the second week on the kidney: beginning with tubular disorders. the normal function of the renal tubules is reabsorption of various electrolytes, thus many tubular disorders result in excess amounts of these materials in the urine. fanconi's syndrome is a congenital or acquired syndrome that is often fatal by the 20's that leads to dysfunction of the proximal tubule, resulting in cystinosis, glucosuria, phosphaturia, aminoaciduria, bicarbonate wasting. cystinuria and aminoaciduria are failed reabsorption of cysteine or amino acids in general, leading to excess excretion in the urine. in both, cystine crystals might form and create symptoms similar to that of a patient with renal colic. wilson's disease is a rare congenital disease that involves copper deposition in the tubules, along with the liver, brain, and RBC's. the pathognomonic sign for wilson's disease is the "kayser fleischer" rings seen in the eye.
renal glucosuria is a tubular dysfunction that results in spilling of glucose into the urine despite normal or low blood glucose levels. it is often asymptomatic and might be found by glucose in the urine after a 24 hour fast. renal acidosis is another condition that involves acidosis which might be due to impaired secretion of H+ in the distal tubule or impaired reabsorption of bicarbonate in the proximal tubule. the latter might be associated with potassium wasting and muscle dysfunction as well. potassium absorption can also be affected by tubular dysfunction, as seen in bartter's and liddle's syndrome. nephrogenic diabetes insipidus is a congenital and generally fatal disease that might show up in infants in which the kidney's ADH receptors are dysfunctional, resulting in polydipsia, polyuria and hypotonic urine.
diabetic nephropathy is a complication that occurs in about 1/3 of cases of diabetes mellitus which involves glycosylation of the nephron and the dysfunction that results. it might occur 15-20 years after a diagnosis of DM and might be heavily influenced (or prevented) by diet and lifestyle factors early on. the first signs are not overt and may include increased GFR and mild proteinuria. patients with stage II DN will see a drop in GFR, more noticeable proteinuria (resulting in edema symptoms as well), and increasing hypertension. stage III is the last stage, the last few years of a ~20 year process which involves greatly reduced GFR, massive proteinuria, hypertension, and retinopathy. patients with severe DN are at increased risk for infections as well due to the higher glucose levels in the urine.
polycystic kidney disease is a hereditary disorder that results in multiple bilateral cysts that increase size and decrease function of the kidneys. it can manifest as proteinuria, mild hematuria, low back pain, infection, and colic due to formation of stones. late stage, it might also be accompanied by hepatic involvement such as portal HTN and esophageal varices. it will show proteinuria and hematuria on lab diagnosis, as well as pyuria which might appear even without infection. 50% of patients with PKD will end up with renal failure in 10 years.
interstitial tubular disorder is another possible tubular dysfunction that occurs due to drug toxicity or hypersensitivity- most commonly from seizure medication. these drugs can affect both the tubules and the interstitial space, causing a variety of symptoms including that of tubular dysfunction, renal failure, UTI, as well as a host of dermatological manifestations depending on the causative agent. labs might resemble an infection without the presence of bacteria: eosinophilia, proteinuria, hematuria. a patient with ITD would present clinically with enlarged kidneys.
cystitis is a UTI of the bladder, commonly due to vaginal uptake in women and chronic bacterial prostatitis in men. it manifests mostly through urinary symptoms: frequency, urgency, dysuria, occasional hematuria, and possibly suprapubic or lower back pain. there are generally no remarkable PE findings other than general achiness. a UA might show turbid urine and possibly hematuria.
if acute infection reaches the kidneys, acute pyelonephritis results. this condition is more common in girls / pregnant women or patients who have urethral instrumentation. it is most commonly due to e.coli, klebsiella, enterobacter and proteus, which may be present in a urine culture in excess of 100,000 / ml. symptoms include fever/chills/nausea/vomiting, as well as kidney tenderness and enlargement, and possible urinary symptoms as well. lab tests might show neutrophilia, bacteruria, and presence of WBC casts is a pathognomonic sign.
untreated or poorly managed acute pyelonephritis might lead to chronic pyelonephritis, which in turn may lead to chronic renal failure if fibrosis is widespread enough. these patients have a vague and inconsistent clinical presentation, sometimes having fever, abdominal/flank pain, and obstructive symptoms. a PE for a patient with CP should include checking for HTN and anemia symptoms, as well as edema, CVA tenderness, and palpation of the kidney and bladder. definitive diagnosis is made by IVU.
interstitial cystitis is a disorder of the bladder lining, related to dysfunction of the GAG layer. rather than an infectious origin, IC is commonly triggered by such foods as cranberry juice, potassium rich foods, coffee, alcohol, tomatoes, etc. it presents as a more severe cystitis, with urgency, frequency, and severe abdominal pain which can be severe enough to limit sexual activity. diagnosis is made by excluding other bladder conditions and can be made definitively by bladder wall biopsy, which would show hunnel's patches: tiny ulcerations.
a urinary calculi is a stone in the ureter, commonly made of calcium oxalate, struvite, uric acid, or cystine. they appear more frequently in men and are often idiopathic, although several risk factors have been identified- such as low water intake, excess vitamin C intake, and a sedentary lifestyle. people with UC will present with episodes of severe, colicky flank pain that may radiate down to the thigh, as well as hematuria and urinary symptoms. a UA might show hematuria, pyuria, and crystals-- a 6 sided crystal points to a stone made of cystine.
some notes on cancers of the kidney and bladder: most kidney tumors are adenocarcinomas, which are commonly caused by drugs and environmental toxins and might present asymptomatically due to the high functional reserve of the kidneys. wilm's tumor mostly affects children and may present as an asymptomatic mass. neuroblastoma is a systemic, often fatal condition which affects the kidney as well and can be identified by blackness around the eyes. bladder tumors are most often caused by cigarette smoking, and can cause hematuria, secondary infection, flank pain with obstructive symptoms. the conventional treatment strategy is sloughing off of cancer cells via instillation of BCG within the bladder.
questions
various tubular disorders...
1. what is fanconi's syndrome?
2. what is the prognosis for patients with fanconi's syndrome?
3. what is cystinuria?
4. patients with cystinuria can present similarly to which condition?
5. what is aminoaciduria?
6. cystine renal stones in a patient with aminoaciduria might indicate...
7. how is aminoaciduria diagnosed?
