Kidney and UI tract Flashcards
Every day, the kidneys filter ____L of blood to produce ____L of highly concentrated and specialized fluid called _____.
1700L
1L
Urine
3 main functions performed by the kidneys
Homeostasis
Elimination of drugs, toxins, poisons, and metabolic waste products from the blood
Hormonal Activity
How do the kidneys maintain homeostasis?
- Maintenance of proper serum electrolyte concentrations (e.g. Na).
- Maintenance of proper water balance.
- Regulation of the pH level in the blood.
- Regulation of blood pressure (through Na+ and water balance, renin production)
How do the kidneys maintain hormonal activity?
- Renin production to regulate blood pressure.
- Regulation of Vitamin D activity, by converting Vit. D precursors to a more active
form (affects calcium absorption / metabolism). - Release of a hormone, erythropoietin that stimulates red blood cell production in
the bone marrow
What is the Hilium of the kidneys and what enters this area
a concave middle aspect where blood vessels, nerves, and the urinary tract enter
What part of the kidneys does the renal cortex make up? What is located here and what takes place here?
Outer 1/3 of the kidney, glomerulis located here, filtration takes place here
What makes up the inner 2/3 of the kidney and what triangle shapes are located here?
Medulla, pyramids
What do the tips of the pyramids contain and what does this allow?
Opening of the collecting ducts, that empty urine into a sac-like space within the kidney called the
renal pelvis
Once emptied into the renal pelvis, where does urine travel
-urine is propelled from each kidney by rhythmic contractions along a 25 cm long
muscular tube, the ureter –> both ureters insert into the bladder –> the bladder empties at the base via another hollow muscular tube called the urethra
What is the difference in Urethras in men and women? What does this difference play a role in?
In men, the urethra is 20 cm long; in women, the urethra is 4 cm long
- this difference in urethra length plays a role in the higher incidence of urinary tract infection and urinary
incontinence in women
In men, where does the urethra pass through?
Prostate
What is a common problem in older men that leads to urinary obstruction?
Enlarged prostate
What is the main role of the kidney
to filter the blood
What is the functional filtration unit of the kidneys
a tuft of capillaries called the glomerulus
How many glomeruli does each kidney have
1 - 4 million
What is the glomerulus surrounded by
a double-walled capsule lined by epithelial cells called the Bowman’s capsule
What are the sieve-like holes in the capillaries of the glomerulus called and what do they allow
The capillaries of the glomerulus have
sieve-like holes (fenestrations) in their cytoplasm to allow easy passage of fluid from the
vascular space
What does the glomerular basement membrane (GBM) allow?
small molecules are allowed to pass through, while large serum proteins and other blood constituents are prevented from leaving the vessels
How is the glomerular basement membrane a selective molecular filter that acts both as a physical barrier and a charge barrier
The glomerular basement membrane is partly composed of negatively charged molecules, which repel negatively charged proteins in the blood such as albumin
What is a major cause of glomerular kidney disease
damage to the basement membrane
What is the final barrier that fluid must pass through on its way from the capillary space to the urinary
space
The epithelial cells that surround the capillaries. These cells or podocytes surround the capillaries with another mesh of finger-like processes
3 ways blood is filtered
- passing first through fenestrations in the capillary walls
- then the glomerular basement membrane,
- then the podocyte slit processes
The fluid that makes it through the glomerulus filter finds itself in the urinary space of the Bowman’s capsule. However, what must happened to it before it is excreted from the body? What would happen if it didn’t get concentrated?
It must be concentrated otherwise the body would become dehydrated and salt-depleted extremely
quickly
Where does the fluid enter when it exits the glomerulus? What is this area lined with?
Proximal convoluted tubule
-specialized epithelial cells that have re-absorptive and secretory properties
The proximal tubule actively reabsorbs about ___ of the filtered water and sodium, as
well as reabsorbing _______, _______, and various other substances
2/3
glucose, amino acids and other substances
The epethelial cells lining the loops of henle are responsible for establishing a __________ __________ in different parts of the kidney, which allows for resabsorption of ____ and ____. What mechanism is used to do this?
