BODY FLUIDS

Body fluids are distributed between

the intracellular fluid (ICF) and
extracellular fluid (ECF)
compartments.
The ICF compartment consists of
fluid contained within all of the
billions of cells in the body. It is the
larger of the two compartments,
with approximately two thirds of
the body water in healthy adults.
The remaining one third of body
water is in the ECF compartment,
which contains all the fluids outside
the cells, including those in the
interstitial or tissue spaces and
blood vessels.
 BODY FLUIDS

CATIONS ANIONS

CHLORIDE
ECF SODIUM
BICARBONATE

POTASSIUM PROTEINS
ICF
MAGNESIUM PHOSPHORUS
 DIFFUSION AND OSMOSIS
Diffusion is the movement of charged or
uncharged particles along a concentration
gradient.
Osmosis is the movement of water across
a semipermeable membrane (i.e., one that
is permeable to water but impermeable to
most solutes). As water moves across the
semipermeable membrane, it generates a
pressure called the osmotic pressure.
The magnitude of the osmotic pressure
represents the hydrostatic pressure
(measured in millimeters of mercury [mm
Hg]) needed to oppose the movement of
water across the membrane.
 TONICITY
A change in water content causes
cells to swell or shrink.
The term tonicity refers to the
tension or effect that the effective
osmotic pressure of a solution with
impermeable solutes exerts on cell
size because of water movement
across the cell membrane.
Solutions to which body cells are
exposed can be classified as isotonic,
hypotonic, or hypertonic depending
on whether they cause cells to swell
or shrink.
 COMPARTMENTAL DISTRIBUTION
OF BODY FLUIDS
 Body water: 60% of body weight (about
42 L of water)
 ICF compartment: 40% of body weight
 ECF compartment : 20% of body weight

The fluid in the ECF compartment is further

divided into two major subdivisions:
 the plasma compartment: one fourth of
the ECF
 Interstitial fluid compartment: three
fourths of the ECF
 THIRD SPACE
A third, usually minor, subdivision of the ECF compartment is the transcellular compartment.
It includes:
 the cerebrospinal fluid
 fluid contained in the various body spaces, such as the peritoneal, pleural, and pericardial
cavities; the joint spaces; and the gastrointestinal tract
Normally, only approximately 1% of ECF is in the transcellular space. This amount can increase
considerably in conditions such as ascites, in which large amounts of fluid are sequestered in the
peritoneal cavity.

When the transcellular fluid compartment becomes considerably enlarged, it is referred to as a

third space, because this fluid is not readily available for exchange with the rest of the ECF.
 CAPILLARY–INTERSTITIAL FLUID EXCHANGE
The transfer of water between the
vascular and interstitial
compartments occurs at the
capillary level.
The direction and amount of fluid
that flows across the capillary wall
are determined by:
(1) the hydrostatic pressure of the
two compartments,
(2) the colloidal osmotic
pressures of the two
compartments,
(3) the removal of excess fluid and
osmotically active particles from
the interstitial spaces by the
lymphatic system
 HYDROSTATIC PRESSURE

The hydrostatic
pressure is the
pushing force
exerted by a fluid.
 COLLOIDAL OSMOTIC PRESSURE

The colloidal osmotic

pressure is the pulling
force created by the
presence of evenly
dispersed particles,
such as the plasma
proteins, that cannot
pass through the pores
of the capillary
membrane.
 LYMPH DRAINAGE

The lymphatic system represents an

accessory system by which fluid can
be returned to the circulatory system.

Any excess fluids and osmotically

active plasma proteins that may have
leaked into the interstitium are
picked up by vessels of the lymphatic
system and returned to the
circulation.

Without the function of the

lymphatic system, excessive amounts
of fluid would accumulate in the
interstitial spaces.
DISORDERS OF SODIUM AND WATER BALANCE

Disorders of sodium and water balance can be divided into two main categories:
1. Isotonic contraction or expansion of ECF volume
2. Hypotonic dilution (hyponatremia) or hypertonic concentration
(hypernatremia) of extracellular sodium brought about by changes in extracellular
water

Isotonic disorders usually are confined to the ECF compartment, producing a

contraction (fluid volume deficit) or expansion (fluid volume excess) of the
interstitial and vascular fluids.
Disorders of sodium concentration produce a change in the osmolality of the ECF,
with movement of water from the ECF compartment into the ICF compartment
(hyponatremia) or from the ICF compartment into the ECF compartment
(hypernatremia).
ISOTONIC FLUID VOLUME DEFICIT

 characterized by a decrease in the ECF, including the circulating blood volume

 losses in sodium and water are proportional
 unless other fluid and electrolyte imbalances are present, the concentration of
plasma electrolytes remains essentially unchanged
 when the effective circulating blood volume is compromised, the condition is
often referred to as hypovolemia
CAUSES OF ISOTONIC FLUID VOLUME DEFICIT
MANIFESTATIONS OF ISOTONIC FLUID
VOLUME DEFICIT
 ISOTONIC FLUID VOLUME EXCESS

Fluid volume excess

represents an isotonic
expansion of the ECF
compartment with
increases in both
interstitial and vascular
volumes.
HYPONATREMIA

Hyponatremia represents a plasma sodium concentration below 135 mmol/L.