8. what is wilson's disease?
9. wilson's disease might present similarly to...
10. what is the pathognomonic sign for wilson's disease?
11. what is the prognosis for patients with wilson's disease?
12. if diagnosed early, what might be of benefit to patients with wilson's disease?
more tubular disorders...
13. what is renal glucosuria?
14. how is renal glucosuria diagnosed?
15. what is renal acidosis?
16. renal acidosis from proximal tubule dysfunction often accompanies which disease?
17. distal tubule dysfunction is often accompanied by...
18. what is bartter's syndrome?
19. what is liddle's syndrome?
20. what is nephrogenic diabetes insipidus?
21. what are the signs and symptoms of nephrogenic diabetes insipidus?
diabetic nephropathy...
22. what is diabetic nephropathy?
23. describe the hallmarks of the first stage of diabetic nephropathy. how long after DM diagnosis is the onset?
24. what are the hallmarks of the second stage of diabetic nephropathy?
25. what are the hallmarks of the third stage of diabetic nephropathy?
26. patients with diabetic nephropathy are more prone to...
27. what is the treatment strategy for patients in stage I DN?
28. what is the survival rate for stage II or III DN patients who need dialysis?
polycystic kidney disease...
29. what is polycystic kidney disease?
30. what are the signs and symptoms of PKD?
31. what are some symptoms that might appear late in the course of PKD?
32. what are the lab results for PKD?
33. what is the prognosis for PKD?
interstitial tubular disease...
34. what is ITD?
35. what are medications that commonly trigger ITD?
36. what are the signs and symptoms of ITD?
37. what are some typical lab results for a patient with ITD?
38. what is a PE finding one might find on a patient with ITD?
renal / urinary tract infections...
39. what are some general symptoms of a lower UTI?
40. what are some general symptoms of an upper UTI?
41. blood borne infections are more likely seen in which demographic?
42. what are some physiological mechanisms that fight against infections in the urinary tract?
43. what are some factors that predispose an individual to getting a UTI?
cystitis...
44. what is a common etiology of cystitis for females?
45. what is the most common etiology of cystitis for males?
46. what are the typical cystitis PE findings?
47. what are the signs and symptoms of cystitis?
48. what are some lab findings for cystitis?
acute pyelonephritis...
49. which demographic is AP most common in?
50. which microorganisms are most commonly implicated in AP?
51. what are the signs and symptoms of AP?
52. what are the lab markers one might see with an AP patient?
53. a urine culture might show...
chronic pyelonephritis...
54. CP accounts for what percentage of renal failure cases?
55. what is CP caused by?
56. how does CP lead to renal failure?
57. what is the symptom picture for CP?
58. CP symptoms might appear similarly to what other condition?
59. what should be checked for on a PE of a patient with CP?
60. definititve diagnosis of CP is made by...
61. what are some strategies for improving kidney health?
interstitial cystitis...
62. what gender is more affected by IC?
63. what is the pathophysiology of IC?
64. what are some common foods that irritate IC?
65. how does IC present clinically?
66. 60% of patients with IC experience...
67. how long does IC generally take to diagnose?
68. what are the diagnostic criteria for IC?
69. what is the pathognomonic sign for IC?
70. what is unique about the UA for patients with IC?
urinary calculi...
71. which gender is more prone to UC?
72. 75% of urinary calculi are due to what etiology?
73. 20% of urinary calculi are due to...
74. what are the most common types of stones found in UC?
75. what are the signs and symptoms of UC?
76. what might be found on a urinalysis of UC?
77. 6 sided crystals in a UA of UC is indicative of...
78. what are some risk factors for UC?
cancer...
79. what percentage of kidney tumors is represented by adenocarcinomas?
80. what are some etiological agents in adenocarcinoma of the kidneys?
81. what are the signs / symptoms of adenocarcinoma?
82. wilm's tumor is most common in which demographic?
83. wilm's tumor most commonly presents as...
84. what is a characteristic sign for neuroblastoma?
85. what is a common etiology for bladder cancer?
86. what are the signs and symptoms of bladder cancer?
answers
1. congenital or acquired dysfunction of proximal tubule that results in cystinosis, glucosuria, phosphaturia, aminoaciduria, and bicarbonate wasting.
2. most die in 20's.
3. impaired reabsorption of cysteine in the tubules which causes increased urinary excretion and formation of cystine calculi.
4. renal colic.
5. impaired absorption of all amino acids.
6. chronic renal failure.
7. excess amino acids and cystine crystals on UA.
8. a rare congenital disorder which involves copper deposition in various places in the body such as the renal tubules, liver, brain, RBC's.
9. hepatitis.
10. kayser fleischer rings.
11. generally poor due to late diagnosis.
12. treatment with zinc.
13. inherited condition that involves low blood glucose combined with excess excretion of glucose.
14. normal or low serum glucose but glucose in urine after overnight fast.
15. chronic acidosis which results either from impaired resorption of bicarbonate in proximal tubule or impaired secretion of H+ in distal tubule.
16. fanconi's syndrome, wilson's disease, multiple myeloma, vitamin D deficiency, heavy metal toxicity.
17. potassium wasting and the resulting muscle dysfunction.
18. hypokalemia due to dysfunction in thick ascending loop of henle.
19. rare disorder that resembles primary aldosteronism with hypertension and hyperkalemic alkalosis.
20. dysfunction of ADH receptors on the kidney.
21. polydipsia, polyuria, hypotonic urine.
22. a complication that occurs in about a third of cases of diabetes mellitus resulting from glycosylation of the nephron.
23. may appear 15-20 years after DM diagnosis; undetectable increase in GFR, mild proteinuria.
24. decreased GFR
proteinuria
edema due to low protein
hypertension.
25. azotemia (increases seen in BUN and creatinine)
GFR less than 1/3
massive proteinuria
hypertension
retinopathy
26. infections due to higher glucose levels in urine, neurogenic bladder, hypertension.
27. watch diet: low sugars, high vegetables
monitor blood pressure
watch for retinal fundus changes
28. 2-3 years.
29. an autosomal dominant or recessive disease that results in multiple bilateral cysts that increase the size and reduce the function of the kidneys.
30. asymptomatic, or
lumbar pain
hematuria
infection
colic due to stones [back blood bugs stones] [bloody stones on the back of bugs]
31. hepatic symptoms: portal HTN, esophageal varices.