Concentration gradient
Water and ions
Active cellular pumping mechanisms
What are the pelvis, ureter and bladder lined by? what is this surrounded by?
They are all lined by multilayered epithelium of transitional cells (generally 5-7 cells thick), and surrounded by a layer of smooth muscle which has contractile properties
Can acute renal failure be reversible?
Yes if the underlying cause can be treated
Causes of acute renal failure? (3)
- Pre-renal / systemic (e.g. due to septic shock, dehydration, severe hemorrhage)
- Renal (e.g. drugs, toxins, infection, inflammation, ischemia -, acute tubular necrosis,
acute glomerulonephritis) - Post-renal (e.g. a urinary tract obstruction)
Chronic renal failure results in what?
progressive and irreversible destruction of kidney structures (e.g., glomeruli) and loss of function
Initial symptoms: chronic vs acute renal failure
While patients with acute renal failure present with rapid onset of symptoms, patients with chronic renal failure may be clinically silent at first
Conditions that may result in chronic renal failure
uncontrolled hypertension, chronic urinary tract
obstruction, disorders of the glomeruli, and systemic diseases such as, diabetes and systemic lupus erythematosus (SLE)
Causes of chronic renal failure
- Pre-renal (e.g. hypertension, diabetes, vasculitis)
- Renal (e.g. primary glomerular disease, chronic tubulointerstitial diseases)
- Post-renal (e.g. chronic urinary tract obstruction)
Problems associated with renal function decreasing below a critical level
- Edema
- Electrolyte disturbance
- Metabolic Acidosis
- Anemia
- Hypertension
- Bone disease
- Azotemia
Why does edema occur when renal function decreases below a critical level
- Loss of water regulation / salt balance.
- Serum proteins spilled into urine exacerbates the problem
Why does electrolyte disturbance occur when renal function decreases below a critical level
Inability to excrete excess electrolytes - increased levels of sodium, potassium, phosphate
Why does metabolic acidosis disturbance occur when renal function decreases below a critical level
Inability to regulate blood pH (lowered blood pH).
Why does anemia disturbance occur when renal function decreases below a critical level
Decreased erythropoietin synthesis - lack of red blood cell production
Why does hypertension disturbance occur when renal function decreases below a critical level
- sodium and water retention
- Increased renin production. Kidney releases renin in an attempt to improve blood flow by raising blood pressure. Renin helps regulate blood pressure.
Why does bone disease disturbance occur when renal function decreases below a critical level
- Increased blood phosphate + impaired tubular resorption of calcium = low blood
calcium. Body adjusts for this by obtaining calcium from resorption of bone (via
release of parathyroid hormone (PTH)). - decreased activation of vitamin D results in decreased absorption of calcium from gut
Why does Azotemia disturbance occur when renal function decreases below a critical level? What does this result in?
- Inability to excrete nitrogenous wastes - build-up of nitrogenous waste products in
blood - itching skin
- nausea, vomiting, decreased appetite, ulcers in mouth and GI tract.
- inflammation of tissue membranes (pericarditis, pleuritis)
- blood clotting problems - bleeding
- peripheral nerve and muscle dysfunction
- eventually drowsiness, coma, death
What is creatinine?
- A waste product of muscle metabolism.
- Kidneys filter most of the creatinine produced by the body
What does raised levels of creatinine in the blood mean?
Impaired kidney function
2 treatments of chronic renal faillure
- Dietary (avoid foods containing excess sodium, potassium, phosphate)
- Medical
i) Control of underlying conditions such as diabetes, hypertension
ii) Erythropoietin may help in certain cases of chronic anemia
iii) Dialysis
iv) Kidney transplant
Ranges of cystic diseases of the kidney
simple cysts which are incidental and extremely common to rare genetic and congenital diseases
Why are cystic diseases of the kidney clinically important? (3)
- Some are major causes of chronic renal failure.