Can present as a hypotonic or hypertonic state:
 Hypertonic (translocational) hyponatremia results from an osmotic shift of
water from the ICF to the ECF compartment, such as that occurring in
hyperglycemia. In this case, the sodium in the ECF becomes diluted as water
moves out of cells in response to the osmotic effects of the elevated blood
glucose level.
 Hypotonic (dilutional) hyponatremia, by far the most common type of
hyponatremia, is caused by water retention.
 HYPOTONIC HYPONATREMIA - CAUSES

Hypovolemic (decreased serum sodium with decreased ECF volume):

 Use of excessively diluted infant formula
 Administration of sodium-free parenteral solutions
 GI losses: vomiting, diarrhoea
 Sweating with sodium-free fluid replacement
 Repeated irrigation of body cavities with sodium free solutions (GI tubes with dilated
water, tap water enemas)
 Third spacing (paralytic ileus, pancreatitis)
 Diuretic use
 Addison disease
 Salt-wasting nephritis
 HYPOTONIC HYPONATREMIA - CAUSES

Euvolemic (decreased serum sodium with normal ECF volume):

 Increased ADH levels (trauma, stress, pain, drugs)
 Diuretic use
 Glucocorticosteroid deficiency
 Hypothyroidism
 Psychogenic polydypsia
 MDMA (ecstasy) abuse

Hypervolemic (decreased serum sodium with increased ECF volume):

 Decompensated heart failure
 Advanced liver disease
 Kidney failure with nephrosis
HYPONATREMIA -
MANIFESTATIONS
HYPERNATREMIA

Hypernatremia implies a plasma sodium level above 145 mmol/L.

Because sodium is functionally an impermeable solute, it contributes to tonicity
and induces movement of water across cell membranes.
Hypernatremia is characterized by hypertonicity of ECF and almost always causes
cellular dehydration.
Hypernatremia represents a deficit of water in relations to the body’s sodium
stores. It can be caused by net loss of water or sodium gain.
HYPERNATREMIA -
CAUSES
HYPERNATREMIA -
MANIFESTATIONS
POTASSIUM BALANCE

 Potassium is the second most abundant cation in the body

 The major cation in the ICF compartment
 Approximately 98% of body potassium is contained within body cells
 Potassium intake is normally derived from dietary sources
 Additional amounts of potassium are needed during periods of trauma and stress.
 The kidneys are the main source of potassium loss. Approximately 80% to 90% of
potassium losses occur in the urine, with the remainder being lost in stools or
sweat.
 Many cell functions are sensitive to even small changes in ECF potassium levels
MECHANISMS OF REGULATION

Plasma potassium is largely regulated through two mechanisms:

(1) renal mechanisms that conserve or eliminate potassium
(2) a transcellular shift between the ICF and ECF compartments
RENAL REGULATION

Unlike other electrolytes, the

regulation of potassium elimination is
controlled by secretion from the blood
into the tubular filtrate rather than
through reabsorption from the tubular
filtrate into the blood.
Aldosterone plays an essential role in
regulating potassium elimination by
the kidney. In the presence of
aldosterone, Na+ is transported back
into the blood and K+ is secreted in
the tubular filtrate for elimination in
the urine.
 EXTRACELLULAR–INTRACELLULAR SHIFTS
Factors that alter the intracellular–extracellular distribution
of potassium:
 serum osmolality - acute increases in serum osmolality
cause water to leave the cell; an increase in intracellular
potassium results in shifting out of the cell into the ECF
 acid–base disorders - in metabolic acidosis, for example,
H+ moves into body cells for buffering, causing K+ to leave
and move into the ECF
 Insulin - produces an increase in cellular uptake of
potassium after a meal
 β-adrenergic stimulation - the catecholamines, particularly
epinephrine, facilitate the movement of potassium into
muscle tissue during periods of physiologic stress (also β-
adrenergic agonist drugs, such as pseudoephedrine and
albuterol)
 exercise - repeated muscle contraction releases potassium
into the ECF.
DISORDERS OF POTASSIUM BALANCE
DISORDERS OF POTASSIUM BALANCE

Potassium is critical to many body functions:

 the maintenance of the osmotic integrity of cells, acid–base balance, and the
kidney’s ability to concentrate urine
 potassium is necessary for growth
 it contributes to the intricate chemical reactions that transform carbohydrates
into energy, change glucose into glycogen, and convert amino acids to proteins.
 potassium plays a critical role in conducting nerve impulses and the excitability of
skeletal, cardiac, and smooth muscle (particularly important in the heart, where
alterations in plasma potassium can produce serious cardiac arrhythmias and
conduction defects)
HYPOKALEMIA
HYPOKALEMIA -
MANIFESTATIONS
HYPERKALEMIA
HYPERKALEMIA -
MANIFESTATIONS
FROM THEORY TO REAL LIFE
GROSS STRUCTURE AND LOCATION
RENAL
BLOOD
SUPPLY
 THE NEPHRON

Each nephron consists of:

• a glomerulus,
• a proximal convoluted tubule,
• a loop of Henle,
• a distal convoluted tubule,
• a collecting duct.
THE GLOMERULUS

• unique, high-pressure capillary

filtration system
• located between two arterioles,
the afferent and the efferent
arterioles
• the blood pressure in the
glomerulus is extraordinarily high
for a capillary bed and easily forces
fluid and solutes out of the blood
into the glomerular capillary along
its entire length
 THE GLOMERULUS

 The glomerulus consists of a compact tuft of

capillaries encased in a thin, double-walled
capsule called Bowman capsule.
 Blood flows into the glomerular capillaries from
the afferent arteriole and flows out of the
glomerular capillaries into the efferent arteriole,
which leads into the peritubular capillaries.
 Fluid and particles from the blood are filtered
through the capillary membrane into a fluid-
filled space in Bowman capsule, called Bowman
space.
 The portion of the blood that is filtered into the
capsule space is called the filtrate.
 THE MESANGIUM

The function of mesangial cells:

 production of intercellular substance similar
to that of the basement membranę - this
substance covers the endothelial cells where
they are not covered by basement membrane
 the mesangial cells possess phagocytic
properties and remove macromolecular
materials that enter the intercapillary spaces
 the mesangial cells also exhibit contractile
properties in response to neurohumoral
substances and are thought to contribute to
the regulation of blood flow through the
glomerulus
THE PERITUBULAR
CAPILLARIES

 originate from the efferent arteriole

 they are low-pressure vessels that
are adapted for reabsorption rather
than filtration
 the peritubular capillaries rejoin to
form the venous channels by which
blood leaves the kidneys and
empties into the inferior vena cava
URINE FORMATION

