-shaped segment that dips down toward
the medulla and then back up.
• The loop of Henle is divided into two limbs, a descending limb and an
ascending limb
• The fluid then passes into the distal tubule
• The distal tubules drain into a single large tube called the collecting duct
• Collecting ducts passes from the cortex through the medulla and drain into
the renal pelvis
Vascular and
tubular
elements of the
kidney
Juxtaglomerular
apparatus
• The nephron twists and folds back
on itself so that the final part of the
ascending limb of the loop of Henle
passes between the afferent and
efferent arterioles.
• This region is known as the
juxtaglomerular apparatus
• The proximity of the ascending
limb and the arterioles allows
paracrine communication between
the two structures, a key feature of
kidney autoregulation
OVERVIEW OF KIDNEY FUNCTION
• The kidneys filter, reabsorb and secrete
• Three basic processes in the nephron
1. Filtration: is the movement of fluid from blood into the lumen of the nephron.
Filtration takes place only in the renal corpuscle, where walls of the glomerular
capillaries and Bowman’s capsule are modified to allow bulk flow of fluid. Filtered
fluid is called filtrate
2. Reabsorption: the process of moving substances in the filtrate from the tubular lumen
back into the peritubular capillaries
3. Secretion: selectively removes molecules from the blood and adds them to the filtrate
in the lumen. Unlike glomerular filtration, secretion is a more selective process that
usually uses membrane proteins to move molecules across the tubule epithelium
SEGMENTS OF NEPHRON AND THEIR FUNCTIONS
Segment of the nephron Processes
Renal corpuscle (glomerulus + Filtration of mostly protein-free plasma from the capillaries into the capsule
Bowman’s capsule)

Proximal tubule Isosmotic reabsorption of organic nutrients, ions, and water. Secretion of metabolites
and xenobiotics such as penicillin
Loop of Henle Reabsorption of ions in excess of water to create dilute fluid in the lumen

Distal nephron (distal tubule + Regulated reabsorption of ions and water for salt and water balance and pH
collecting duct) homeostasis
FILTRATION
• The first step in urine formation
• Filtration takes place in the renal corpuscle which consists of glomerular capillaries surrounded by
Bowman’s capsule
• Substances leaving the plasma must pass through three filtration barriers before entering the
tubule lumen
1. The glomerular capillary endothelium: the glomerular capillaries are fenestrated capillaries
with large pores that allow most components of the plasma to filter through the endothelium.
However, the pores are small enough to prevent blood cells from leaving the capillary. The
pores have negatively charged proteins that repel negatively charged plasma proteins
2. The Basal lamina: an acellular layer that separates the capillary endothelium from the
epithelium of Bowman’s capsule. It consists of negatively charged glycoproteins, collagen and
other proteins. The lamina acts as like a coarse sieve, excluding most plasma proteins from the
fluid that filter through it.
3. The epithelium of Bowman’s capsule, consists of specialised cells called podocytes
Self study
• Diabetic nephropathy
The filtration fraction
Capillary pressure causes filtration
• What drives filtration across the walls of the glomerular capillaries?
• Three pressures influence the glomerular filtration
1. Capillary blood pressure/hydrostatic pressure of blood flowing through the
glomerular capillaries forces fluid through the endothelium. Capillary blood
pressure averages 55 mmHg and favours filtration. Although blood pressure
decreases as blood moves through the capillaries, it remains higher than the
opposing pressures.
2. Capillary colloid osmotic pressure inside glomerular capillaries is higher than
that of fluid in Bowman’s capsule. This pressure gradient is due to the presence
of proteins in the plasma. The pressure gradient averages 30 mmHg and
favours fluid movement back into the capillaries.
Continued….
3. Capsule fluid pressure/hydrostatic fluid pressure is created by the
presence of fluid in the capsule that opposes fluid movement into the
capsule. Hydrostatic fluid pressure averages 15 mmHg, opposing filtration

• The volume of fluid that filters into Bowman’s capsule per unit time is the
glomerular filtration rate (GFR). Average GFR is 125 mL/min or 180 L/day.
Two factors influence GFR: net filtration pressure and filtration coefficient
• Filtration determined primarily by renal blood flow and blood pressure
• Filtration coefficient has two components; the surface area of the
glomerular capillaries available for filtration and the permeability of
interface between the capillary and Bowman’s capsule
Gfr is subject to autoregulation (Control of gfr)
• Autoregulation of GFR is a local process in which the kidney maintains a relatively
constant GFR in the face of normal fluctuations in blood pressure
• The function of autoregulation is to protect the barriers of filtration from high
blood pressures that might damage them
• Two mechanisms of autoregulation include myogenic response and
tubuloglomerular feedback
• The myogenic response is the intrinsic ability of vascular smooth muscle to
respond to changes in blood pressure
• The tubuloglomerular feedback is a paracrine signalling mechanism through
which changes in fluid flow through the loop of Henle influence GFR (local control
pathway)
MYOGENIC RESPONSE
Increase in blood pressure causes smooth muscles of the arterioles to
stretch

