HDP400: Human Disease
Process II
Professor Joe Gordon
Room 107
Extension: 5240
email: [email protected]
What you need to know
Breakdown:
In-class Quizzes
20%
Test #1
20%
Test #2
25%
Test #3
15%
Test #4
20%
100%
Resources:
1) Text Books – Copstead
2) Blackboard site (http://my.senecacollege.ca)
3) Library/Resource Centre
References and Other Sources
1)
Marieb EN. Human anatomy and physiology, 5th Ed. San Francisco, CA: Addison Wesley Longman
Inc. (2001).
2)
Marieb EN. Essentials of human anatomy and physiology, 6th Ed. San Francisco, CA: Addison Wesley
Longman Inc. (2000).
3)
Gould BE. Pathophysiology for the health-related professions. Philadelphia, PA; W.B. Saunders
Company (1997).
4)
Porth CM. Pathophysiology: concepts of altered health states, 5th ed. Philadelphia, PA: LippincottRaven Publishers (1998).
5)
Lewis SM, Heitkemper MM, Dirksen SR. Medical-Surgical Nursing, 5th. St. Louis, MS: Mosby, Inc.
(2000).
6)
Ganong WF. Review of medical physiology, 19th Ed. Stamford, Connecticut: Appleton and Lange
(1999).
7)
Ingraham JL, Ingraham CA. Introduction to microbiology, 2nd. Pacific Grove, CA: Brooks/Cole. (2000).
8)
McPhee SJ, Lingappa VR, Ganong WF, Lange JD. Pathophysiology of Disease, 3rd. New York, NY:
McGraw-Hill Co. (2000).
9)
Atlas of pathophysiology. Springhouse, PA: Springhouse Corp. (2002).
10)
Bear MF, Connors BW, Paradiso MA. Neuroscience: exploring the brain. Media, PA: Williams and
Wilkins (1996).
11)
Lodish H, Baltimore D, Berk A, Zipursky SL, Matsudaira P, Darnell J. Molecular Cell Biology, 3rd Ed.
New York, NY: Scientific American Books (1995).
Urinary System
The major roles of the kidneys are to:
1) Filter metabolic wastes from the blood (eg. Urea, uric acid, and creatinine)
and excrete them from the body in the urine.
2) Regulate the blood volume and blood pressure by altering the volume of
urine produced, and by releasing the enzyme renin into the blood, which
activates angiotensin II promoting vasoconstriction and aldosterone
secretion.
3) Production of erythropoietin in response to low blood O2 levels.
Erythropoietin stimulates erythrocyte proliferation and maturation in the
bone marrow.
4) Regulate the amount of electrolytes (ie. Na+, K+, Cl-, Ca++, phosphate) in
the blood and extracellular fluid by altering the urine concentration and
composition. In addition, the kidneys are responsible for activating vitamin
D, which promotes Ca++ absorption in the small intestine.
5) Regulate the body’s pH by controlling the amount of H+ secreted and
HCO3- reabsorbed from the filtrate.
Anatomy of the Urinary System
• The kidneys lie towards
the posterior surface, and
are partially protected by
the lower ribs.
• The kidneys receive
blood from the renal
arteries, which branch
directly from the aorta, and
return their ‘cleansed’
blood to the inferior vena
cava through the renal
veins.
• Urine produced in the
kidneys travels down the
ureters to the urinary
bladder for storage.
• Urine leaves the body
through the urethra during
contraction of the bladder.
(2)
Anatomy of the Urinary System Continued
(1)
• The kidneys are located posterior to the peritoneum (ie. The connective tissue
surrounding the GI tract) in the retroperitoneal area.
• Each kidney is covered by a fibrous capsule and a layer of adipose tissue.
• Because there are no pain receptors within the kidney, pain is only present
when there is impingement on the renal capsule or ureter.
The Kidney
• Blood enters the kidney and is
transported by smaller arteries to
the outer portion of the kidney,
called the cortex. The majority of
blood is filtered here.
• The inner portion of the kidney,
called the medulla, alters the
composition of the filtrate and forms
urine. This area is susceptible to
ischemic damage since it is very
metabolically active, yet has a low
O2 tension. The medulla is
arranged in triangular shaped
structures called medullary
pyramids.
• The urine drains into collecting
ducts in the medulla and eventually
passes to the renal pelvis and into
the ureters for transport to the
urinary bladder.
(2)
The Nephron
• The urine producing apparatus in
the kidney is called the nephron.
• The nephron consists of a
glomerulus, that filters the blood and
forms a filtrate, and a tubule, that
converts the filtrate into urine by
reabsorbing water and electrolytes
from the filtrate.
• The tubule has three distinct
regions. 1) The proximal tubule; 2) the
loop of Henle, which enters into the
medulla of the kidney; and 3) the
distal tubule.
• The distal tubule drains into a
common collecting duct that makes
some final modifications to the urine
and ultimately transports the urine
into the ureters.
(1)
Blood Supply to the Nephron
• Blood flows into the
glomerulus through the
afferent arteriole, which
divides into the glomerular
capillaries.