Urine formation involves the

filtration of blood by the
glomerulus to form an
ultrafiltrate of urine and the
tubular reabsorption of
electrolytes and nutrients
needed to maintain the
constancy of the internal
environment while
eliminating waste materials.
ANTIDIURETIC HORMONE (ADH)

 regulates the ability of the kidneys to concentrate urine

 is synthesized by neurons in the hypothalamus and
transported down their axons to the posterior pituitary
gland and then released into the circulation
 one of the main stimuli for synthesis and release of ADH is
an increase in serum osmolarity
 ADH release is also controlled by cardiovascular reflexes
that respond to changes in blood pressure or blood volume
REGULATION OF RENAL BLOOD FLOW

Neural and Humoral Control

Autoregulatory Mechanisms
Mechanisms
• sympathetic stimulation • the juxtaglomerular complex -
• humoral substances: a feedback control system
angiotensin II, ADH, and the that links changes in the GFR
endothelins - produce (glomerular filtration rate)
vasoconstriction of renal with renal blood flow
vessels; dopamine, nitric
oxide, and prostaglandins -
produce vasodilation
THE JUXTAGLOMERULAR
COMPLEX
• located at the site where the distal
tubule extends back to the
glomerulus and then passes between
the afferent and efferent arterioles

• essential feedback role in linking the

level of arterial blood pressure and
renal blood flow to the GFR and the
composition of the distal tubular
fluid
CONDITIONS THAT CAN INCREASE RENAL
BLOOD FLOW AND GLOMERULAR FILTRATION

1. an increased amount of protein in the diet

2. an increase of blood glucose level
 ELIMINATION FUNCTIONS
OF THE KIDNEY

 elimination of sodium and potassium

 regulation of body pH by conserving base bicarbonate and eliminating hydrogen ions (H+)
 uric acid elimination - uric acid is a product of purine metabolism; excessively high blood
levels (i.e., hyperuricemia) can cause gout, and excessive urine levels can cause kidney
stones
 urea elimination - urea is an end product of protein metabolism; the quantity rises when a
high-protein diet is consumed, when there is excessive tissue breakdown, or in the
presence of gastrointestinal bleeding
 drug elimination
 ENDOCRINE FUNCTIONS OF THE KIDNEY

The kidneys function as an endocrine organ in

that they produce chemical mediators that travel
through the blood to distant sites where they
exert their actions.
The kidneys participate in control of blood
pressure in the following ways:
 via the renin–angiotensin–aldosterone
mechanism
 via regulation of red blood cell production
through the synthesis of erythropoietin
 via calcium metabolism by activating vitamin
D
CONGENITAL DISORDERS OF THE KIDNEYS

 Dysgenesis refers to a failure of an organ to develop normally

 Agenesis refers to failure of an organ to develop at all.
 In renal hypoplasia, the kidneys do not develop to normal size.
 Renal dysplasia is caused by an abnormality in the differentiation of kidney
structures during embryonic development. It is characterized by undifferentiated
tubular structures surrounded by primitive embryonic tissue. The disorder may
result in small, aplastic kidneys or cysts that form from the abnormal tubules. If
cysts are present, the condition is referred to as cystic dysplasia.
 Ectopic kidneys lie outside their normal position. One or both kidneys may be in
an abnormal position. Most ectopic kidneys are located within the pelvis, but
some lie in the inferior part of the abdomen. Because of the abnormal position,
kinking of the ureters and obstruction of urinary flow may occur.
A – agenesis
B – dysplasia
C - hypoplasia
HORSESHOE KIDNEY

 occurs in approximately 1 of every

500 to 1000 people
 the upper or lower poles of the two
kidneys are fused, producing a
horseshoe-shaped structure that is
continuous along the midline of the
body anterior to the great vessels
 INHERITED CYSTIC
KIDNEY DISEASES

 Polycystic kidney diseases are a group of

kidney disorders characterized by fluid-filled
sacs or segments that have their origin in
the tubular structures of the kidney.

 The cysts may be single or multiple and can

vary in size from microscopic to several
centimeters in diameter.

 Most forms are hereditary.

 AUTOSOMAL DOMINANT POLYCYSTIC
KIDNEY DISEASE
 the progress of the disease is slow, and ESRD is uncommon for adults before 40 years of age
 initially, cysts are generally asymptomatic, and kidney and liver function are normal
 as the kidney disease progresses, the manifestations of ADPD include pain from the
enlarging cysts, episodes of gross hematuria from bleeding into a cyst, infected cysts from
ascending UTIs, and hypertension resulting from compression of intrarenal blood vessels with
activation of the renin–angiotensin mechanism
 the kidneys may achieve enormous sizes
 cysts also may be found in the liver and, less commonly, in the pancreas and spleen
 approximately 20% of people with polycystic kidney disease have an associated aneurysm,
and subarachnoid hemorrhage (SAH) is a frequent cause of death.
 SIMPLE RENAL CYSTS

Simple cysts are a common disorder of the kidney:

 they may be single or multiple, unilateral or bilateral
 they usually are less than 1 cm in diameter
 most simple cysts do not produce signs or symptoms or compromise renal function
 when symptomatic, the cysts may cause flank pain, hematuria, infection, and hypertension
 they are most common in older adults
 although the cysts are benign, they may be confused clinically with renal cell carcinoma
 ACQUIRED RENAL CYSTS

 an acquired form of renal cystic disease

occurs in people with end stage renal
failure (ESRF) who have undergone
prolonged dialysis treatment
 although the condition is largely
asymptomatic, the cysts may bleed,
causing hematuria
 tumors, usually adenomas but
occasionally adenosarcomas, may
develop in the walls of these cysts
OBSTRUCTIVE DISORDERS

 urinary obstruction can occur in people of any age

 can involve any level of the urinary tract, from the
urethra to the renal pelvis
 may be sudden or insidious, partial or complete,
and unilateral or bilateral
 the conditions that cause urinary tract obstruction
include congenital anomalies, urinary calculi (i.e.,
stones), pregnancy, benign prostatic hyperplasia,
scar tissue resulting from infection and
inflammation, tumors, and neurologic disorders
such as spinal cord injury
 OBSTRUCTIVE DISORDERS