32. proteinuria, occasional hematuria, pyruria (even without infection)
33. 50% chance for kidney failure in 10 years.
34. acute renal failure due to drug reaction / hypersensitivity that affects tubules and interstitial tissue.
35. seizure medications.
36. variable:
UTI sxs
tubular dysfunction sxs
oliguria
urticaria, photosensitivity, erythema nodosum, epidermal necrolysis
37. eosinophilia, proteinuria, hematuria, but no bacteria.
38. enlarged kidneys.
39. more urinary symptoms: dysuria, frequency, urgency, hematuria, etc. suprapubic pain.
40. kidney tenderness, fever/chills, N/V, sometimes diarrhea.
41. IV drug users.
42. immune response via WBC's and antibodies, urine acidity, and voiding.
43. congenital malformations (hypospadias)
poor or ineffective hygiene
frequent intercourse, anal sex
high urine pH
catheterization
low water intake
high carb diet / diabetes
44. uptake of bacteria from vagina.
45. chronic bacterial prostatitis.
46. patient in general distress and malaise, but not as severe as pyelonephritis.
47. dysuria, urgency, frequency, nocturia
suprapubic and lower back pain
48. turbid urine and occasional hematuria.
49. girls / pregnant women, or patients with catheterization.
50. e.coli, klebsiella, proteus, enterobacter.
51. fever/chills, N/V
flank pain, kidney tenderness and enlargement
urinary frequency / urgency in 1/3.
52. elevated neutrophils, bacteria, WBC casts in the urine.
53. more than 100,000 organisms / ml.
54. 2-3%.
55. recurrent acute pyelonephritis.
56. CP leads to fibrosis which decreases renal function, ultimately leading to chronic renal failure.
57. vague, inconsistent. may have
fever
flank / abdominal pain
obstructive symptoms
58. chronic interstitial nephritis.
59. signs of HTN, anemia, edema, CVA tenderness, palpation of kidneys and bladder.
60. IVU.
61. drink more water (up to half your weight??)
regulate protein intake
reduce unnecessary medications
62. females 10:1.
63. disruption of interior lining of the bladder, related to dysregulation of GAG layer. may also be abnormal accumulation of mast cells.
64. cranberry
coffee / tea
alcohol / tobacco
tomatoes
potassium
65. as a more severe cystitis:
frequency, urgency (enough to keep housebound) and severe abdominal pain
66. pain with intercourse.
67. 4.5 years on avg.
68. exclusion of other bladder conditions
irritative voiding
specific cystography changes or
aggravation from potassium
69. hunner's patches: tiny ulcerations seen in bladder wall biopsy.
70. consistently free of bacteria, unlike many other bladder conditions; not infective.
71. 3-4 times more common in males.
72. idiopathic.
73. uric acid abnormalities.
74. calcium oxalate, struvite, uric acid, cystine.
75. hematuria
episodes of severe, spastic, colicky pain that may radiate from flank to thigh
urinary symptoms: urgency, frequency, dysuria.
76. may have hematuria, pyuria, crystals.
77. cystine crystals.
78. low fluid intake
sedentary lifestyle
excess vitamin C
low vitamin B6, mg
79. 86%.
80. drugs
heavy metals
radiation
viruses
lifestyle factors: smoking, coffee, etc.
81. often asx because of high functional reserve of kidneys, but may present with colic, hematuria.
82. children.
83. asymptomatic mass.
84. black under the eyes.
85. smoking.
86. hematuria
infection
obstructive symptoms, flank pain
Showing posts with label kidneys. Show all posts
Showing posts with label kidneys. Show all posts
Sunday, April 25, 2010
Monday, April 19, 2010
CPD III: kidneys part I
the kidney unit in CPD III. we started with some introductory notes about diagnosis and the general symptom picture. labs that are helpful in the diagnosis of kidney conditions include urinalysis (can detect infection, RBC's, casts, etc), CBC, and chem screen (BUN and creatinine are useful measures of glomerular function). imaging studies might include xray, US, IVU, depending on the condition suspected. some typical symptoms associated with kidney conditions: UTI's commonly present with a triad of symptoms, urinary frequency, urgency, dysuria. chills/fever in association with these symptoms might indicate involvement of the upper urinary tract. urethral discharge in males is most likely due to GC/chlamydia infection. nocturia might be indicative of BPH, or simply reflect excess nighttime fluid consumption- consider nocturia seriously if it is a sudden change for the patient. enuresis, bedwetting, can be primary or secondary- patients with secondary enuresis might only have episodes followed by breaks of 6 months or more and are more likely due to psychological as opposed to physiological factors. incontinence comes in three flavors- overflow from incomplete emptying due to obstruction, stress from increased pressure, and urge from decreased CNS inhibition.
renal colic, or kidney stones, often cause severe unilateral pain in a crescendo-decrescendo pattern that radiates from the kidney / flank area to the lower abdomen and bladder, and sometimes as far down as the knee. patients might also present with nausea/vomiting, hematuria, and urinary frequency, as well as chills/fever if an infection is involved. diagnosis is made by UA and imaging, in particular US and IVU.
polyuria can be a physiologic response to an increased osmolar load, in which case the major concern is loss of electrolytes. it can also point to certain underlying pathologies such as diabetes insipidus, which leads to an underproduction of ADH by the pituitary. nephrogenic diabetes insipidus can also result in polyuria- in this condition, the kidney's ADH receptors are non functioning.
oligouria and anuria are conditions of decreased urine and can be from pre-renal, renal, or post renal causes. pre-renal causes can include dehydration, as well as any condition that decreases blood flow to the kidney such as CHF or hemorrhage. renal causes are grouped under the acronym VINDICATE: vascular lesions, inflammatory lesions, neoplasm, degenerative conditions, intoxication, congenital disorders, autoimmune, trauma, endocrine causes. post renal: MINNT-- malformations, inflammatory, neoplasm, neurological, trauma.
some notes about the various colors of urine and what they might indicate: normal color is yellow, although bright / concentrated yellow might indicate dehydration or B vitamins. overly clear might indicate glomerular dysfunction as in chronic glomerulonephritis, or simply polydipsia. cloudy white might be indicative of infection as the cloudiness might be bacteria or pus. red might be RBC's but can also be from certain foods such as beets.