• These capillaries are very
porous and allow large
amounts of blood plasma to
filter out into the glomerular
capsule and into the
proximal tubule.
• Blood leaves the
glomerulus through the
efferent arteriole, which
divides into the peritubular
capillaries. These capillaries
surround the tubule and
function to absorb water and
electrolytes from the filtrate.
(1)
Renal Blood Pressures
(1)
• Blood to the kidney is regulated to maintain filtration, and not to satisfy the metabolic
needs of the tissue. At rest the kidneys receive 25% of the cardiac output (1.3 L/min).
These numbers are decreased with exercise and exertion.
•The blood pressure in the glomerular capillaries is about 55 mmHg. This high
pressure is maintained by the flow through the afferent arteriole (BFG) and the high
resistance to flow in the efferent arteriole (RG). The glomerular blood pressure (BPG) is
the driving force to create filtration, and determined by:
BPG = BFG x RG
Where, BFG is increased with afferent arteriolar dilation and decreased with
constriction, and RG is increased with efferent constriction and decreased with dilation.
When BPG is increased, filtration is increased, and when BPG is decreased, filtration is
decreased.
Urine Formation
The nephron uses 3 processes to
produce urine and control its
volume and composition:
1) Filtration: Water and dissolved
solutes smaller than 8 nm are
filtered through the glomerular
capillaries and into the tubule.
2) Reabsorption: Water, glucose,
amino acids and selected
electrolytes are transported
into the tubular cells an enter
into the peritubular capillary
blood.
3) Secretion: H+, K+, some
metabolic wastes and drugs
are secreted from the tubular
cells into the filtrate.
(2)
The Glomerulus
(1)
• The glomerular
capillaries are formed
from the afferent arteriole.
• Like most capillaries,
the glomerular capillaries
are comprised of
endothelial cells;
however, these cells have
‘holes’ called
fenestrations and are
covered by epithelial cells
call podocytes.
• The glomerular capillaries are surrounded by Bowman’s capsule, which is
continuous with the renal tubule.
• Associated with the afferent and efferent arterioles is the juxtaglomerular
apparatus. The juxtaglomerular cells secrete renin in response to low blood
pressure or SNS stimulation. The macula densa is part of the distal tubule and
senses changes in the concentration of the filtrate, and can dilate or constrict
the arterioles appropriately.
The Glomerulus Continued
• The fenestrations in the glomerular
capillaries only allow particles less than 8
nm to pass; however, the capillary basement
membrane contains negatively charged
proteoglycan. This effectively repels other
anions, like the protein albumin.
• The glomerulus is commonly injured by
immune complexes (ie. Antibody-antigen
complexes). This produces an inflammatory
response in an attempt to destroy the
immune complex by phagocytosis.
(1)
• If the immune complexes are within the endothelial layer, they are accessible
to phagocytes. This is common in nephritic syndrome. If the immune complexes
lie within the epithelial cells (ie. On the other side of the basement membrane)
they are not accessible to phagocytes and this creates nephrotic syndrome.
• Inflammation of the glomerulus allows protein to enter the filtrate and urine;
however, in nephritic syndromes there are blood cells in the urine and in
nephrotic syndromes there are not.
The Glomerular Filtration Rate
• Filtration through the glomerular
capillaries is governed by the
same forces as any other capillary
in the body. Blood hydrostatic
pressure pushes fluid out and the
colloid osmotic pressure pushes
fluid into the capillary.
(1)
• The glomerular capillaries are
fenestrated to increases their
permeability, also the blood
pressure is quite high compared
to other capillaries.
• The glomerular filtration rate (GFR) is the amount of blood plasma filtered
through the capillaries in one minute (125 mL/min). GFR is regulated primarily
by altering the glomerular blood pressure (BPG). Increasing flow through the
capillaries (ie. Afferent dilation) and increasing the resistance to flow (ie.
Efferent constriction) increases GFR; whereas, decreasing flow and
decreasing resistance decreases GFR.
Regulating GFR
(1)
The Renal Tubule
(2)
• The renal tubule is
responsible for
reabsorbing glucose,
amino acids,
electrolytes and water
from the filtrate.
• Other substance (ie. K
+) may be secreted into
the filtrate.
• Reabsorption and
secretion may occur
passively or by active
processes.
• Passive processes include diffusion and osmosis; whereas, active processes
require ATP either directly (primary active) or indirectly (secondary active or cotransport).
• 180 L/day of water is filtered through the glomerulus and the normal urine
volume is only about 1 L/day. Therefore, more than 99% of the filtrate is
normally reabsorbed.
The Proximal Tubule
(1)
• Most reabsorption in the
proximal tubule occurs by
Na+ co-transport.
• A Na+ concentration
gradient is created by the
Na+/K+ pump on the basal
surface of the tubule cells.
This gradient is used to
power the absorption of
other molecules like
glucose.
• The glucose transporter is called the sodium-dependent glucose transporter
(SGLT).
• Cl- ions diffuse passively through Cl- channels and maintain electrochemical
neutrality.