- They can occasionally be confused with malignant tumors.
- Some forms are hereditary, and have implications for family members.
Where do cysts of the kidney develop from? What can this development be attributed to?
Renal tubular epithelium
- increased proliferation of tubular epithelium, altered differentiation, and excessive fluid
secretion
What do polycystic disorders result from
they result in the formation of numerous cysts,
often numbering in the hundreds
What kind of condition is polycystic disorder
Hereditary
Adult polycystic kidney disease has an _________ ________ inheritance pattern with no sex
or race predilection
Autosomal dominant
What 2 genes have been implicated in polycystic kidney disorder? Which one is the most common?
PKD1 and PKD2 genes coding for polycystin-1 and -2, respectively
PKD1 gene on chromosome16
What does the PKD1 gene on chromosome 16 code for?
a cell membrane protein (polycystin-1) which is
involved in cell-cell and cell-matrix interactions, and has been found in epithelial cells of the
kidney, liver, and pancrease
What does loss of the polycystin-1 protein coded by PKD1 result in?
results in altered growth regulation and differentiation of tubular epithelial cells, with cyst formation as a result
Adult polycystic disease is among the commonest causes of renal failure, often resulting in the
need for … later in life
dialysis or kidney transplant
What is among the commonest causes of renal failure
Adult polycystic disease
Adult polycystic disease effects which kidney?
BOTH
What does adult polycystic disease do to the kidneys? What can this damage lead to?
both are massively enlarged and much of the functional tissue is replaced by thin-walled cysts which contain clear to bloody fluid
-enlarging cysts compress and destroy the functional nephrons, until chronic renal failure results
Polycystic disease is not confined to the kidneys. Where else can it be found?
cycts in liver, pancreas, spleen and other organs
Patients with polycystic disease are also predisposed to what complication? What does this often result in (rather than complications of renal failure)?
They are also predisposed to aneurysms in the blood vessels of the brain, and 10-15% of patients will die of a brain hemorrhage as a result of aneurysm rupture
Adult Polycystic Kidney Disease vs. Infantile Polycystic Kidney Disease
Adult - kidney is enlarged and almost entirely replaced by cysts of varying size
Infantile - dilated cortical and medullary collecting ducts are arranged radially and external surface is smooth
What is the juvenile form of plycystic kidney disease
Different genes are affected than the adult type with an autosomal recessive inheritance pattern
When do patients with the juvenile form of plycystic kidney disease develop cysts? What is this form also predisposed to?
In childhood
-predisposed to a peculiar type of liver fibrosis
Diseases that effect the _____ are among the most important causes of chronic kidney failure in humans
Glomerulus
What are the 2 divisions of gomerular injury
- Primary glomerulopathies: diseases which affect the glomerulus primarily or exclusively e.g. IgA neprhropathy, post-streptococcal GN
- Secondary glomerulopathies: diseases which affect multiple organs, including the kidney. Examples would include diabetes, systemic lupus (SLE), and certain forms of vasculitis
What are most glomerular diseases a result from?
f an abnormal immune reaction resulting in
the deposition of antibodies or antigen-antibody immune complexes in the glomerular basement membrane
3 classic models of antibody-mediated glomerular injury
- Deposition of pre-formed circulating antibody-antigen immune complexes (e.g. postinfectious
glomerulonephritis; SLE) - Deposition of antigens in the glomerular basement membrane, to which antibodies
subsequently attach. - The body may also produce antibodies that directly attack the glomerular basement
membrane (Goodpasture’s disease, an example of an autoimmune condition).
What is the end result of any glomerular injury and how does this impair function?
Damage to the glomerular basement membrane which impairs the glomerulus’ ability to filter blood properly
What 2 things are tubular cells particularly sensitive to?
- lack of O2
2. exposure to toxins
What results in acute tubular necrosis (ATN) and what is this due to?