as the kidneys are primarily responsible for maintaining fluid volume in the body, systemic edema symptoms often point to kidney filtration issues. pitting edema refers to a type in which fluid can be displaced, forming transient "pits", whereas in non-pitting, fluid can not be displaced- this is often due to local trauma such as a bee sting. in general edema formation can occur via four mechanisms- increased capillary pressure, increased capillary permeability, decreased plasma proteins, and lymph obstruction. edema symptoms may also point to other organ systems, in particular heart dysfunction (recall that RCHF leads to systemic edema), thyroid (hypothyroid myxedema), hepatic (look for jaundice, ascites, palmar erythema), and might even be due to a worm found in pork, trichinosis if seen periorbitally.
acute renal failure describes a situation marked by rapidly increasing azotemia plus oliguria / anuria. as with azotemia, the cause may be pre-renal (CHF), renal (glomerulonephritis), or post renal (bladder outlet obstruction, BPH). clinically, it manifests as lethargy, pulmonary edema, CHF, hypertension, and oliguria. diagnosis is made via chem screen, CBC, and UA-- most helpful is the rapid and steady increase of creatinine (as well as BUN). if oliguria / anuria persists for more than 3 days, this is an indicator of poor prognosis; conventional emergency treatment might require dialysis and complete kidney rest.
whereas acute renal failure might produce sudden increases in BUN / creatinine, chronic renal failure might show mild elevations for month long periods. there are many risk factors that contribute to CRF, such as glomerulonephritis, cardiovascular disease, SLE, pyelonephritis, etc. clinical presentation can be divided by the stage of disease: CRF initially presents with nonspecific / vague symptoms, or fatigue / mental haze. the intermediate stage presents with bad taste in mouth, muscle spasm/convusion/neuropathy, pruritis, nausea / vomiting. the late stage presents with cardiovascular issues such as hypertension, CHF, pericarditis, as well as skin issues such as uremic frost and yellow/brown complexion. in addition to the BUN / creatinine levels, one might expect to see normochromic / normocytic anemia (deficient erythropoetin production), waxy casts on a UA, and imbalanced electrolytes. these patients are generally put on dialysis long term (200,000 in the US) with dietary / fluid intake monitoring- in particular, avoiding high protein intake.
nephrotic syndrome results from a dysfunctional or damaged glomerular basement membrane, leading to loss of proteins and hyperlipidemia. it can be primary from diseases such as immune complex nephritides, or secondary to systemic illness such as diabetes mellitus. patients might present with frothy urine, marked edema periorbitally and peripherally, muscle wasting due to lack of protein, and respiratory symptoms. diagnosis is made by UA, chem screen, CBC- UA might show proteins, cellular elements, casts. chem screen might show hyperlipidemia, hyperalbuminemia, and CBC might show microcytic anemia.
acute glomerulonephritis is another form of glomerular dysfunction, this time from immune complex deposition from previous infection, such as an untreated strep throat infection. it commonly affects children and young adults and is relatively rare in adults over 50. although it has mild proteinuria as nephrotic syndrome does, the hallmark of AG is hematuria and presence of RBC casts in the UA. the decreased glomerular function also leads to increased sodium retention, which ultimately increases blood volume and may lead to hypertension or CHF. children have a good chance of recovery from AG but will always have an increased risk for HTN-- thus an adult who has unexplained HTN might have had acute glomerulonephritis earlier in life. chronic glomerulonephritis might result from longstanding acute glomerulonephritis and might develop insidiously- patients might asx, but with occasional proteinuria and hematuria, with RBC casts on a UA. steadily increasing BUN might also be observed over months or years.
goodpasture's is a near fatal glomerular disease that has a predilection for young males. the hallmark signs are lung and renal hemorrhage that results in hemoptysis and hematuria. labs have the combined characteristics of nephrotic syndrome and glomerulonephritis: hematuria / RBC's, but also with protein / casts in UA, along with increased BUN / creatinine. patients might also present with headache, malaise, and anorexia. the prognosis for goodpasture's is poor, and patients with this condition rarely live past their 20's.
idiopathic primary renal hematuric/proteinuric syndrome is diagnosed when there is mild gross or microscopic hematuria and proteinuria without any clear explanation. the etiology may be related to IgA towards the glomeruli, as well as buerger's disease and febrile URI's. this condition has a preference for males and children-- most recover but like acute glomerulonephritis have an increased lifetime risk for hypertension and renal insufficiency.
henoch-schoenlein purpura is similar to IPRHPS but with marked skin, GI, and joint involvement- the characteristic purpura lesions are symmetrically distributed on the extensor surfaces. GI symptoms might include abdominal pain, vomiting, and joint pain may occur at the ankles, hands, feet. HSP generally follows a viral infection, such as an acute viral URI. lab findings might show hematuria / proteinuria, occult blood, and increased ESR. HSP is self limiting, generally within 6 weeks, although 10-20% of patients might develop chronic renal failure.
questions
diagnosis...
1. what are some helpful lab tests to consider when ruling in or out kidney related pathologies?
2. what are two components of a chem screen that can give an indication of kidney function?
3. what are the imaging techniques used to diagnose kidney conditions?
4. what is the "triad of symptoms" seen in UTI's?
5. what might chills/fever indicate in a patient with the triad of symptoms for a UTI?
6. leukocyte casts in a UA might indicate...
7. what is the most common cause of urethral discharge in males?
8. what might nocturia be indicative of?
9. what is the difference between primary and secondary enuresis?
10. what are the different types of incontinence?
renal colic...
11. describe the pain sensation in renal colic.
12. describe the typical radiation patterns seen in renal colic pain.
13. what are some concomitant symptoms seen in renal colic?
14. what is a typical PE of a patient with RC?
15. what would labs show for RC?
16. what are the imaging studies used to diagnose RC?
polyuria...
17. what are some pathological conditions associated with polyuria?
18. why does diabetes insipidus cause polyuria?
19. what is nephrogenic diabetes insipidus?
oligo / anuria...
20. what are some prerenal causes of oligouria or anuria?
21. what are some renal causes of oligouria / anuria?
22. what are some post renal causes of oligouria / anuria?
what might be indicated by urine that is...
23. colorless.
24. cloudy white.
25. yellow.
26. orange.
27. red.
28. blue/green.
29. brown/black.
edema...