• Water is reabsorbed by the osmotic gradient created by reabsorption of
solutes. Water passes the plasma membrane through pores created from the
protein aquaporin-1.
The Loop of Henle
• The primary function of the loop
of Henle is to remove water from
the filtrate.
• This is achieved by a highly
concentrated interstitial fluid
(ISF) that becomes more
concentrated deeper into the
medullary pyramid. This
concentration gradient is
maintained by the peritubular
capillaries.
• As filtrate descends into the
loop, water is pulled out by
osmosis because of the ISF
concentration.
(1)
• The loss of water creates a highly concentrated filtrate. As the filtrate ascends
the loop, Na+ and Cl- are actively reabsorbed to reduce the filtrate
concentration.
• The net result is a greatly diminished filtrate volume.
Aldosterone and Vasopressin
(Antidiuretic Hormone)
Tubule
Lumen
Tubule
Epithelial
cell
• Both aldosterone and vasopressin
(ADH) exert the majority of their effects
on the collecting ducts of the kidneys.
• Released from the adrenal cortex in
response to angiotensin II, aldosterone
increases the production of the
epithelial sodium channel (ENaC). This
increases the sodium absorption from
the collecting duct. Water follows
osmotically through aquaporin-1.
• ADH is released from the posterior
pituitary in response to high
extracellular fluid osmolarity or low
blood pressure. ADH causes a vesicle
bound aquaporin-2 to move to the
plasma membrane and increase the
absorption of water.
Interstitial
fluid
Aldosterone
Na+
+
K+
K+
Na+
H 2O
ADH
+
H 2O
Renal Control of Acid-Base Status
(1)
• The proximal tubule cells utilize the
enzyme carbonic anhydrase to help
regulate the body’s pH.
• This enzyme converts CO2 and H2O
into H+ and HCO3-, and vise versa.
• CO2 from the peritubular capillaries
or from filtered HCO3- is converted into
H+ and HCO3- within the cells.
• H+ is then secreted into the filtrate
through the Na+/ H+ exchanger, while
HCO3- is reabsorbed.
• This system is regulated by the
PCO2 in the peritubular capillaries.
• If PCO2 is elevated, more H+ is secreted and HCO3- absorbed. Additionally,
K+ tends to be conserved when more H+ is secreted. If PCO2 is decreased,
less H+ is secreted and HCO3- absorbed.
• H+ secretion and HCO3- absorption are therefore intimately linked.
Metabolic Acidosis
(3)
Normal Values:
pH = 7.4
HCO3- = 24 mmol/L
H2CO3 = 1.2 mmol/L
Ratio = 20:1
PCO2 = 40 mmHg
• Renal disorders can result in failure of the tubules to secrete H+ and reabsorb
bicarbonate. This results in a metabolic acidosis.
• Bicarbonate is reduced and the normal 20:1 is depressed to about 18:1 due
to a bicarbonate level less than 24 mM/L.
• The respiratory system has a limited ability to compensate for this by
increasing the respiratory rate. This effectively reduces the PCO2 to less than
40 mmHg and the H2CO3 to less than 1.2 mM/L, and restores the 20:1 ratio.
• If persistent, the compensation is insufficient and decompensation results.
Renal Disorders
Renal disorders commonly manifest as elevated blood urea nitrogen (BUN),
elevated serum creatinine, and failure to maintain Na+, K+, water, and acidbase balance. These manifestations can result in complications such as
hypertension, symptoms of CHF, peripheral edema, and death.
Azotemia: When metabolic products that are normally excreted by the kidneys
accumulate in the blood. Examples include urea, creatinine, and other
toxic metabolic products.
Uremia: A complex group of symptoms that occur due to inadequate renal
function. Can be caused by accumulating metabolic toxins, fluid and
electrolyte imbalances, acidosis, and anemia.
Oliguria and anuria: Oliguria is a diminished urine volume; whereas, anuria is
an absence of urine production.
Diuresis or polyuria: Increased urine production.
Renal disease can be categorized by the site of the lesion (eg. Glomerulus vs.
tubule), by the etiology (eg. Immumologic, infectious, hemodynamic, etc.),
or a combination of the two (eg. Prerenal, intrarenal, and postrenal).
1) Prerenal Disease: Results from inadequate blood flow to the nephron.
Examples include hypovolemia, hypotension, drug-induced reduction in
perfusion, septic shock, and stenosis of the renal arteries.
Renal Disorders Continued
2) Intrarenal Disease: Result from intrinsic damage to the nephron.
Examples include acute tubular necrosis, glomerulonephritis, nephrotic
syndrome, vasculitis, malignant hypertension, diabetic nephropathy, and
pyelonephritis.
3) Postrenal Disease: Result from urinary tract obstruction. Examples
include ureter obstruction, prostate disease, malignancy, and calculi.
Renal failure can be managed by attempting to treat the cause, conservative
dietary manipulation, dialysis, and renal transplant. If anemia is present,
erythropoietin is used to stimulate bone marrow production of red blood
cells. If inflammation is present, corticosteroids are often used.
