Terms in this set (129)
The _________ contains most of the tubules and ducts of the nephrons and the ________ contains most of the filtration units. Which one has the higher concentration of sodium?
Medulla; Cortex: Medulla
This is the name of flat funnel shaped cavity that collects the urine to move into the ureters
True or False: Nephrons are located in the medulla.
True but nephrons are half in the medulla and half in the cortex. They lie perpendicular to the durface of the kidney.
Located in the cortex it is a sac that covers the glomerulus. Closed end at beginning of nephron (vascular pole). Open end is the urine pole
Ball of capillaries with fenestrated epithelium and incomplete basement membrane that is supported by modified epithelial cells called podocytes
"Little Feet" - epithelial cells in the glomerulus that allow filtration to occur easily
The podocytes are similar to what structure in the eye?
The choriocapillaris and the retinal pigment epithelial cells
Specialized smooth muscle cells mainly in the walls of the afferent arterioles. Interact with baroreceptors to sense pressure changes and produce, store and excrete renin!
Cells that hold the glomerulus together that have a phagocytic function and contractile capabilities to control blood flow
Constriction of the afferent arteriole...
Decreases blood flow
Constriction of the efferent arteriole...
Increases blood flow
Activation of the sympathetic system causes _________ of the afferent arteriole and release of ___________
constriction; release of renin from the juxtaglomerular cells
this slows down blood flow and decreases filtration pressure
The release of renin results in ....
angiotensin II development which leads to constriction of the efferent arteriole (thus, contraction of the afferent arteriole results in contraction of the efferent arteriole) - the reason being to achieve a constant rate of filtration
Filtration is active or passive?
filtration happens passively as blood passes through the glomerulus
The glomerulus has selective permeability influenced by the:
1) size of the substance
2) charge of the substance (the membrane has a negative charge, making positively charged substances more likely to go through)
3) configuration of the substance
What occurs during re absorption?
Substances such as ions, glucose and amino acids are pulled from the filtrate back into the blood stream
reabsorption of many substances is related to sodium reabsoprtion (by exchange, via shared transporters or via solvent drag)
Reabsorption has what 2 major modifiers:
1) Concentration of molecules - the more that are there, the more (up to point) that transporters can gather
2) Rate of flow of filtrate - faster flow decreases amount of time for transporter to gather ion
What amount of filtrate volume becomes urine?
only about 1%- the majority of water is reabsorbed!
What occurs during secretion?
a substance is added to the filtrate to be expelled from the body
this is usually unwanted substances such as ammonia and organic acids (what meds up as)
can be a function of a transporter cell or a passive process
In a healthy individual, what two things should not end up in the filtrate?
If the glomerulus is functioning properly, no RBCs or large proteins should enter the filtrate
Where does the majority of reabsorption occur? Name some substances that are reabsorbed
80% of reabsorption occurs in the PCT. H20, NaCl, bicarbonate, K, glucose, amino acids
What helps make the environment for the kidney?
The loop of henle
What can leave the descending loop of henle? How does it leave?
Only water can leave. This is generally a passive process that depends on the osmolarity in the medulla (which should be ~1200 mOsm)
Can water leave in the ascending loop of henle?
No. Ions such as NaCl and K+ can be actively transported to the blood but nothing else really moves
What happens to NaCl in the collecting duct?
NaCl can be exchanged for K+ (NaCl is reabsorbed). This can be increased by aldosterone
Vasopressin can ___________ reabsoprtion of water in the collecting duct
A diuretic that prevents absoprtion of bicarbonates at the PCT, not very effective
it is a carbonic anhydrase inhibitor
Prevent NaCl from being reabsorbed at the ascending loop of henle. This makes more NaCl in the collecting duct and increases the amount that is exchanged for K+. It can make a person K+ deficient if no supplement is taken.