30. what is the difference between pitting and non-pitting edema?
31. what is a common cause of non-pitting edema?
32. what are four pathophysiological mechanisms for edema formation?
33. what are some hepatic symptoms or conditions that might be associated with edema?
34. what is a thyroid related etiology for edema?
35. what is the relationship between edema and pork?
acute renal failure...
36. what is acute renal failure?
37. what are the major etiologies of acute renal failure?
38. what are some "pre-renal" causes of acute renal failure?
39. what are some "renal" causes of acute renal failure?
40. what are some "post-renal" causes of acute renal failure?
41. what are some of the signs and symptoms of acute renal failure?
42. what are some labs that aid in the diagnosis of acute renal failure?
43. if anemia is present in acute renal failure, what type of anemia would it be?
44. what is a marker for prognosis of acute renal failure?
45. what is the conventional treatment strategy for acute renal failure?
chronic renal failure...
46. what are some risk factors for CRF?
47. how many patients in the US are currently on dialysis long term?
48. what are the early signs / symptoms for CRF?
49. what are the intermediate stage signs/symptoms for CRF?
50. what are the late stage signs/symptoms for CRF?
51. what are the lab tests used to diagnose CRF?
52. what are some electrolyte imbalances one might expect to see in CRF?
53. what is the connection between CRF and chronic anemia?
54. what are some treatment strategies for CRF?
nephrotic syndrome...
55. what is nephrotic syndrome?
56. which gender is more affected by nephrotic syndrome?
57. what are the etiologies of nephrotic syndrome?
58. what are the signs and symptoms of nephrotic syndrome?
59. what might one expect to find on a UA of a pt with NS?
60. what might one expect to find on a chem screen of a pt with NS?
61. what is the connection between nephrotic syndrome and hyperlipidemia?
62. what might be a finding on a CBC of a pt with NS?
63. what are some PE findings for NS?
acute glomerulonephritis...
64. what is AG? what are the hallmarks of AG?
65. what age group is most commonly affected by AG?
66. what is the etiology of AG?
67. how long after an episode of untreated strep throat might AG appear?
68. what are the signs/symptoms of AG?
69. what is the lab finding that is diagnostic for AG?
70. what might be seen in fundoscopy of a pt with AG?
71. what is the prognosis for children with AG?
chronic glomerulonephritis...
72. what is chronic glomerulonephritis?
73. what is a typical presentation for chronic glomerulonephritis?
goodpasture's syndrome...
74. which demographic is most commonly affected by goodpasture's syndrome?
75. what are the hallmark signs and symptoms of GS?
76. what are the concomitant symptoms of GS?
77. what are common lab findings for GS?
78. what is the prognosis of goodpasture's syndrome?
idiopathic primary renal hematuric/proteinuric syndrome...
79. what is IPRHPS?
80. what are some possible etiologies of IPRHPS?
81. what demographic is most closely associated with IPRHPS?
82. what might be a predisposing factor for IPRHPS?
83. what might lab findings show for IPRHPS?
84. what is the prognosis for IPRHPS?
henoch-schoenlein purpura...
85. what is HSP?
86. what is the etiology of HSP?
87. what are the signs and symptoms of HSP?
88. what are some lab findings one might expect to find with HSP?
89. what is the prognosis of HSP?
answers
1. UA, culture, CBC, chem screen.
2. BUN and creatinine: both excreted by the kidneys and therefore can be a rough indicator for glomerular function.
3. Xray, US, IVU.
4. urinary frequency, urgency, pain.
5. upper UTI.
6. renal parenchyma infection.
7. GC chlamydia.
8. early disease, excess fluid consumption in evening, BPH, interstitial cystitis.
9. in secondary, there might be a period of dryness (over 6 months)-- more likely due to psychological factors.
10. overflow (obstruction of urinary tract leads to incomplete emptying), stress (increased intraabdominal pressure), urge (decreased CNS inhibition).
11. severe, unilateral, crescendo-decrescendo pain.
12. from flank/kidney around to lower abdomen, follows course of urinary tract and sometimes radiates down further, as far as knee.
13. chills/fever
N/V
hematuria
frequency
14. unremarkable or flank tenderness.
15. hematuria with or without pyuria / bacteruria.
16. xray, US, IVU (for kidney and ureter).
17. diabetes insipidus, nephrogenic diabetes insipidus, psychogenic polydipsia.
18. in DI, the pituitary underproduces ADH, a hormone that allows for water reabsorption in the kidney- thereby leading to greater urine output.
19. a condition where the kidney's receptors for ADH are not functioning.
20. dehydration, hemorrhage, CHF.
21. VINDICATE:
vascular lesions
inflammatory lesions
neoplasm
degenerative
intoxication
congenital disorders
autoimmune (most common)
trauma
endocrine
22. MINNT:
malformations
inflammation
neoplasms
neurological disorders
trauma
23. polydipsia, chronic glomerulonephritis, diabetes inspidis/mellitus.
24. phosphates, epithelial cells, bacteria/pus.
25. B vitamins.
26. urobilinogen, bile, pyridium, carrots.
27. beets, or RBC's.
28. certain drugs (thymol, phenol, indigo blue), pseudomonas.
29. bilirubin, hemoglobin.
30. in pitting, fluid can be displaced and transient "pits" are formed. in non-pitting, edema is so severe that fluid can not be displaced.
31. trauma causes coagulation of proteins such as fibrinogen.
32. increased capillary pressure (blood clots, CHF)
increased capillary permeability (CHF)
decreased plasma proteins (burns, nephrosis, low protein intake)
lymph obstruction (lymph node removal, parasites)
33. jaundice
ascites
spider nevi
red nose
palmar erythema
34. there is a marked increase in water retention in hypothyroid myxedema.
35. trichinosis is a worm found in pork that is associated with periorbital edema.
36. rapidly increasing azotemia plus oliguria.
37. 60-70% extrinsic factors: trauma, drugs, surgery, obstruction, etc.
20-30% due to intrinsic factors: acute glomerulonephritis, SLE, goodpasture's, etc.
38. renal failure that results from inadequate renal perfusion due to factors upstream from the kidney: CHF, hemorrhage, etc.
39. decreased renal blood flow, reduced glomerular filtration, or renal obstruction.
40. bladder outlet obstruction, BPH, tumors.