Acute Renal Failure
• Acute renal failure (ARF) represents a group
of disorders that cause in rapid deterioration in
renal function resulting in azotemia.
• ARF presents as rapidly rising BUN/
creatinine and a diminished urine volume (ie.
oliguria).
• Sepsis is one of the most common causes of
ARF. In addition to hypotension caused by
systemic vasodilation, and patients with
sepsis are often exposed to nephrotoxic
antibiotics.
• Patients with preexisting renal hypoperfusion
(ie. CHF, diabetes, renal stenosis) may
develop ARF by ingesting NSAIDs or ACE
inhibitors, as prostaglandins dilate the afferent
arteriole and angiotensin II acts to constrict
the efferent arteriole.
(4)
• Other causes include eclampsia, hemolysis, and muscle damage due to
trauma (ie. Hypermyoglobinemia/rhabdomyolysis), as filtered heme-containing
molecules damage the renal tubules.
Acute Renal Failure Continued
• In the early stages of prerenal disease,
GFR is decreased due to renal
hypoperfussion (ie. Prerenal azotemia).
• Regardless of the etiology, ARF will
likely result in necrotic death of the
tubule epithelial cells (ie. acute tubular
necrosis) without successful treatment.
• Manifestations of ARF are a result of
tubule obstruction by necrotic tissue.
This increases the intratubule pressure
and offsets the filtration pressure. The
result is a dramatic reduction in GFR.
• Acute tubular necrosis results in a loss
of tubular function and failure to
concentrate urine.
• Cell debris and protein can be formed
to together within the tubule to forms
casts, which are excreted in the urine.
(3)
Acute Tubular Necrosis
(9)
Manifestations of ARF
Initial signs/symptoms include:
1) Elevated BUN and creatinine (ie. azotemia) because of decreased GFR.
BUN increases rapidly with increased protein catabolism (eg. Fever and
sepsis). Creatinine is unusually high if rhabdomyolysis is the cause.
2) Oliguria caused by decreased GFR and/or tubule obstruction. However,
roughly 25% of patients will not have oliguria, especially when ARF is
caused by nephrotoxins.
3) Hyperkalemia occurs if GFR is greatly reduced and there is significant
acidosis. Typical ECG changes can occur and predispose to arrhythmias.
4) Fatigue and malaise likely due to water intoxication (ie. Hyponatriemia),
hyperkalemia, acidosis, and elevated metabolic wastes (ie. Toxicity).
Later symptoms include:
1) Dyspnea, orthopnea, rales, and third heart sound caused by fluid overload.
2) Edema caused by fluid overload.
3) Altered mental status occurs when metabolic wastes become increasingly
elevated in the blood. Although elevated BUN is not toxic itself, it is a good
indicator toxicity. Altered electrolytes and acidosis contribute.
4) Urinalysis may show hematuria, proteinuria, and pyuria. With acute tubular
necrosis cast are present and the urine is very dilute (low specific gravity).
Mortality rates and Resolution
• Since ARF commonly affects people with serious illness, mortality rates are
rather high, ranging from 42%-88% even with dialysis. Immunosuppression
and bleeding can occur because of toxicity, and often contribute to mortality.
• ARF is potentially reversible even when complicated by tubule necrosis,
since these cells are epithelial. Most patients who recover will eventually
regain a normal renal status; however, if the damage to the kidneys is
extensive, entire nephrons could be lost and chronic renal failure can ensue.
Therefore, prevention and early treatment must be emphasized to prevent
acute tubular necrosis whenever possible.
• Resolution of ARF is characterized by a phase of diuresis, which begins a
few days to weeks after the onset of azotemia and oliguria. Diuresis usually
begins before the nephrons have fully recovered; therefore, BUN and
electrolytes remain abnormal indicating decreased GFR and tubular
dysfunction. Careful monitoring to prevent fluid depletion and low
electrolytes is indicated.
• In ARF clearance of medication is often altered. Careful monitoring for
signs of drug toxicity must be done during the oliguric and diuretic phases.
Chronic Renal Failure
• Chronic renal failure results from the
gradual irreversible destruction of nephrons
and loss of renal function.
• This results in an increased workload on the
remaining nephrons, increased glomerular
filtration pressure, and hyperfiltration.
(8)
• Hyperfiltration predisposes to fibrosis and scaring (glomerulosclerosis) and
increases the rate of nephron destruction.
• End-stage renal failure presents as a complex of symptoms called uremia.
Uremia is caused by retained fluid, electrolytes, waste products and
hormones, and loss of renal endocrine function. Additionally, BMR is reduced
(hypothermia) and blood lipoproteins are increased (probably due to
decreased Na+/K+ ATPase activity and lipoprotein lipase activity).
• Uremia produces clinical abnormalities in fluid and electrolyte balance, bone
metabolism, CNS, cardiovascular, skin, GI, hematologic, and metabolic
control.