Major trauma, shock, burns, infections, nephrotoxic
drugs or poisons result in acute tubular necrosis (ATN), due to temporary lack of adequate oxygen or blood flow (ischemia, trauma, burns, shock) or direct chemical insult (toxins or poisons)
Microscopically, what happens to tubule cells during ATN
patchy loss and degeneration of the tubular epithelial cells
What is acute pyelonephritis
acute bacterial infection of the kidney
What do patients with acute pyelonephritis present with
fever, flank pain, flu-like symptoms
-often symptoms of associated bladder irritation–> pain during urination, increased frequency and feeling of urgency
How does bacteria usually reach the kidney
by spreading upstream from the urinary tract (ascending infection), bu also sometimes through the blood (hematogenous route)
Risk factors for acute pyelonephritis
are the same as for bladder infection and include obstruction, instrumentation, urine reflux, female gender, diabetes, and suppressed immune system
Is renal failure common with acute pyelonephritis? When can it occur?
It’s rare, only occurs in very serious infections, or if there are recurrent infections leading to chronic disease where longstanding obstruction, urine reflux, or repeated infections result in scarring of the kidney
What is chronic pyelonephritis? Micoscopically, what results?
a chronic disease where longstanding obstruction, urine reflux, or repeated infections result in scarring of the kidney with distortion of the pelvis and blunting of the renal papillae
-fibrosis, chronic inflammation and damage to the tubules
What can athersclerosis result in?
narrowing of the renal arteries, with resulting decreased blood flow, atrophy of the kidney, and chronic kidney failure
What immediate injury can athersclerosis cause and why?
RENAL CORTICAL INFARCTION
-when fragments of an atheromatous plaque in the heart, aorta or renal artery break off
-floating bits of debris or emboli (formed of clotted blood, cholesterol, lipid-filled macrophages and
other constituents) lodge in smaller arteries in the kidney
-sudden localized obstruction of blood flow results in death of the part of the kidney that was fed by the
affected blood vessel
What is a major cause of end stage renal failure? What can it result in?
Hypertension
-results in thickening of the walls of smaller arteries and arterioles (nephrosclerosis), scarring of the glomeruli, and decline in renal function
Explain how heredity can affect the occurrence of kidney stones
There is a hereditary predisposition to stone formation due to abnormal production and excretion of stone-forming substances
What medical conditions can kidney stones arise from?
hyperparathyroidism, chronic urinary tract infection; low fluid intake; diet -excess dietary calcium and/or overactive GI calcium absorption mechanisms
What are most kidney stones made of? What %?
75% calcium salts (as calcium oxalate and/or calcium
phosphate)
What makes up the remaining % of kidney stone types? (3)
-magnesium ammonium phosphate (struvite - seen in
chronic urinary infections, some bacteria can split urea into ammonium which combines with phosphate and magnesium)
-uric acid (Uric acid stones are common in patients with gout, who have high blood concentrations of uric acid),
-cystine
What is the main common factor in stone formation? What are other factors?
increased urinary concentration of the stone’s constituents, forming a supersaturated solution
that crystalizes in the urinary tract (e.g., hypercalcuria).
- Additional factors include…
high urine pH
decreased urine volume
deficiency in the production of stone inhibiting substances (e.g., magnesium, citrate)
Treatment options of kidney stones
- Drink lots of water and wait for spontaneous passage
- Shatter with sound waves (lithotripsy)
- Surgical removal
What is the most common tumor of the kidney termed?
Renal cell carcinoma
What populations are particularly vulnerable to renal cell carcinoma
These tumors occur more often in older people (60-70 yrs), and are twice as common in males (2-3:1 M:F). Renal cell carcinoma is a very common form of cancer; represents 2 to 3% of adult malignancies.
What is the major risk factor for renal cell carcinoma? What are other risks?
Smoking is a major risk factor. Other risk factors include obesity, and exposure to certain petroleum products, industrial chemicals, and heavy metals.
What are symptoms of renal cell carcinoma? When do they onset?