41. lethargy
pulmonary edema
CHF
hypertension
oliguria
42. chem screen: steadily increasing creatinine is diagnostic. also see BUN increase.
CBC to check for anemia and infection
UA to check for RBC's, WBC's, casts.
43. normocytic normochromic.
44. oliguria / anuria for more than 3 days indicates very poor prognosis; may be fatal.
45. dialysis to allow kidney to recover, or severe limitation of fluid and electrolyte intake.
46. glomerulonephritis
cardiovascular diseases such as arteriosclerosis, HTN
SLE, diabetes
congenital abnormalities (polycystic kidney)
pyelonephritis
47. about 200,000.
48. non-specific
fatigue
nocturia
mental haze
49. muscle twitching, aches, convulsions
neuropathy
bad taste in mouth
N/V
pruritis
50. uremic frost
GI ulcers / bleeding
tissue wasting
yellow / brown skin
hypertension / CHF / pericarditis
51. chem screen would show mild / moderate elevations of BUN/creatinine over months
CBC would show normocytic / normochromic anemia,
UA might show waxy casts
52. decreased calcium, increased phosphorous, potassium, CO2.
53. kidney failure leads to improper erythropoetin production.
54. dietary and fluid intake monitoring - decrease protein and increase carb intake.
55. damage to the glomerular basement membrane that causes hyponaturia, proteinuria, hypoalbuminemia, lipiduria, hyperlipidemia.
56. males.
57. primary nephrotic disease such as immune complex nephritides or underyling systemic disease such as diabetes mellitus.
58. frothy urine
edema
muscle wasting
abdominal pain
SOB/DOE
[basement pee edema muscle stomach breath] [basement flooded with pee- use your stomach muscles and blow it out]
59. cellular elements, protein, casts.
60. hyperalbuminemia and hyperlipidemia.
61. the liver increases lipid production (cholesterol) concurrently with protein production in an attempt to normalize protein levels from the protein loss incurred in nephrotic syndrome.
62. microcytic anemia.
63. periorbital and peripheral edema
muscle wasting
parallel white lines on nails
orthostatic hypotension
64. glomerular dysfunction which causes decreased GFR and increased Na retention, leading to hematuria and hypertension.
65. young children older than 3 or young adults. rare in >50yos.
66. previous infection which causes immune complex deposition in glomeruli.
67. 1-6 weeks.
68. hematuria / oliguria
flank pain
mild edema
hypertension
69. RBC casts on a UA.
70. retinal hemorrhages.
71. 90% chance of recovery but increased risk for HTN remains throughout lifetime.
72. diffuse sclerosis of glomeruli and insidious loss of kidney function.
73. asx, with no abnormal lab results except for occasional proteinuria and hematuria. steadily increasing BUN over years.
74. young males 9:1.
75. renal and lung hemorrhage-- hemoptysis and hematuria.
76. headache, malaise, anorexia.
77. increased BUN/creatinine, RBC, protein on UA, microcytic anemia on CBC.
78. poor, patients rarely live past 20's.
79. presence of protein and RBC's in urine with no explanation.
80. glomerular IgA deposition, buerger's disease.
81. 6:1 males, children/young adult most common.
82. febrile URI.
83. hematuria, proteinuria, increased IgA.
84. many children recover but have an increased lifetime risk for hypertension and renal insufficiency.
85. similar to IPRHPS but with skin, joint, and GI involvement.
86. often follows a viral infection, acute URI.
87. symmetrically distributed purpura on extensor surfaces
arthritis
GI distress- vomiting, pain, occult blood
hematuria, proteinuria
88. increased ESR
hematuria / proteinuria
occult blood
89. self limiting in 1-6 weeks. 10-20% have chronic renal failure.
renal colic, or kidney stones, often cause severe unilateral pain in a crescendo-decrescendo pattern that radiates from the kidney / flank area to the lower abdomen and bladder, and sometimes as far down as the knee. patients might also present with nausea/vomiting, hematuria, and urinary frequency, as well as chills/fever if an infection is involved. diagnosis is made by UA and imaging, in particular US and IVU.
polyuria can be a physiologic response to an increased osmolar load, in which case the major concern is loss of electrolytes. it can also point to certain underlying pathologies such as diabetes insipidus, which leads to an underproduction of ADH by the pituitary. nephrogenic diabetes insipidus can also result in polyuria- in this condition, the kidney's ADH receptors are non functioning.
oligouria and anuria are conditions of decreased urine and can be from pre-renal, renal, or post renal causes. pre-renal causes can include dehydration, as well as any condition that decreases blood flow to the kidney such as CHF or hemorrhage. renal causes are grouped under the acronym VINDICATE: vascular lesions, inflammatory lesions, neoplasm, degenerative conditions, intoxication, congenital disorders, autoimmune, trauma, endocrine causes. post renal: MINNT-- malformations, inflammatory, neoplasm, neurological, trauma.
some notes about the various colors of urine and what they might indicate: normal color is yellow, although bright / concentrated yellow might indicate dehydration or B vitamins. overly clear might indicate glomerular dysfunction as in chronic glomerulonephritis, or simply polydipsia. cloudy white might be indicative of infection as the cloudiness might be bacteria or pus. red might be RBC's but can also be from certain foods such as beets.
as the kidneys are primarily responsible for maintaining fluid volume in the body, systemic edema symptoms often point to kidney filtration issues. pitting edema refers to a type in which fluid can be displaced, forming transient "pits", whereas in non-pitting, fluid can not be displaced- this is often due to local trauma such as a bee sting. in general edema formation can occur via four mechanisms- increased capillary pressure, increased capillary permeability, decreased plasma proteins, and lymph obstruction. edema symptoms may also point to other organ systems, in particular heart dysfunction (recall that RCHF leads to systemic edema), thyroid (hypothyroid myxedema), hepatic (look for jaundice, ascites, palmar erythema), and might even be due to a worm found in pork, trichinosis if seen periorbitally.
acute renal failure describes a situation marked by rapidly increasing azotemia plus oliguria / anuria. as with azotemia, the cause may be pre-renal (CHF), renal (glomerulonephritis), or post renal (bladder outlet obstruction, BPH). clinically, it manifests as lethargy, pulmonary edema, CHF, hypertension, and oliguria. diagnosis is made via chem screen, CBC, and UA-- most helpful is the rapid and steady increase of creatinine (as well as BUN). if oliguria / anuria persists for more than 3 days, this is an indicator of poor prognosis; conventional emergency treatment might require dialysis and complete kidney rest.