Chronic Renal Failure Continued
Occurs in three stages:
1) Reduced renal reserve: Up
to 50% of nephrons can be
lost without producing signs
and symptoms. However, if
the cause is not detected,
damage will continue.
2) Renal insufficiency: Occurs
when more than 20% of
nephrons remain. There is
a decrease in GFR,
reabsorption and secretion
capacity, resulting in
moderate azotemia (ie. Elevated BUN).
(3)
3) End-stage renal failure (uremia): Occurs when less than 20% of nephrons
remain. GFR and tubular function are greatly reduced resulting in oliguria/
anuria, marked azotemia, and failure to concentrate urine.
Manifestations of Renal Insufficiency
The manifestations of this stage are predominately due to decreased GRF,
and hyperfiltration of remaining nephrons.
1) Hyponatriemia and hypokalemia.
2) Mild azotemia: Due to decreased GFR.
3) Mild acidosis: Due to decreased tubular function resulting in diminished
H+ secretion and HCO3- reabsorption.
4) Generalized weakness and fatigue: Likely due to azotemia, mild
acidosis, electrolyte abnormalities, and possibly mild anemia
(decreased erythropoietin production).
5) Increased blood pressure: Falling renal perfusion stimulates the
overproduction of renin, increasing systemic vasoconstriction and
aldosterone secretion.
* Any condition that increases H+, decreases body fluid, or alters
electrolytes will induce uremic symptoms. Examples include vomiting,
diarrhea, infection, diminished respiration, stress, dehydration,
increased catabolism or nephrotoxic drugs.
Manifestations of Uremia
1) Fluid, Na+, and K+: Sodium and volume overload are
common in uremia. Excess ingestion of sodium contributes
to circulatory congestion, hypertension, ascites, edema, and
weight gain. Excess water can causes hyponatriema. There
is also a diminished reserve to conserve sodium and water
in the during time of loss (ie. Vomiting and diarrhea). This
can lead to circulatory shock. Hyperkalemia can become a
serious problem is GFR falls below 5 mL/min. Hemolysis,
acidosis, and infection increase the risk of hyperkalemia.
2) Metabolic acidosis: Occurs only moderately when GFR is
↓ Vitamin D
greater than 20 mL/min, which can be compensated by
increased respirations. Will become decompensated if GFR
falls below 20 mL/min or if exposed to other acid loads (ie.
↓ Blood Ca++
Lactic acidosis, infection or pneumonia).
3) Bone and Mineral: Decreased activation of Vitamin D results
↑ PTH
in decreased absorption of calcium from the gut, and a fall
secretion
in serum calcium levels. This stimulates PTH secretion and
bone breakdown in an attempt to raise serum calcium.
Chronic acidosis also contribute to bone breakdown.
↑ Bone
Calcifications occur due to increased Ca2+ x phosphate.
breakdown
Manifestations of Uremia Continued
4) Cardiovascular and Pulmonary: Symptoms of circulatory congestion,
hypertension, and pulmonary edema occur because of sodium and
volume overload, and hyperreninemia. Irritation by uremic toxins can
cause pericarditis. Atherosclerosis is accelerated resulting in MI, stroke,
and PVD. This is mostly due to elevations in blood pressure and
hyperlipidemia caused by inhibition of lipoprotein lipase.
5) Hematological: Decreased production of erythropoietin causes anemia
with hematocrits of 20-25%. This is not corrected by dialysis, and requires
erythropoietin treatment. Abnormal hemostasis and white cell function are
also common in uremia, resulting in bleeding and immunosuppression.
6) Neurological: Symptoms include sleep disorders, poor concentration, loss
of memory, seizures, hiccups, twitching, and coma. Sensory peripheral
neuropathy can also occur. Neurological effects were believed to be due
to urea; however, it is likely that they are caused by elevated organic
acids or phenols, mostly derived from protein catabolism (ie. Protein
restricted diet). BUN corresponds well with the degree of CNS
disturbance.
7) GI and skin: Common findings include anorexia, nausea, and vomiting.
Bad breath (uremic fetor) can occur when saliva enzymes breakdown
urea into ammonium. Skin changes include uremic frost and colour.
Diabetic Nephropathy
• Diabetes is the leading cause of end-stage chronic renal failure requiring
dialysis and transplant.
• Diabetic nephropathy primarily involves the glomerular capillaries. In the early
stages, loss of negatively charged proteoglycan in the basement membrane
allows small amounts of albumin to filter into the tubules and enter the urine
(ie. Microalbuminuria).
• Fibrosis and thickening of the capillary basement membrane occurs, and is
referred to as glomerulosclerosis. As this process continues, the glomerulus is
destroyed, an inflammatory response is initiated, and the nephron is lost.
• This results in an increased workload on the remaining nephrons, and
hyperfiltration to maintain GFR. Hyperfiltration predisposes to more
glomerulosclerosis and increases the rate of nephron destruction. As the
number of glomerular lesions increase, massive proteinuria occurs.
• Eventually, the loss of nephrons is so great that renal failure occurs.