Stretch-sensitive ion channels and muscle cells depolarize

Depolarization opens voltage-gated Ca2+ channels, and the vascular

smooth muscle contracts
Vasoconstriction increases resistance to flow, and so blood flow
through the arteriole diminishes
The decrease in blood flow decreases filtration pressure in the
glomerulus
If blood pressure decreases, the tonic level of arteriolar contraction disappears and
the arteriole becomes dilated. Consequently, when mean blood pressure drops
below 80 mmHg GFR decreases
Tubuloglomerular feedback
• Is a local control pathway in which fluid flow through the tubule influences
GFR
• Is part of the juxtaglomerular apparatus
• The juxtaglomerular apparatus consists of macula densa and granular cells.
Paracrine signalling between the nephron and the afferent arteriole
influences GFR
• The modified portion of the tubule epithelium is a plaque of cells called the
macula densa
• The adjacent wall of the afferent arteriole has specialized smooth muscle
cells called granular cells (AKA juxtaglomerular cells)
Tubuloglomerular feedback
• The granular cells secrete renin, an enzyme involved in salt and water
balance.
• When NaCl delivery past the macula sensa increases as a result of
increased GFR, the macula densa cells send a paracrine message to
the neighbouring afferent arteriole. The afferent arteriole constricts,
increasing resistance and decreasing GFR
Juxtaglomerular
apparatus
• Consists of macula
densa and granular
cells. Paracrine
signalling between the
nephron and afferent
arteriole influences GFR
Tubuloglomerular feedback
REABSORPTION
• Reabsorption may be active or passive
• Reabsorption of water and solutes from the tubule lumen to the
extracellular fluid depends on active transport
• The filtrate flowing out of the Bowman’s capsule into the proximal
tubule has the same solute concentrations as extracellular fluid
• To move solute of the lumen, the tubule cells must therefore use
active transport to create concentration or electrochemical gradients
• Water osmotically follows solutes as they are reabsorbed
OVERVIEW OF REABSORPTION
SECRETION
• Secretion is the transfer of molecules from extracellular fluid into the lumen of the nephron
• Secretion, like reabsorption, depends mostly on membrane transport systems
• The secretion of K+ and H+ ions by the distal nephron is important in the homeostatic regulation
of those ions
• Organic compounds including metabolites produced in the body such as creatinine or urea and
xenobiotics (substances brought into the body) such as drugs (antiretroviral drugs)
• Secretion enables the nephron to enhance excretion of a substance
• Secretion is an active process because it requires moving substances against their concentration
gradients
• Transporters, for example, organic anion transporters (OAT) family, are responsible to organic
solute excretion
EXCRETION
• Urine output is the result of all processes that take place in the kidney
• Glucose, amino acids, and useful metabolites have been reabsorbed back
into the blood while organic wastes are more concentrated in the urine
• The concentrations of ions and water in the urine are highly variable,
depending on the state of the body
• The excretion rate of a substance depends on (1) the filtration rate of that
substance and (2) whether the substance is reabsorbed, secreted or both
• Renal handling of a substance and GFR are aften used in clinical practice.
For example, clinicians use a person’s GFR as an indicator of overall kidney
function
EXCRETION
• Clearance is a non-invasive way to measure GFR
• Clearance of a solute is the rate at which that solute disappears from
the body by excretion or by metabolism
• In clinical settings, physicians use creatinine to estimate GFR. Creatine
is a breakdown product of phosphocreatine, an energy-storage
compound found primarily in muscles.
• Creatinine clearance is routinely used to estimate GFR
• Inulin clearance directly measures GFR. Not used in clinical practice
because it is expensive, requires intravenous injection of inulin
Micturition
• Once filtrate leaves the collecting duct, it can no longer be modified,
and its composition does not change
• The filtrate, now called urine, flows into the renal pelvis and then
down the ureter to the bladder
• In the bladder, the urine is temporarily stored until released by a
process known as urination or micturition
• Micturition is a spinal reflex that is subject to both conscious and
unconscious control from higher brain centers
MICTURITION