whereas acute renal failure might produce sudden increases in BUN / creatinine, chronic renal failure might show mild elevations for month long periods. there are many risk factors that contribute to CRF, such as glomerulonephritis, cardiovascular disease, SLE, pyelonephritis, etc. clinical presentation can be divided by the stage of disease: CRF initially presents with nonspecific / vague symptoms, or fatigue / mental haze. the intermediate stage presents with bad taste in mouth, muscle spasm/convusion/neuropathy, pruritis, nausea / vomiting. the late stage presents with cardiovascular issues such as hypertension, CHF, pericarditis, as well as skin issues such as uremic frost and yellow/brown complexion. in addition to the BUN / creatinine levels, one might expect to see normochromic / normocytic anemia (deficient erythropoetin production), waxy casts on a UA, and imbalanced electrolytes. these patients are generally put on dialysis long term (200,000 in the US) with dietary / fluid intake monitoring- in particular, avoiding high protein intake.
nephrotic syndrome results from a dysfunctional or damaged glomerular basement membrane, leading to loss of proteins and hyperlipidemia. it can be primary from diseases such as immune complex nephritides, or secondary to systemic illness such as diabetes mellitus. patients might present with frothy urine, marked edema periorbitally and peripherally, muscle wasting due to lack of protein, and respiratory symptoms. diagnosis is made by UA, chem screen, CBC- UA might show proteins, cellular elements, casts. chem screen might show hyperlipidemia, hyperalbuminemia, and CBC might show microcytic anemia.
acute glomerulonephritis is another form of glomerular dysfunction, this time from immune complex deposition from previous infection, such as an untreated strep throat infection. it commonly affects children and young adults and is relatively rare in adults over 50. although it has mild proteinuria as nephrotic syndrome does, the hallmark of AG is hematuria and presence of RBC casts in the UA. the decreased glomerular function also leads to increased sodium retention, which ultimately increases blood volume and may lead to hypertension or CHF. children have a good chance of recovery from AG but will always have an increased risk for HTN-- thus an adult who has unexplained HTN might have had acute glomerulonephritis earlier in life. chronic glomerulonephritis might result from longstanding acute glomerulonephritis and might develop insidiously- patients might asx, but with occasional proteinuria and hematuria, with RBC casts on a UA. steadily increasing BUN might also be observed over months or years.
goodpasture's is a near fatal glomerular disease that has a predilection for young males. the hallmark signs are lung and renal hemorrhage that results in hemoptysis and hematuria. labs have the combined characteristics of nephrotic syndrome and glomerulonephritis: hematuria / RBC's, but also with protein / casts in UA, along with increased BUN / creatinine. patients might also present with headache, malaise, and anorexia. the prognosis for goodpasture's is poor, and patients with this condition rarely live past their 20's.
idiopathic primary renal hematuric/proteinuric syndrome is diagnosed when there is mild gross or microscopic hematuria and proteinuria without any clear explanation. the etiology may be related to IgA towards the glomeruli, as well as buerger's disease and febrile URI's. this condition has a preference for males and children-- most recover but like acute glomerulonephritis have an increased lifetime risk for hypertension and renal insufficiency.
henoch-schoenlein purpura is similar to IPRHPS but with marked skin, GI, and joint involvement- the characteristic purpura lesions are symmetrically distributed on the extensor surfaces. GI symptoms might include abdominal pain, vomiting, and joint pain may occur at the ankles, hands, feet. HSP generally follows a viral infection, such as an acute viral URI. lab findings might show hematuria / proteinuria, occult blood, and increased ESR. HSP is self limiting, generally within 6 weeks, although 10-20% of patients might develop chronic renal failure.
questions
diagnosis...
1. what are some helpful lab tests to consider when ruling in or out kidney related pathologies?
2. what are two components of a chem screen that can give an indication of kidney function?
3. what are the imaging techniques used to diagnose kidney conditions?
4. what is the "triad of symptoms" seen in UTI's?
5. what might chills/fever indicate in a patient with the triad of symptoms for a UTI?
6. leukocyte casts in a UA might indicate...
7. what is the most common cause of urethral discharge in males?
8. what might nocturia be indicative of?
9. what is the difference between primary and secondary enuresis?
10. what are the different types of incontinence?
renal colic...
11. describe the pain sensation in renal colic.
12. describe the typical radiation patterns seen in renal colic pain.
13. what are some concomitant symptoms seen in renal colic?
14. what is a typical PE of a patient with RC?
15. what would labs show for RC?
16. what are the imaging studies used to diagnose RC?
polyuria...
17. what are some pathological conditions associated with polyuria?
18. why does diabetes insipidus cause polyuria?
19. what is nephrogenic diabetes insipidus?
oligo / anuria...
20. what are some prerenal causes of oligouria or anuria?
21. what are some renal causes of oligouria / anuria?
22. what are some post renal causes of oligouria / anuria?
what might be indicated by urine that is...
23. colorless.
24. cloudy white.
25. yellow.
26. orange.
27. red.
28. blue/green.
29. brown/black.
edema...
30. what is the difference between pitting and non-pitting edema?
31. what is a common cause of non-pitting edema?
32. what are four pathophysiological mechanisms for edema formation?
33. what are some hepatic symptoms or conditions that might be associated with edema?
34. what is a thyroid related etiology for edema?
35. what is the relationship between edema and pork?
acute renal failure...
36. what is acute renal failure?
37. what are the major etiologies of acute renal failure?
38. what are some "pre-renal" causes of acute renal failure?
39. what are some "renal" causes of acute renal failure?
40. what are some "post-renal" causes of acute renal failure?
41. what are some of the signs and symptoms of acute renal failure?
42. what are some labs that aid in the diagnosis of acute renal failure?
43. if anemia is present in acute renal failure, what type of anemia would it be?
44. what is a marker for prognosis of acute renal failure?
45. what is the conventional treatment strategy for acute renal failure?
chronic renal failure...
46. what are some risk factors for CRF?
47. how many patients in the US are currently on dialysis long term?
48. what are the early signs / symptoms for CRF?
49. what are the intermediate stage signs/symptoms for CRF?
50. what are the late stage signs/symptoms for CRF?