Hypertension increases glomerular hyperfiltration and can accelerate nephron
loss. Type II diabetics often have hypertension at the time of diagnosis, but
type Is usually do not develop hypertension until after the onset of
nephropathy. Nephropathy occurs in 25% of type Is, but only 5% of type IIs.
Urinary Tract Infections
• UTIs are the second most
common infections seen by health
care providers.
• Lower UTIs include cystitis
(bladder) urethritis (urethra);
whereas, upper UTIs involve the
kidney, and are called
pyelonephritis.
• Most UTIs are ascending and
arise from microbes entering the
urethra; however, some causes of
pyelonephritis are blood-borne.
• The major host defense against
ascending infection is the
‘flushing’ effect of urine flow.
(3)
Therefore, stasis of urine is a major contributing factor causing UTI.
• An Escherichia Coli opportunist infection is the most common cause of UTI,
including nosocomial infections. Fecal proteus bacteria are second.
Etiology of UTI
• E. coli’s ability to cause UTIs is related
to its pili and ability to bind to urinary
epithelial cells. Urine flow tends to
prevent this. Some bacterial strains can
use urea as an energy source, liberating
free ammonium (eg. Proteus).
Glucosuria (eg. Diabetes) provides an
additional energy source.
(7)
• Females are generally more susceptible to UTIs due to anatomical
vulnerability (eg. Short, wide urethra, and proximity to the anus). However,
older males often suffer from prostate hypertrophy which causes retention of
urine and frequent UTIs.
• Other factors that predispose to UTIs are incomplete bladder emptying and
obstruction of urine flow. Examples include incontinence, pregnancy, scar
tissue, congential defects of the ureter, or impaired blood supply to the bladder.
Catheterization and sexual intercourse also increases the risk of UTI.
• A relationship exists between UTIs and renal calculi. Calculi can obstruct
urine, causing infections, while ammonium liberated by infection makes the
urine more alkaline and predisposes to calculi formation.
Cystitis
Manifestations:
1) Pain: Abdominal pain and
pain during micturition
(dysuria) are common in
cystitis.
2) Frequency and urgency
(Irritative symptoms):
Inflammation and swelling of
the bladder reduce its
capacity often resulting in
frequent and urgent urination.
(9)
3) Systemic signs of infection (ie. Fever, malaise, nausea, and leukocytosis).
4) Urinalysis: Bacteriuria, pyuria, and microscopic hematuria are common
creating cloudy urine with an unusual odor.
Treatment:
•
Antibiotic therapy combined with increased fluid intake help eliminate
evading organisms. Cranberry and blueberry juice contain tannins that
interfere with the pili of E. coli and prevent binding to urinary epithelia.
Pyelonephritis
• Pyelonephritis can result from
an ascending infection from the
bladder or from bacteriemia.
• Often the infection involves the
renal pelvis and medullary
tissue, resulting in inflammation
and possibly necrosis.
• If severe, exudate and pus
compress the renal vessels
resulting in ischemia and
hypertension, while compression
of the ureter obstructs urine flow.
(9)
Manifestations:
• Pain associated with distension of the renal capsule is described as dull
aching in the lower back or flank area. Systemic signs are marked with
symptoms of cystitis (ie. Dysuria). Urinalysis includes casts (leukocyte and
epithelia), failure to concentrate the urine, and bacteriuria similar to cystitis.
Bilateral obstruction is likely to cause acute renal failure. Chronic or repeat
infection can lead to chronic failure.
Glomerulonephritis
Glomerulonephritis can be classified according to the clinical presentation,
which can be nephritic syndrome or nephrotic syndrome. They are caused
by disorders of the kidney or systemic diseases that affect the kidney.
Nearly all causes are immune mediated. Most common include: postinfectious disease (eg. Streptococci, pneumococci, hepatitis B,
mononucleosis, measles, mumps, malaria), sepsis, endocarditis, lupus,
rheumatic disease, and idiopahtic autoimmune.
The common clinical presentation of nephritic syndrome involves hematuria,
proteinuria, reduced GFR, and hypertension. However, nephritic
syndrome generally follows one of three paths:
1) Acute glomerulonephritis: An abrupt onset of symptoms, often resulting in
acute renal failure, followed by full recovery of renal function.
2) Rapidly progressive glomerulonephritis: An abrupt onset of symptoms, in
which recovery from acute renal failure does not occur. Over weeks to
months this disorder progresses to chronic renal failure.
3) Chronic glomerulonephritis: Acute glomerulonephritis which progresses
slowly over a period of years (ie. 5-20) to chronic renal failure.
* It is unclear why nephritic syndromes can take alternatives courses
Acute Poststreptococcal Glomerulonephritis
• APSGN occurs because of an immune
attack on a streptococcal antigen results in
immune complex and complement deposits
in the glomerular capillaries.
• Nephritic manifestations usually occur
7-10 days after the onset of a pharyngeal or
cutaneous infection with group A
streptococcus (ie. Streptococcal pyogens),
and resolve over a period of weeks.
• APSGN usually effects children between
ages 3-7 years, and is more common in
boys.