Macula densa cells
chemoreceptors that respond primarily to a decreased conc. of sodium and chloride in the filtrate
decreased NaCl can happen when blood flow is too slow, macula dense cells say hey speed up
ie tachypnea (rapid breathing)
without life: nitrogen
bad, painful, difficult
ie dysuria (pain while urinating)
few, little, scant
ie endocrine (secrete within)
Renin always _________ (increases/ decreases) BP. It is released by the _____________
INCREASES! Renin is released by the juxtaglomerular cells
Liver releases angiotensinogen and kidney releases renin, together they form angiotensin I
angiotensin converting enzyme
it is released by the lungs and combines with angiotensin I to produce angiotensin II
Acts on the pituitary gland to influence the release of vasopressin and aldosterone
Acts on the PCT to increase the reabsorption of NaCl
Acts on the thirst centers in the brain
Vasopressin and Aldosterone response to angiotensin II
Released by the pituitary gland in response to angiotensin II. They both act on the kidneys to increase sodium and water reabsorption in an effort to increase the blood volume and thus blood pressure.
Where do anti-hypertensive drugs typically target?
They target the enzyme ACE that is released by the lungs to produce angiotensin II
What stimulates the secretion of vasopressin?
1) Angiotensin II
2) Decreased blood volume
3) Increased osmolarity of the blood (there are osmoreceptors located in the anterior hypothalamus)
The osmoreceptors in the anterior hypothalamus are most responsive to....
Sodium and mannitol but glucose also has some effect
Increased osmolarity of the blood causes the release of vasopressin (ADH) and an increased reabsorption of water to increase the blood volume and raise BP
Released by the kidney in response to hypoxia
Stimulates the bone marrow to produce RBCs
Why kidney diseases are often associated with blood diseases
Released by the kidneys to convert Vit D to its active metabolic form (Vit D3)
Important for absorbing Ca from the intestine
Dysfunction can lead to osteoporosis
What does the kidney have to do with glucose as an endocrine function?
The kidneys are involved in gluconeogensis
Vasoactive peptides released by the kidneys that can cause vasodilation or vasoconstriction
Vasoconstriction tends to cause an increase in BP and salt and water retention
released by the kidneys to cause more water to be excreted
helps macula densa provide feedback
counters endothelins to decrease BP!
released by the kidney to increase blood flow to the kidney by preventing vasoconstriction
this impairs water reabsorption by blocking vasopressin and preventing K+ excretion
overall leads to more water being excreted and a decrease in BP
What can counter renal prostaglandins? What is the effect?
NSAIDS and steroids can counter renal prostaglandins and decrease initial filtration leading to edema and an increase in BP
Kidney and acid-base balance
Kidneys control acid-base balance by regenerating bicarbonate, excreting H+ when blood becomes too acidic and excreted bicarbonate when blood becomes too alkaline
Glomerular Filtration Rate (estimated)
Normal is 115-125 ml/ min
Measured clinically by having pt ingest inulinin, a starch that is only removed by the glomerulus (like creatinine) and then collecting timed urine and blood samples
Creatinine Clearance Rate
Urine collected for 24 hours with blood draw at the end
Normal is 100 ml/min. Less than 60 is an indicator of kidney disease
Serum Creatinine Level
Less accurate version of CrCl but easier for the patient to do
Normal = 1.0 mg/100 ml. If it doubles, consider GFR and kidney function to have fallen to half its normal state
Needed to calculate estimated GFR along with age, size and gender
Test blood to look for conc of urea
Urea is the end product of protein metabolism that is filtered/ controlled by kidney function
A slow GFR will allow the tubular fluid to stay in the kidney and more urea will be reabsorbed
an increase in BUN (meaning a slow GFR) without symptoms
________ in urine may be one of the first signs of kidney involvement in DM
Which two ions tend to increase in conc. in the blood with kidney failure?
Potassium and phosphate. Can check pt's blood to look for elevated levels
An increase in K+ in the blood will cause _______ to leave the blood.
Ca2+ will leave the blood and aggregate in tissues like the conjunctiva. It is for this reason that it will be decreased in the blood with kidney failure
The pH of urine tends to ___________ (increase/ decrease) with kidney failure.
pH tends to decrease as well as the conc. of bicarbonate
Neutrophil gelatinase-associated lipocalin
a new test that is specifically for ACUTE damage
imaging that allows for visualization of the urethra, bladder and ureteral orifices that allows for biopsy
can be used to evaluate for structure, tumors and abnormalities
intravenous pyelogram - X-ray visualization of renal tissues as injected dye is cleared by the kidneys
What are the #1 and #2 causes of kidney failure?