Obstructive uropathy is usually classified according to site, degree, and duration of obstruction:
▪ lower urinary tract obstructions are located below the ureterovesical junction and are bilateral in nature,
▪ upper urinary tract obstructions are located above the ureterovesical junction and are usually unilateral,
▪ the condition causing the obstruction can cause complete or partial occlusion of urine outflow,
▪ when the obstruction is of short duration (i.e., less than a few days), it is said to be acute and is usually
caused by conditions such as renal calculi,
▪ an obstruction that develops slowly and is longer lasting is said to be chronic and is usually caused by
conditions such as congenital ureterovesical abnormalities,
▪ bilateral acute urinary tract obstruction causes acute renal failure.
Because many causes of acute obstruction are reversible, prompt recognition is important. When left
untreated, an obstructed kidney undergoes atrophy, and in the case of bilateral obstruction, results in
chronic renal failure.
OBSTRUCTIVE DISORDERS

The two most damaging effects of urinary obstruction are:

1. stasis of urine, which predisposes to infection and stone formation
2. progressive dilation of the renal collecting ducts and renal tubular structures,
which causes destruction and atrophy of renal tissue.

Hydronephrosis refers to urine-filled dilation of the renal pelvis and calices

associated with progressive atrophy of the kidney due to obstruction of urine
outflow.
HYDRONEPHROSIS
 RENAL CALCULI

 the most common cause of upper

urinary tract obstruction
 stones can form in any part of the
urinary tract (most develop in the
kidneys)
 renal calculi or kidney stones are a
common diagnosis occurring in the
urinary tract, exceeded only by UTIs
and prostate disorders
URINARY TRACT INFECTIONS (UTI)

UTIs include several distinct entities, including:

 asymptomatic bacteriuria
 symptomatic infections
 lower UTIs such as cystitis
 upper UTIs such as pyelonephritis
Because of their ability to cause renal damage, upper UTIs are considered more
serious than lower UTIs. Acute pyelonephritis represents an infection of the renal
parenchyma and renal pelvis. Improperly treated, it can lead to sepsis, renal
abscesses, chronic pyelonephritis, and chronic renal failure.
URINARY TRACT INFECTIONS (UTI)

 Most UTIs are caused by bacteria that enter through the urethra.
 Bacteria can also enter through the bloodstream usually in immunocompromised
people and neonates.
 Although the distal portion of the urethra often contains pathogens, the urine
formed in the kidneys and found in the bladder normally is sterile or free of
bacteria. This is because of the washout phenomenon, in which urine from the
bladder normally washes bacteria out of the urethra.
 When a UTI occurs, it is usually from bacteria that have colonized the urethra,
vagina, or perianal area.
 URINARY TRACT INFECTIONS (UTI)

An increased risk for UTIs:

 in people with urinary obstruction and reflux,
 in people with neurogenic disorders that impair bladder emptying,
 in women who are sexually active,
 in postmenopausal women,
 in men with diseases of the prostate,
 in older adults
Instrumentation and urinary catheterization are common predisposing factors for UTIs.
UTIs occur more commonly in women with diabetes than in women without the disease (due to their
alkaline urine). People with diabetes are also at increased risk for complications associated with UTIs,
including pyelonephritis, and they are more susceptible to fungal infections (particularly Candida species)
and infections with gram-negative pathogens other than E. coli.
URINARY TRACT INFECTIONS (UTI)

In UTIs associated with stasis of urine flow, the obstruction may be:
 anatomic - include urinary tract stones, prostatic hyperplasia, pregnancy, and
malformations of the ureterovesical junction
 functional - include neurogenic bladder, infrequent voiding, detrusor (bladder)
muscle instability, and constipation
 REFLUX

 Urethrovesical reflux - occurs when urine from the

urethra moves into the bladder, In women can occur
during activities such as coughing or squatting, in which
an increase in intra-abdominal pressure causes the urine
to be squeezed into the urethra and then to flow back
into the bladder as the pressure decreases.
 Vesicoureteral reflux - occurs at the level of the bladder
and ureter. It is seen most commonly in children with
UTIs (result from congenital defects in length, diameter,
muscle structure, or innervation of the submucosal
segment of the ureter), and also is seen in adults with
obstruction to bladder outflow, primarily due to
increased bladder volume and pressure.
VESICOURETERAL REFLUX
DISORDERS OF
GLOMERULAR FUNCTION
 The glomerular capillary membrane is
selectively permeable, allowing water and
small particles (e.g., electrolytes, and dissolved
particles, such as glucose and amino acids) to
leave the blood and enter the Bowman space
and preventing larger particles (e.g., plasma
proteins and blood cells) from leaving the
blood.
 Glomerulonephritis, an inflammatory process
that involves glomerular structures, is the
second leading cause of kidney failure
worldwide and it ranks third, after diabetes
and hypertension, as a cause of chronic kidney
disease
DISORDERS OF GLOMERULAR FUNCTION

The disease may occur as a:

 primary condition – the glomerular abnormality is the only disease present
 secondary condition – the glomerular abnormality results from another disease,
such as diabetes mellitus or SLE