Manifestations:
• Damage to the glomerular capillaries gives
rise to hematuria and proteinuria.
• Glomerular infiltration with inflammatory
cells results in a fall in GFR, causing
oliguria and azotemia.
(4)
APSGN Manifestations Continued
• Pain in the flank or lower back is attributed
to distension of the renal capsule.
• Hypertension and edema (ie. Typically facial
and periorbital) are a consequence of fluid
and salt overload due to a reduced GFR.
Hyperreninemia and decreased colloid
osmotic pressure may also contribute.
• Blood analysis reveals an elevation of
antibodies to streptococcal antigens (ie.
Antistreptolysin O; ASO, and
antistreptokinase; ASK). Metabolic acidosis
may also be present.
• Urine analysis reveals proteinuria,
hematuria, and erythrocyte casts.
Resolution:
• Most cases resolve with a diuretic phase
after treatment for the infection (ie. Especially
in children). In adults, it may not be as easily
resolved. Some cases ultimately progress to
chronic renal failure.
(3)
Nephrotic Syndrome
• Nephrotic syndrome occurs
secondary to a number of disorders
including infection, lupus, exposure
to nephrotoxins, neoplasia, diabetic
nephropathy, and immune-mediated.
• This syndrome commonly presents
with marked proteinuria,
hypoalbuminemia, generalized
edema, hyperlipidemia, and lipid in
the urine (milky appearance with
increased specific gravity).
(3)
• Nephrotic syndrome results from inflammation of the glomerulus with
immune complexes within the glomerular basement membrane or foot
processes, but without the presence of cellular immune cells.
• Reduced colloid osmotic pressure results in massive edema in dependent
areas, ascites, weight gain and effusions. Blood pressure is not usually
elevated due to third-spacing and hypovolemia. Hypovolemia can manifest
as syncope, circulatory shock, and acute renal failure. Impaired capillary
exchange may cause skin breakdown and infection.
Nephrotic Syndrome Continued
• Hyperlipidemia appears to result from the decreased colloid osmotic
pressure. This stimulates the liver to increase production of lipoproteins,
resulting in elevated plasma LDL and VLDL.
• Loss of plasma proteins other than albumin can cause : deficient
phagocytosis and opsonization (loss of antibodies and complement),
hypercoagulability (loss of plasma anticoagulants like antithrombin),
secondary parathyroidism (loss of vitamin D binding proteins), iron
deficiency (loss of transferrin) and abnormal thyroid function (loss of thyroid
binding protein).
• Some cases of nephrotic syndrome are considered a minimal change
disease, where all manifestations are due to proteinuria and progression to
uremia does not occur.
• Sometimes the distinction between nephrotic and nephritic forms of
glomerulonephritis is difficult or impossible to make.
Treatment:
• Usually treated with glucocorticoids to reduce glomerular inflammation.
Reoccurrence is common.
Urinary Calculi
•
The most common cause of
urinary tract obstruction is
urinary calculi or nephrolithiasis
•
Stones can be made of various
solutes the kidney normally
excretes. Stone formation
requires a nucleus to initiate
formation and an environment
that encourages precipitation
•
There are generally four types of
stones that can form in the
urinary tract.
1) Calcium (phosphate or oxalate)
2) Struvite (magnesium,
ammonium, and phosphate)
3) Uric acid
4) Cystine
(9)
Urinary Calculi Continued
• Approximately 75% of all stones contain calcium, and most are due to
idiopathic hypercalciuria. Other causes include hyperparathyroidism, and
immobility.
• Uric acid stones account for 10% of stones with hyperuricosuria, gout,
chemotherapy, obesity, a diet high in organ meats, red meat, and acidic urine
acting as contributing factors.
• Struvite stones represent nearly 15% of stones. They occur primarily because
of a chronic or recurrent UTI with urea metabolizing bacteria where the urine
pH is alkaline. Cell debris may also act as a nucleus for stone formation.
• Cystine stone are very rare. They usually result from inherited disorders of
amino acid metabolism
Pathogenesis:
• Renal stones occur when organic salts precipitate in the urinary tract. This
can result from saturation (ie. Too much solute, not enough solvent), or due to
a change in the solubility of a salt (ie. Change in pH).
• Dehydration favours stone formation by increasing urine concentration and
decreasing the Ca++ transit time. High Na+ and high protein diets; as well as
hypertension also predispose to stone formation.
Manifestations of Urinary Calculi
• Impingement of the renal capsule results in lower back and flank pain;
whereas distension of the ureter causes the pain to radiate into the groin,
perineum, or scrotum. This acute, intermittent, excruciating pain is often called
renal colic. As the stone moves into the bladder and urethra, lower abdominal
pain occurs.
• Oliguria, hematuria occur with and without fever. If stones obstruct both
kidneys, there is underlying renal disease, or if the patient has only one
kidney, post-renal azotemia (ie. acute renal failure) and anuria result. Other
signs of hydronephrosis and hydroureter may occur.
Treatment:
• Passage of a stone usually requires fluids, bed rest, and analgesics.