Often asymptomatic at first
- blood in the urine
- flank pain
- palpable mass
- weight loss
- loss of appetite
- fever
What is the gross appearance of renal cell carcinoma?
rounded mass with a yellow-orange cut surface with areas of hemorrhage and necrosis
What is urine reflux
from bladder back into ureter
What acts like a one-way flap-type valve to prevent retrograde flow of urine? What may occur if there is an anatomical defect of this valve / abnormal ureteric insertion point?
musculature and mucosa of the bladder
-urine reflux may occur
What are complications of urine reflux
- Urinary tract infection; pyelonephritis
- Hydroureter / hydronephrosis
- Chronic renal failure in advanced cases
Treatment of urine reflux
- Conservative: (observation, antibiotics, timed voiding, medications for bladder muscle
relaxation, etc) as many low grade cases will spontaneously resolve as child grows - Surgical (ureteral reimplantation)
Obstruction of the urinary tract may be _____ or ______
intrinsic or extrinsic
Intrinsic causes of UT obstruction
- Stones
- Congenital and acquired strictures
- Tumors, mainly of the ureters, bladder, and prostate
- Loss of normal neural pathways that control the bladder, e.g. from spinal cord injury
Extrinsic causes of UT obstruction
- Pregnancy - compression of the ureters by the
enlarging uterus. - Inflammation and scarring of surrounding organs,
e.g. endometriosis, salpingitis of the fallopian tube,
diverticulitis of the colon. - Tumors arising in adjacent pelvic or abdominal
organs
Obstruction of the UT may be…. ( choices)
acute or chronic, partial or complete, unilateral or bilateral
Symptoms of acute UT obstruction
pain
What type of obstruction is silent at first? What will eventually happen?
Unilateral or partial obstruction may remain silent for long periods of time. Eventually, there is dilatation of the ureter (hydroureter) and/or renal pelvis (hydronephrosis) proximal to the point of obstruction
What does chronic obstruction result in?
atrophy of the renal tubules, associated with chronic inflammation, scarring and permanent loss of renal function
What do obstruction, urine reflux (retrograde flow), and urine stasis (due to incomplete emptying of the
bladder) predispose to?
bacterial seeding and the development of urinary tract infections
What is the most common type of cancer in the UT
transitional cell carcinoma (TCC) since its all lines by transitional epithelium
Where is TCC most common? Where else can it be found?
most common in the bladder, but may also develop in the renal pelvis or ureters. Bladder cancer is very common, with 50,000 new cases diagnosed every year
in the US
What population is most susceptible to TCC
Patients are most often male, white and elderly.
What is TCC strongly linked to? How much does this group of peoples risk for TCC increase?
smoking: smokers have a 2-4X increased risk of bladder cancer compared with non-smokers
Other risk factors of TCC
- Occupational exposure to industrial chemicals (arylamines, nitrosamines,chlorinated hydrocarbons)
- Drugs - rarely! (e.g. phenacetin and cyclophosphamide)
What do the vast majority of bladder tumors classically present with?
painless hematuria (blood in the urine)
Two broad groups that TCC can be broken down into
Low grade and high grade
Aspects of low grade TCC
Grow slowly
Almost always have a papillary growth pattern (finger-like projections)
Tumor cells look relatively monotonous
Multifocal distribution
Recur frequently, but are seldom aggressive
Seldom invade, or invade only locally
Very small risk of metastasis
Aspects of high grade TCC
High rate of recurrence, and behave aggressively
More often flat or nodular; papillary component less pronounced
Cells proliferate as solid nests and cords with lack of orderly growth.
Tumor cells exhibit enlarged pleomorphic nuclei with prominent chromatin.
High risk for invasion. Invasion can be deep into bladder wall
High risk of metastasis to lymph nodes or distant sites
Survival rate for low grade lesions of the UT tract
95% 10-year survival rate; re-occurrence is common
Treatment of high-grade TCC
complete excision of the bladder (cystectomy) is performed