The causative agents or triggering events that produce glomerular injury include:
 immunologic mechanisms
 nonimmunologic mechanisms – metabolic (e.g., diabetes), hemodynamic (e.g.,
hypertension), and toxic (e.g., drugs, chemicals)
 hereditary mechanisms
DISORDERS OF GLOMERULAR FUNCTION

The cellular changes that occur with glomerular disease include:

 increases in glomerular or inflammatory cell number (proliferative or hypercellular)
 basement membrane thickening (membranous)
 changes in noncellular glomerular components (sclerosis and fibrosis)

Glomerular changes can be:

 diffuse - involving all glomeruli and all parts of the glomeruli
 focal - in which only some glomeruli are affected and others are essentially normal
 segmental - involving only a certain segment of each glomerulus
 mesangial - affecting only mesangial cells
TYPES OF GLOMERULAR DISEASE

The clinical manifestations of glomerular disorders generally fall into one of five
categories:
1. Nephritic syndromes
2. Rapidly progressive glomerulonephritis
3. The nephrotic syndrome
4. Asymptomatic disorders of urinary sediment (i.e.,hematuria, proteinuria)
5. Chronic glomerulonephritis
 ACUTE NEPHRITIC SYNDROME

 The acute nephritic syndrome is the clinical

correlate of acute glomerular inflammation
 Inflammatory processes that occlude the
glomerular capillary lumen and damage the
capillary wall
 Typically is associated with acute
proliferative glomerulonephritis such as
postinfectious glomerulonephritis
 May occur in such systemic diseases as SLE
 Characterized by sudden onset of
hematuria, variable degrees of proteinuria,
diminished GFR, oliguria, and signs of
impaired renal function
ACUTE POSTINFECTIOUS
GLOMERULONEPHRITIS
 usually occurs after infection with certain strains of group A β-hemolytic
streptococci (may also occur after infections by other organisms, including
staphylococci, a viral agent, such as hepatitis, and various parasites)
 Is caused by deposition of immune complexes of antibody and bacterial antigens
the disease
 is seen primarily in children, but people of any age can be affected
 the classic case of poststreptococcal glomerulonephritis follows a streptococcal
infection by approximately 7 to 12 days (this is the time needed for the
development of antibodies)
 oliguria is one of the first symptoms; proteinuria and hematuria follow because of
increased glomerular capillary wall permeability
RAPIDLY PROGRESSIVE
GLOMERULONEPHRITIS
 a clinical syndrome characterized by signs of
severe glomerular injury that does not have a
specific cause
 this type of glomerulonephritis is rapidly
progressive, often within a matter of months
 involves focal and segmental proliferation of
glomerular cells and recruitment of monocytes
and macrophages with formation of crescent-
shaped structures that obliterate the Bowman
space
 may be caused by a number of immunologic
disorders, some systemic and others restricted
to the kidney (SLE, small-vessel vasculitides
(e.g., microscopic polyangiitis), and Goodpasture
syndrome)
RAPIDLY PROGRESSIVE
GLOMERULONEPHRITIS

(a) Normal glomerulus

(b) Glomerular disease leads to
gaps or holes in the
glomerular basement
membrane (GBM), resulting
in (c) proliferation of parietal
epithelial cells and ultimately
(d) fibrocellular crescent
formation
 NEPHROTIC SYNDROME

The nephrotic syndrome is not a specific glomerular

disease, but a constellation of clinical findings that
result from an increase in glomerular permeability
and loss of plasma proteins in the urine.
Is characterized by:
 massive proteinuria (>3.5 g/day)
 lipiduria (e.g., free fat, oval bodies, fatty casts)
 hypoalbuminemia (<3 g/dL)
 generalized edema
 hyperlipidemia (cholesterol > 300 mg/dL)
 NEPHROTIC SYNDROME

 can develop as a primary disorder or

secondary to changes caused by
systemic diseases such as diabetes
mellitus and SLE
 among the primary glomerular lesions
are minimal-change disease (lipoid
nephrosis), focal segmental
glomerulosclerosis, and membranous
glomerulonephritis
 in children younger than 15 years of age,
nephrotic syndrome almost always is
caused by primary idiopathic glomerular
disease, whereas in adults, it often is a
secondary disorder
FOCAL SEGMENTAL
GLOMERULOSCLEROSIS

(a) Normal glomerulus.

(b) Podocyte loss or injury (e.g.,
from increased glomerular
capillary pressure) leads to
denuded areas of GBM,
which leads to formation of a
tuft adhesion. (c) This
subsequently leads to the
formation of a sclerotic area,
the first step in development
of glomerulosclerosis and
hyalinosis with obliteration
of adjacent capillary loops.
ASYMPTOMATIC HEMATURIA OR
PROTEINURIA
Many cases of glomerulonephritis result in mild asymptomatic illness that is not
recognized or brought to the attention of a health care professional, and therefore
remains undiagnosed.
IgA nephropathy is the most common glomerulonephritis worldwide.Primary IgA
nephropathy is characterized by deposition of the IgA antibody in the glomerulus.
There are other diseases associated with glomerular IgA deposits, the most
common being IgA vasculitis (formerly known as Henoch–Schönlein purpura
[HSP]), which is considered by many to be a systemic form of IgA nephropathy.
Disorders such as Henoch-Schönlein purpura often resolve without permanent
kidney damage, whereas others, such as IgA nephropathy and Alport syndrome,
can progress to chronic kidney disease and renal failure.
HENOCH-SCHÖNLEIN PURPURA NEPHRITIS

 small-vessel vasculitis that causes a purpuric rash largely of the lower extremities,
arthritis or arthralgia, abdominal pain, and renal involvement
 most commonly in children
 hematuria and proteinuria are the most common presentation
 most people recover fully over a period of several weeks
IGA
NEPHROPATHY