When a patient has clinical signs and symptoms of azotemia it is called ________
What are often the first signs of chronic kidney disease?
first signs are often GI related - anorexia, nausea, vomiting and diarrhea
Acute Renal Failure can be caused by...
aka acute renal injury can be caused by meds, ischemia, autoimmune diseases, and/or infections
the number one cause of ischemia in N. America is from open heart surgery
How do NSAIDS cause kidney failure?
NSAIDs inhibit prostaglandin synthesis which can prevent vasodilation (which lowers BP)
Typically, discontinuing the drug will lead to resolution
Which medications can lead ARF?
NSAIDS, Penicillin, sulfonamides and Cipro all bind to the kidney and can set up an immune reaction (type I or type IV). They can trigger ARF even in low doses.
High doses of aminoglycosides (gentamicin) can lead to nephrotoxicity, as well as radiographic contrast agents
Acute Tubular Necrosis is __________ (intrinsic/ extrinsic) ARF
Intrinsic it is a response to acute ischemia or nephrotoxic insult
Acute tubular necrosis leads to ....
damage/ destruction to the tubular epithelial cells preventing them from transporting ions which affects the osmotic balance in the medulla
the cells can slough off and block the tubules causing an increase in intratubular pressure which can cause an abrupt decrease in GFR which causes a decrease in volume of urine and an increase in fluid vol in the body and waste products in the blood
What is malignant hypertension and how is it related to the eyes?
An uncommon and very bad form of hypertension
Sx: HA (possibly occipital), N, V, VISUAL Scotoma and spots
Diastolic BP >120 mmHg
It can cause optic nerve head edema, encephalopathy, CV abnormailities and renal failure
Describe the viscous cycle of malignant HTN
1) vascular damage to the kidneys
2) increased permeability of small vessels
4) ischemia to the kidney
5) release of more renin
6) more vasoconstriction
7) back to 1
Derangement of capillary walls of the glomerulus.
It leads to hypoalbuminemia - low blood protein! This causes the production of plasma proteins, including lipoproteins which cause hyperlipiduria and hyperlipidemia and an increased risk for thromboembolism
Massive proteinuria is a sign of ...... it can leads to what appearance in urine? What might also be in the urine?
nephrotic syndrome - it will cause the urine to bubbly
high amount of protein in the urine and very low amount of protein in the blood. in response to this the body will produce whatever proteins it can, including lipoproteins which is why there may also be high lipid conc. in the urine (and the blood)
What are the signs of nephrotic syndrome?
Generalized edema - eyelids are often first. Decreased albumin in the blood shifts the osmotic balance and causes more fluid to stay in the tissues
Hypertension - decreased blood to the kidneys will cause the release of renin
What disease can cause "Pitting" edema?
Nephrotic Syndrome. It is called "pitting" because if you apply pressure to the area, it will literally leave a pit in the skin
What causes nephrotic syndrome?
Diabetes, HTN, SLE, NSAIDs, memebranoproliferative glomerulonephritis or can be idiopathic
What are the treatments for nephrotic syndrome?
ACE inhibitors or ARBs to decrease BP and decrease the protein in the urine by improving charge and size selectivity of the glomerular basemement membrane
Fluid and sodium restriction
Statins if chronic
>90% respond to corticosteroids (most take for the rest of their life)
What is Alport Syndrome?
a rare genetic disorder that can be caused by many different mutations
it is nephritic syndrome that becomes nephrotic!
it affects the collagen in the basement membrane of the kidney, cochlea, lungs, lens capsule, Bruch's membrane, and Descemet's!
What are the systemic signs of alport syndrome?
First sign is usually hematuria. Proteinuria usually absent in childhood but develops later in life (and maybe to the point of nephrotic syndrome)
Later in life will also have HTN
What ocular findings may be associated with Alport?
1) Dot-and-fleck retinopathy
2) Anterior lenticonus (pathopneumonic)
3) Posterior polymorphous corneal dystrophy
4) temporal macular thinning
What are the treatments of Alport syndrome?
Avoid nephrotoxins (NSAIDs)
Kidney transplant if ESRD
What is acute glomerulonephritis?
it is also known as acute nephritic syndrome
it is an inflammatory condition that leads to an abrupt onset of hematuria and proteinuria with impaired renal function due to the retention of salt and therefore fluid
What are the signs of acute glomerulonephritis?