Occasionally, diuretics, antibiotics, alkali therapy, or aggressive stone removal
is required. If possible, a sample of the stone should be kept to identify the
underlying pathophysiology and prevent reoccurrence. Alterations in diet are
often useful. Low sodium and protein intake often prevents stone formation,
while decreasing calcium intake is only helpful a few sufferers. In others,
diminished calcium intake may accelerate stone formation. A reduction of
dietary organ meats, red meat, and caffeine is useful for uric acid stones.
Supplementation of citrate magnesium, and dietary fibre is also useful.
Urinary Obstruction
• Renal calculi and prostate disease are the
more common causes of urinary obstruction.
• The two most damaging effects of obstruction
are stasis of urine, which predisposes to
infection, and increased backpressure, which
can impair renal blood flow and damage renal
tissue. Obstruction can be either partial or
complete.
• Impedance to urinary flow increases the pressure
within the renal pelvis and calices. This can obstruct
blood flow to the medulla and cause ischemic damage
and necrosis.
• Irreversible nephron damage can occur within a few
days of complete obstruction; whereas, recovery can
take weeks after the obstruction is removed.
• Dilation of the ureters (ie. Hydroureter) and renal
pelvis (ie. Hydronephrosis) occurs with prolonged
obstruction.
(4)
Urinary Obstruction Continued
• Renal colic occurs due to
distention of the bladder, ureter,
or renal capsule. Pain is usually
more severe in acute
obstructions.
• A disruption of visceral
innervation may impair GI
mobility causing abdominal
distension and paralytic ileus.
• Early diagnosis and treatment
is important because failure to
restore urinary flow can result in
permanent renal damage. A
bilateral obstruction can result in
renal failure.
(9)
Benign Prostate Hyperplasia
• BPH is nonmalignant growth of
prostate.
Testosterone
• The cause is unknown; however,
aging and hormonal factors play a
role.
• As the name suggests, the growth
of the prostate is related to increased
cell number and not increased cell
size (ie. Hypertrophy).
• BPH effects 40% of men in their
fifties, 70% in their sixties, and 90%
in their eighties. One-third of men
over 65 are symptomatic.
Estrogen +
Growth
Factors
• The normal prostate contains both epithelial and smooth muscle cells.
Circulating testosterone acts to produce protein growth factors (eg. FGF, IGF)
that act to maintain normal prostate size. Even though serum testosterone
decreases as the male ages, serum estrogens tend to rise. Estrogens increase
the number of testosterone receptors and increase prostate sensitivity.
Prostate smooth muscle contains α1- receptors that stimulate them to contract.
Manifestations of BPH
Obstruction to urine outflow and bladder dysfunction are responsible for the
major manifestation.
Symptoms fall into two categories. Irritative symptoms and obstructive
symptoms.
1) Irritative symptoms are a result of bladder hypertrophy and dysfunction.
They include: frequency, nocturia, and urgency.
2) Obstructive symptoms result from narrowing of the bladder neck and
urethra. They include difficulty initiating urination, decreased urinary flow
(ie. Force and caliber), intermittency, hesitancy, and dribbling.
•
Complications include urinary tract infections, hematuria, post-renal
azotemia, and chronic renal failure from bilateral hydroureter and
hydronephrosis.
•
Digital rectal exam usually reveals diffuse enlargement of the prostate
that does not correlate well with symptoms. Bladder distention and
hypertrophy is also common.
Treatment: Usually involves α1-blockers, androgen-blockade, prostate stents,
and surgery.
Prostate Cancer
• In 2008, prostate cancer was the most common cancer in males, and was
third in number of cancer deaths. The mortality rate is estimated at 15-20%.
• The cause of prostate cancer is unknown, although environmental and
genetic factors may play a role.
Risk factors: Men who have a first-degree and second-degree relative with
prostate cancer are at eight times the risk. Prostate cancer is more common in
men over the age of 50, but occurs earlier in men of African descent. It is
interesting that prostate cancer never develops in men who have been
castrated; therefore testosterone is believed to be a risk factor. Dietary fat and
red meat are believed to increase the risk, as well as obesity and inactivity.
There is no epidemiological data linking BPH or infectious disease to prostate
cancer; however, prostatitis may be a risk factor.
Manifestations:
• Most tumors are asymptomatic. Depending on the size of the tumor, there
may be changes in urination similar to BPH.
• The prostate produces a protein called prostate-specific antigen (PSA).
Although its function is not known, PSA can become elevated in the serum
during prostate disease (ie. Cancer, BPH and prostatitis).
Prostate Cancer Continued
• Since most prostate tumors are asymptomatic, screening is indicated for
those at risk. Common screening tests are serum PSA, rectal examination,
and ultrasound. Thirty percent of men with elevated PSA have prostate
cancer. Rectal exam can detect hard nodular tumors; whereas, ultrasound can
detect tumors are small as 5 mm.
• The diagnosis is usually confirmed with prostate biopsy.
Treatment:
• Prostate cancer is usually treated by surgery, radiotherapy, and androgendeprivation therapy.