(a) IgA deposition

between mesangial
cells is followed by (b)
proliferation of
mesangial cells, which
leads to (c) mesangial
hypercellularity and
matrix expansion
CHRONIC GLOMERULONEPHRITIS

 represents the chronic phase of a number of specific types of glomerulonephritis

 some forms of acute glomerulonephritis (e.g., poststreptococcal
glomerulonephritis) undergo complete resolution, whereas others progress at
variable rates to chronic glomerulonephritis
 histologically, the condition is characterized by small kidneys with sclerosed
glomeruli
 in most cases, chronic glomerulonephritis develops insidiously and slowly
progresses to chronic kidney disease over a period of years
GLOMERULAR LESIONS ASSOCIATED
WITH SYSTEMIC DISEASE

 Systemic Lupus Erythematosus Glomerulonephritis

 Diabetic Glomerulosclerosis
 Hypertensive Glomerular Disease
 DIABETIC GLOMERULOSCLEROSIS

Diabetic nephropathy is a major cause of chronic kidney disease and the

most common cause of kidney failure treated by renal replacement
therapy
It occurs in both types 1 and 2 diabetes mellitus
The lesions of diabetic nephropathy most commonly involve the
glomeruli:
 widespread thickening of the glomerular capillary basement
membrane with diffuse increase in mesangial matrix, with mild
proliferation of mesangial cells (as the disease progresses, the
mesangial cells impinge on the capillary lumen, reducing the surface
area for glomerular filtration)
 in nodular glomerulosclerosis, also known as Kimmelstiel-Wilson
syndrome, there is nodular deposition of hyaline in the mesangial
portion of the glomerulus (as the sclerotic proces progresses in the
diffuse and nodular forms of glomerulosclerosis, there is complete
obliteration of the glomerulus, with impairment of renal function)
HYPERTENSIVE GLOMERULAR DISEASE

Mild to moderate hypertension causes sclerotic changes in renal arterioles and

small arteries, referred to as benign nephrosclerosis.
 The kidneys are smaller than normal and are usually affected bilaterally.
 On histologic examination, there is narrowing of the arterioles and small arteries,
caused by thickening and scarring of the vessel walls.
 As the vascular structures thicken and perfusion diminishes, blood flow to the
nephron decreases, causing patchy tubular atrophy, interstitial fibrosis, and a
variety of changes in glomerular structure and function.
TUBULOINTERSTITIAL DISORDERS

❑ acute tubular necrosis

❑ renal tubular acidosis
❑ acute and chronic pyelonephritis
❑ the effects of drugs and toxins
 TUBULOINTERSTITIAL RENAL DISEASES

Acute Chronic
produce interstitial fibrosis, atrophy,
sudden onset
and mononuclear infiltrates
signs and symptoms of interstitial asymptomatic until late in the course
edema of the disease
include acute pyelonephritis and in the early stages manifested by fluid
acute hypersensitivity reaction to and electrolyte imbalances that
drugs reflect changes in tubular function
PYELONEPHRITIS

Pyelonephritis refers to infection of the kidney parenchyma and renal pelvis.

There are two forms of pyelonephritis:
 acute
 chronic
 ACUTE PYELONEPHRITIS

Etiology: Gram-negative bacteria, including E. coli and Proteus,

Klebsiella, Enterobacter, and Pseudomonas species.
The infection usually ascends from the lower urinary tract (with
the exception of S. aureus, which is usually spread through the
bloodstream).
Factors that contribute to the development of acute
pyelonephritis are:
 catheterization and urinary instrumentation
 vesicoureteral reflux
 pregnancy
 neurogenic bladder
Hematogenous acute pyelonephritis occurs most often in
debilitated, chronically ill people and those receiving
immunosuppressive therapy.
ACUTE PYELONEPHRITIS
 NECROTIZING PYELONEPHRITIS
(NECROTIZING PAPILLITIS)

A less frequent and more serious type of

acute pyelonephritis.

Characterized by necrosis of the renal

papillae.

It is particularly common in people with

diabetes and may also be a complication
of acute pyelonephritis when there is
significant urinary tract obstruction.
NECROTIZING PYELONEPHRITIS
(NECROTIZING PAPILLITIS)
 CHRONIC PYELONEPHRITIS

 scarring and deformation of the renal calyces and

pelvis
 recurrent bouts of inflammation and scarring, which
eventually lead to chronic pyelonephritis
 reflux, which is the most common cause of chronic
pyelonephritis, results from superimposition of
infection on congenital vesicoureteral reflux or
intrarenal reflux
 reflux may be unilateral with involvement of a single
kidney or bilateral, leading to scarring and atrophy of
both kidneys with the eventual development of
chronic renal insufficiency
 DRUG-RELATED NEPHROPATHIES

Functional or structural changes in the kidneys that occur after exposure to a drug.

Drugs and toxic substances can damage the kidneys by:

 causing a decrease in renal blood flow (diuretics, high molecular weight radiocontrast
media, the immunosuppressive drugs cyclosporine and tacrolimus, the nonsteroidal
anti-inflammatory drugs (NSAIDs))
 obstructing urine flow (sulfonamides and vitamin C (due to oxalate crystals) can form
crystals that cause kidney damage by obstructing urinary flow in the tubules)
 directly damaging tubulointerstitial structures (NSAIDs)
 producing hypersensitivity reactions (most often with the use of methicillin and other
synthetic antibiotics, and with the use of furosemide and the thiazide diuretics in
persons sensitive to these drugs)
MALIGNANT TUMORS OF THE KIDNEY

There are two major groups of malignant tumors of the kidney:

 embryonic kidney tumors (i.e., Wilms tumor), which occur during childhood
 renal cell carcinoma, which occurs in adults
WILMS TUMOR (NEPHROBLASTOMA)

❑ one of the most common primary neoplasms of young children

❑ usually presents between 3 and 5 years of age
❑ the most common malignant abdominal tumor in children
❑ may occur in one or both kidneys
❑ the incidence of bilateral Wilms tumor is 5% in sporadic cases and up to 20% in familial cases