Hematuria, proteinuria, oliguria, mild edema (usually on eyelids and face first)
A prior infection such as strep throat or impetigo can lead to what kidney disease?
it can also be caused by sub-acute bacterial endocarditis, dental abscess or shunt infections, SLE, or it could be idiopathic
What is the treatment for acute glomerulonephritis? How long does it take to resolve?
Salt restriction, diuretics
Can take 1-2 years to recover but it rarely leads to chronic renal failure
What is membranoproliferative glomerulonephritis? What disease is it similar to in a appearance?
It is also known as Dense Deposit Disease
It is due to immune damage to capillaries and supporting mesangium
There are 3 subtypes and the cause is often unknown
It can cause HTN and signs of NEPHROTIC syndrome
Bilateral central clustered drusen in a teenage patient may be a sign of....
Type II membranoproliferative glomerulonephritis
Initially the patient's VA or VF will be unaffected, but long term consequences are poor night vision, SRNVM, macular detachment, CSR, and retinal atrophy
What is tubulointerstitial nephropathy?
a group of inflammatory kidney diseases that primarily involve the interstitum and tubules but SPARES the glomerulus and renal vessels
it can be acute or chronic
tubulointerstitial nephropathy uveitis
occurs in young patients (10-33) and mainly in females
it is BILATERAL (which uveitis is usually unilateral) and often recurrent
it may be accompanied by fever, weight loss and fatigue
Tx: oral corticosteroids
What is acute pyelonephritis? What are the signs and treatment?
An inflammation of the kidney and renal pelvis that is almost always due to bacteria getting to the kidney retrograde via bladder and ureters (why it is very common in women, esp during pregnancy)
Signs - fever, DYSURIA, back pain, and PYURIA (pus in urine)
What is chronic pyelonephritis? What are the signs?
Like acute, it is an inflammation of the kidney and renal pelvis. Often the only first signs are general malaise but may also have pyuria.
Primary underlying disorder is frequent UTI from obstruction, diabetic nephropathy, etc
Many with it end up on dialysis
Is a person with acute or chronic pyelonephritis more likely to end up on dialysis?
What is the relationship between diabetic nephropathy and the kidneys?
DM leads to metabolic changes that can cause microalbuminuria and proteinuria as well as nephrotic syndrome and azotemia and eventually ESRD
What is Fabry Disease?
An error of glycosphingolipid metabolism due to enzyme (alpha-galactosidase A) defect
It is genetic (x-linked recessive) but carriers sometimes show manifestations
it is difficult to diagnose because of the variability of the signs of the symptoms but most are related to its cause of a build up of lipids in the tissues
Children with Fabry may experience? What tests can be done to confirm diagnosis?
Burning sensations in the hands, raised rash mostly on buttocks, groin, and things, and a decreased ability to sweat
Can do an enzyme assay measure the amount of alpha-gal activity and/ or genetic testing. To treat have to do enzyme replacement with a recombinant agent every 2 weeks intravenously for life
What are the ocular signs of Fabry disease?
The most common and first ocular sign seen is a corneal whorl or verticillata.
There is also changes in vasculature than can lead to conj vessel tortuosity and saccular dilation
In 40-60% of cases they also have spoke-like cataracts
What are the systemic problems of Fabry disease?
RENAL FAILURE - Proteinuria, azotemia or uremia due to glycolipid deposition and damage to renal vessels. This occurs in 50% of all patients by 35 and the rest by 55.
Will also have cardiovascular disease, GI dysfunction, etc
What is Nephrolithiasis? Is it more common in males or females?
Kidney stones! The formation of calculus in the collecting system that develops in the pelvis and then usually gets stuck in the ureter
they are very common overall (1/20 will experience it in their lifetime) but are 5-10x more likely in males
Renal Cell Carcinoma prevalence/ distribution
80-90% of all malignant tumors of kidney (2% of all cancers in adults)
2:1 male dominated. Greater frequency in cigarette smokers
Renal Cell carcinoma may be associated with what disease?
Von Hippel-Lindau disease - a vascular abnormaility in which anastomoses throughout the body (including the retina) are abnormal.
Since the kidneys are highly vascular they are also affected. renal cell carcinoma usually develops in the proximal tubules
What is the most common manifestation of renal cell carcinoma? What are the other signs/ symptoms?
The most common is PAINLESS hematuria but may have dull flank pain and a palpable flank mass. May also have long-standing fever, elevated ESR, weight loss and fatigue
What is the treatment for renal cell carcinoma?
Surgical removal of kidney or new treatment is percutaneous cryoablation
Can also use anti-VEGF and anti-PDGFR. They are exploring immune modulators like aldesleukin
5 yr survival rate
What is the prevalence/ distribution of Wilms' tumor? What is its ocular association?
it is the second most common kidney malingnacy and
the third most common organ cancer in children less than 10 (high incidence in children with aniridia)
tumor can grow to incredible size and cause abdominal distension
Decrease the reabsorption of Na to increase urine output
Initially they decrease the blood volume but this may return to normal with time, esp. if kidney function is normal
Used to treat HTN
diuretic that decreases Na reabsorption and calcium secretion in the distal convoluted tubule
long term effect is increased vasodilation
Act on the collecting duct to prohibit reabsoprtion of Na in exchange for K+
May also inhibit aldosterone
Which anti-hypertensive meds may be used in diabetics and others with kidney disease to decrease the amount of protein in the urine?
ACE inhibitors, ARBs (angiotensin II antagonists), renin inhibitors or calcium channel blockers
What is the criteria for the initiation of dialysis?
If looking at GFR alone - 15 ml/min for diabetics and <10ml/min for nondiabetics
However, studies show that this may actually be too soon! Now suggested to wait until there are symptoms or uremia - such as edema that is not responsive to diuretics, acidosis, persisent hyperkalemia, neuropathy, etc
You suspect acute nephritic syndrome in your patient. Which question would be LEAST helpful for you to ask?
Any joint pain?
Any recent dental procedures?
Any family history of kidney disease?
Any recent illness or infection?
Any changes in urination?
Any family history is the least helpful because nephritic syndrome is not genetic
remember that it can be cause by autoimmune conditions such as SLE which would cause joint pain
What diet does a person on hemodialysis have to maintain?
High protein (opposite of chronic renal failure), high potassium, decreased sodium, decreased fluids
What are the advantages/ disadvantages of CAPD?
CAPD = continuous ambulatory peritoneal dialysis. It is where they insert a catheter into the peritoneal cavity and you walk around with a bag of dialysate and a bag of waste products so that there is constant filtration (peritoneum acts as a semipermeable membrane)
Adv - less dietary restrictions then hemodialysis, more constisten filtration, get to maintain normal-ish lifestyle, residual kidney function retained longer, more cost efficient
Dis - bags must be changed in sterile env, risk of peritonitis
85% of those who receive a kidney transplant will be taking..... What is another possible drug?
1) Tacrolimus - (calcineurin inhibitor) decreases IL-2 production by T cells to prevent self-replication
2) Azathioprine - (anti-metabolite, DMARD) decreases lymphocyte proliferation and activation
50% also taking corticosteroids (pred) but this number is decreasing due to the risks
What are the complications with transplantation?
1) immunosuppresive disorders
2) Secondary HTN due to pred and native kidney renin production
3) UTI, hepatitis, pneumonia
4) malignancy (100x > risk for skin cancer)
5) graft rejection
What is the ocular relevance in Kaposi's sarcoma?
it can first show up in the eye as a subconjunctival hemorrhage
if you see this on a transplant patient be concerned
Which antibiotic can be used with no renal adjustment?
Azithromycin because it is excreted in the bile primarily
Which 2 diseases lead to eyelid edema? What are the differences?
1) Nephrotic Syndrome - eyelids are often first but unique in that it causes a "pitting edema"
2) Acute glomerulonephritis - also characterized by proteinuria but it usually more of a sudden onset and is commonly associated with a recent prior infection. It is nephritic - due to an inflammatory condition.
During tubular reabsorption in the proximal tubule of the nephron, most solutes are moved across the apical membrane by __________ , and across the basal membrane by __________ .
During tubular reabsorption in the proximal tubule of the nephron, most solutes are moved across the apical membrane by cotransport, and across the basal membrane by facilitated diffusion.
The permeability of the distal tubule and the collecting duct is controlled by______________
Renal tubules are __________ permeable to urea than they are to water, therefore urea concentration in the tubules __________ .
Which of these substances is actively transported into the filtrate in the proximal and distal tubule?
A) H+ ions
B) Na+ ions
D) amino acids
E) Cl- ions