An important feature of Wilms tumor is its association with other congenital anomalies:
 aniridia (absence of the iris)
 hemihypertrophy (enlargement of one side of the face or body)
 other congenital anomalies, usually of the genitourinary system
WILMS TUMOR (NEPHROBLASTOMA)
 RENAL CELL CARCINOMA

 accounts for approximately 80% to 90% of kidney

tumors
 may arise from any portion of the kidney, but most
commonly affects the poles, especially the upper pole
 risk factors: heavy smoking, obesity, acquired cystic
kidney disease associated with chronic renal
insufficiency
 gross or microscopic hematuria, which occurs in the
majority of cases, is an important clinical clue
 the tumor may reach considerable size before it is
detected
 RENAL FAILURE

Renal failure is a condition in which the kidneys fail to remove metabolic end products
from the blood and regulate the fluid, electrolyte, and pH balance of the extracellular
fluids.
The underlying cause may be renal disease, systemic disease, or urologic defects of
nonrenal origin.
Renal failure can occur as:
 an acute disorder - abrupt in onset, often reversible if recognized early and treated
appropriately
 a chronic disorder - the end result of irreparable damage to the kidneys, develops
slowly, over the course of a number of years (80% of the nephrons need to be
nonfunctioning before the symptoms of chronic kidney disease are manifested)
 ACUTE RENAL INJURY
(ACUTE RENAL FAILURE)
 rapid decline in kidney function sufficient to increase blood levels of nitrogenous wastes
and impair fluid and electrolyte balance
 potentially reversible if the precipitating factors can be corrected or removed before
permanent kidney damage has occurred

The most common indicator of AKI is:

 azotemia - an accumulation of nitrogenous wastes (urea nitrogen, uric acid, and
creatinine) in the blood
 decrease in the glomerular filtration rate (GFR)
 TYPES OF ACUTE RENAL INJURY

The causes of acute

renal failure commonly
are categorized as:
 prerenal
 intrarenal
 postrenal

Collectively, prerenal
and intrarenal causes
account for 80% to 95%
of acute renal failure
cases.
 PRERENAL FAILURE

 the most common form of acute

renal failure
 characterized by a marked decrease
in renal blood flow
 reversible if the cause of the
decreased renal blood flow can be
identified and corrected before
kidney damage occurs
 manifested by a sharp decrease in
urine output and a disproportionate
elevation of blood urea nitrogen
(BUN) in relation to serum
creatinine levels
 POSTRENAL FAILURE

 results from obstruction of urine outflow from the kidneys

 the obstruction can occur in the ureter (i.e., calculi and
strictures), bladder (i.e., tumors or neurogenic bladder), or
urethra (i.e., prostatic hyperplasia)
 due to the increased urine not being able to be excreted
due to the obstruction, retrograde pressure occurs
throughout the tubules and nephrons, which ultimately
damages the nephrons
 prostatic hyperplasia is the most common underlying
problem
 both ureters must be occluded to produce renal failure
 INTRARENAL RENAL FAILURE
(ACUTE KIDNEY INJURY)
 results from conditions that cause
damage to structures within the kidney
 the most frequent etiology of intrarenal
acute renal failure causes damage to the
parenchyma in the glomeruli, vessels,
tubules, or interstitium
 the major causes of intrarenal failure are
ischemia associated with prerenal failure,
toxic insult to the tubular structures of the
nephron, and intratubular obstruction
 acute glomerulonephritis and acute
pyelonephritis also are intrarenal causes
of acute renal failure
INTRARENAL RENAL FAILURE
(ACUTE KIDNEY INJURY)
The decreased glomerular filtration and epithelial injury are due to many causes:
 intrarenal vasoconstriction
 decreased hydrostatic pressure in the glomeruli
 changes in arterial tone by tubuloglomerular feedback
 decreased capillary permeability in the glomeruli
 increased tubular hydrostatic pressure secondary to obstruction
 backflow of glomerular filtrate into the interstitium
Injury to the tubular structures of the nephron is the most common cause and often
is ischemic or toxic in origin.
ACUTE TUBULAR INJURY
(NECROSIS)

 destruction of tubular epithelial cells with

acute suppression of renal function
 tubular epithelial cells are particularly
sensitive to ischemia and also are
vulnerable to toxins
 the tubular injury that occurs frequently is
reversible
 can be caused by a variety of conditions,
including acute tubular damage due to
ischemia, sepsis, nephrotoxic effects of
drugs, tubular obstruction, and toxins
from a massive infection
 ACUTE TUBULAR INJURY (NECROSIS)

Ischemic ATN
• in contrast to prerenal failure, the GFR does not improve with the restoration of renal blood flow
• causes: extensive surgery, severe hypovolemia, sepsis, trauma, or burns

Toxic ATN
• tubular injury is caused by inducing varying combinations of renal vasoconstriction, direct tubular
damage, or intratubular obstruction
• pharmacologic agents that are directly toxic to the renal tubule: antimicrobials such as
aminoglycosides (e.g., vancomycin, gentamicin), cancer chemotherapeutic agents such as
cisplatin and radiocontrast agents
• most frequent causes due to intratubular obstruction: the presence of myoglobin, hemoglobin,
uric acid, myeloma light chains, or excess uric acid in the urine
 ACUTE TUBULAR INJURY

The course of ATN or acute tubular

injury can be divided into three phases:
1. Onset or initiating phase - lasts hours
or days, is the time from the onset of
the precipitating event (e.g., ischemic
phase of prerenal failure or toxin
exposure) until tubular injury occurs
2. Maintenance phase - characterized
by a marked decrease in the GFR,
causing sudden retention of
endogenous metabolites, such as urea,
potassium, sulfate, and creatinine, that
normally are cleared by the kidneys
3. Recovery or convalescent phase - the
period during which repair of renal
tissue takes place
CHRONIC KIDNEY
DISEASE (CKD)
 CKD represents the progressive decline in kidney
function due to the permanent loss of nephrons
 CKD can result from a number of conditions,
including diabetes, hypertension,
glomerulonephritis, and other kidney diseases
 the GFR is considered the best measure of kidney
function
Regardless of cause, CKD represents a loss of
functioning kidney nephrons with progressive
deterioration of glomerular filtration, tubular
reabsorptive capacity, and endocrine functions of
the kidneys. All forms of CKD are characterized by
a reduction in the GFR, reflecting a corresponding
reduction in the number of functional nephrons.
CLINICAL MANIFESTATIONS OF CKD

The manifestations of CKD include:

 an accumulation of nitrogenous wastes;
 alterations in water, electrolyte, and acid–base balance;
 mineral and skeletal disorders;
 anemia and coagulation disorders;
 hypertension and alterations in cardiovascular function;
 gastrointestinal disorders;
 neurologic complications;
 disorders of skin integrity;
 disorders of immunologic function
ACCUMULATION
OF NITROGENOUS WASTES
Uremia, which literally means “urine in the blood,” is the term used to describe the
clinical manifestations of kidney failure. Few symptoms of uremia appear until at
least two thirds of the kidney’s nephrons have been destroyed.
Uremia differs from azotemia, which merely indicates the accumulation of
nitrogenous wastes in the blood and can occur without symptoms.
The uremic state includes signs and symptoms of altered fluid, electrolyte, and
acid–base balance; alterations in regulatory functions (e.g., blood pressure control,
production of red blood cells, and impaired vitamin D synthesis); and the effects of
uremia on body function (e.g., uremic encephalopathy, peripheral neuropathy,
pruritus). At this stage, virtually every organ and structure in the body is affected.
 FLUID, ELECTROLYTE, AND ACID–BASE
DISORDERS

 dehydration or fluid overload, depending on the pathologic process of the kidney disease
 diminished ability of the kidneys to concentrate the urine
 reduced ability to regulate sodium excretion (salt wasting is a common problem in
advanced kidney failure because of impaired tubular reabsorption of sodium)
 hyperkalemia (usually does not develop until kidney function is severely compromised)
 metabolic acidosis (may occur when the person is challenged with an excessive acid load or
loses excessive alkali, as in diarrhea)
DISORDERS OF CALCIUM AND PHOSPHORUS
METABOLISM AND BONE DISEASE

With deteriorating renal function, phosphate

excretion is impaired, and as a result serum
phosphate levels rise.

At the same time, serum calcium levels, which are

inversely regulated in relation to serum phosphate
levels, fall.

The drop in serum calcium, in turn, stimulates

parathyroid hormone (PTH) release, with a
resultant increase in calcium resorption from bone.
 SKELETAL DISORDERS

The term renal osteodystrophy or CKD-Mineral Bone Disorder is used to describe the skeletal
complications of CKD.
The skeletal changes that occur with CKD have been divided into two major types of disorders:
❑ High-bone-turnover osteodystrophy (osteitis fibrosa) - is characterized by increased bone
resorption and formation, with bone resorption predominating (mineralization fails to keep pace,
decrease in bone density, formation of porous and coarse-fibered bone, bone marrow fibrosis).
❑ Low-bone-turnover osteodystrophy - low rate of bone turnover and an accumulation of
unmineralized bone matrix:
▪ Osteomalacia is characterized by a slow rate of bone formation and defects in bone mineralization,
which may be caused by vitamin D deficiency, excess aluminum deposition, or metabolic acidosis.
▪ Adynamic osteodystrophy, is characterized by a low numer of osteoblasts, with the osteoclast number
being normal or reduced. It is especially common among persons with diabetes. Adynamic bone
disease is characterized by reduced bone volume and mineralization
HEMATOLOGIC DISORDERS

• chronic blood loss,

• hemolysis,
Anemia • bone marrow suppression due to retained uremic factors,
• and decreased red cell production due to impaired production
of erythropoietin and iron deficiency

• platelet production often is normal in CKD, but platelet function

is impaired due to uremia
Coagulopathies
CARDIOVASCULAR DISORDERS

 Hypertension
 Heart disease (due to extracellular fluid overload, shunting of blood through an
arteriovenous fistula for dialysis, and anemia)
 Pericarditis (due to the uremia and prolonged dialysis)
 OTHER DISORDERS

 Gastrointestinal disorders: anorexia, nausea, and vomiting are common in people with
uremia, along with a metallic taste in the mouth that further depresses the appetite
 Neuromuscular disorders: peripheral neuropathy caused by atrophy and demyelination
of nerve fibers (possibly due to uremic toxins), uremic encephalopathy
 Altered immune function: all aspects of inflammation and immune function may be
affected adversely by the high levels of urea and metabolic wastes, including a decreased
granulocyte count, impaired humoral and cell-mediated immunity, and defective
phagocyte function (in people who are maintained on dialysis, vascular access devices are
common portals of entry for pathogens)
 Disorders of skin integrity: pale skin (owing to anemia),may have a sallow, yellow-brown
hue; the skin and mucous membranes often are dry (reduction in perspiration owing to the
decreased size of sweat glands and the diminished activity of oil glands), subcutaneous
bruising common, pruritus is common (due to high serum phosphate levels and the
development of phosphate crystals)
1. PRESENT COMPLAINT
1. HPC
1. PHYSICAL EXAMINATION
1. LABS
1.
1. ACUTE TUBULAR NECROSIS
2.PRESENT COMPLAINT
2. HPC
2. PE
2. LABS
2. IMAGING
2.
2. ADULT POLYCYSTIC KIDNEY DISEASE