51. what are the lab tests used to diagnose CRF?
52. what are some electrolyte imbalances one might expect to see in CRF?
53. what is the connection between CRF and chronic anemia?
54. what are some treatment strategies for CRF?
nephrotic syndrome...
55. what is nephrotic syndrome?
56. which gender is more affected by nephrotic syndrome?
57. what are the etiologies of nephrotic syndrome?
58. what are the signs and symptoms of nephrotic syndrome?
59. what might one expect to find on a UA of a pt with NS?
60. what might one expect to find on a chem screen of a pt with NS?
61. what is the connection between nephrotic syndrome and hyperlipidemia?
62. what might be a finding on a CBC of a pt with NS?
63. what are some PE findings for NS?
acute glomerulonephritis...
64. what is AG? what are the hallmarks of AG?
65. what age group is most commonly affected by AG?
66. what is the etiology of AG?
67. how long after an episode of untreated strep throat might AG appear?
68. what are the signs/symptoms of AG?
69. what is the lab finding that is diagnostic for AG?
70. what might be seen in fundoscopy of a pt with AG?
71. what is the prognosis for children with AG?
chronic glomerulonephritis...
72. what is chronic glomerulonephritis?
73. what is a typical presentation for chronic glomerulonephritis?
goodpasture's syndrome...
74. which demographic is most commonly affected by goodpasture's syndrome?
75. what are the hallmark signs and symptoms of GS?
76. what are the concomitant symptoms of GS?
77. what are common lab findings for GS?
78. what is the prognosis of goodpasture's syndrome?
idiopathic primary renal hematuric/proteinuric syndrome...
79. what is IPRHPS?
80. what are some possible etiologies of IPRHPS?
81. what demographic is most closely associated with IPRHPS?
82. what might be a predisposing factor for IPRHPS?
83. what might lab findings show for IPRHPS?
84. what is the prognosis for IPRHPS?
henoch-schoenlein purpura...
85. what is HSP?
86. what is the etiology of HSP?
87. what are the signs and symptoms of HSP?
88. what are some lab findings one might expect to find with HSP?
89. what is the prognosis of HSP?
answers
1. UA, culture, CBC, chem screen.
2. BUN and creatinine: both excreted by the kidneys and therefore can be a rough indicator for glomerular function.
3. Xray, US, IVU.
4. urinary frequency, urgency, pain.
5. upper UTI.
6. renal parenchyma infection.
7. GC chlamydia.
8. early disease, excess fluid consumption in evening, BPH, interstitial cystitis.
9. in secondary, there might be a period of dryness (over 6 months)-- more likely due to psychological factors.
10. overflow (obstruction of urinary tract leads to incomplete emptying), stress (increased intraabdominal pressure), urge (decreased CNS inhibition).
11. severe, unilateral, crescendo-decrescendo pain.
12. from flank/kidney around to lower abdomen, follows course of urinary tract and sometimes radiates down further, as far as knee.
13. chills/fever
N/V
hematuria
frequency
14. unremarkable or flank tenderness.
15. hematuria with or without pyuria / bacteruria.
16. xray, US, IVU (for kidney and ureter).
17. diabetes insipidus, nephrogenic diabetes insipidus, psychogenic polydipsia.
18. in DI, the pituitary underproduces ADH, a hormone that allows for water reabsorption in the kidney- thereby leading to greater urine output.
19. a condition where the kidney's receptors for ADH are not functioning.
20. dehydration, hemorrhage, CHF.
21. VINDICATE:
vascular lesions
inflammatory lesions
neoplasm
degenerative
intoxication
congenital disorders
autoimmune (most common)
trauma
endocrine
22. MINNT:
malformations
inflammation
neoplasms
neurological disorders
trauma
23. polydipsia, chronic glomerulonephritis, diabetes inspidis/mellitus.
24. phosphates, epithelial cells, bacteria/pus.
25. B vitamins.
26. urobilinogen, bile, pyridium, carrots.
27. beets, or RBC's.
28. certain drugs (thymol, phenol, indigo blue), pseudomonas.
29. bilirubin, hemoglobin.
30. in pitting, fluid can be displaced and transient "pits" are formed. in non-pitting, edema is so severe that fluid can not be displaced.
31. trauma causes coagulation of proteins such as fibrinogen.
32. increased capillary pressure (blood clots, CHF)
increased capillary permeability (CHF)
decreased plasma proteins (burns, nephrosis, low protein intake)
lymph obstruction (lymph node removal, parasites)
33. jaundice
ascites
spider nevi
red nose
palmar erythema
34. there is a marked increase in water retention in hypothyroid myxedema.
35. trichinosis is a worm found in pork that is associated with periorbital edema.
36. rapidly increasing azotemia plus oliguria.
37. 60-70% extrinsic factors: trauma, drugs, surgery, obstruction, etc.
20-30% due to intrinsic factors: acute glomerulonephritis, SLE, goodpasture's, etc.
38. renal failure that results from inadequate renal perfusion due to factors upstream from the kidney: CHF, hemorrhage, etc.
39. decreased renal blood flow, reduced glomerular filtration, or renal obstruction.
40. bladder outlet obstruction, BPH, tumors.
41. lethargy
pulmonary edema
CHF
hypertension
oliguria
42. chem screen: steadily increasing creatinine is diagnostic. also see BUN increase.
CBC to check for anemia and infection
UA to check for RBC's, WBC's, casts.
43. normocytic normochromic.
44. oliguria / anuria for more than 3 days indicates very poor prognosis; may be fatal.
45. dialysis to allow kidney to recover, or severe limitation of fluid and electrolyte intake.
46. glomerulonephritis
cardiovascular diseases such as arteriosclerosis, HTN
SLE, diabetes
congenital abnormalities (polycystic kidney)
pyelonephritis
47. about 200,000.
48. non-specific
fatigue
nocturia
mental haze
49. muscle twitching, aches, convulsions
neuropathy
bad taste in mouth
N/V
pruritis
50. uremic frost
GI ulcers / bleeding
tissue wasting
yellow / brown skin
hypertension / CHF / pericarditis
51. chem screen would show mild / moderate elevations of BUN/creatinine over months
CBC would show normocytic / normochromic anemia,
UA might show waxy casts
52. decreased calcium, increased phosphorous, potassium, CO2.
53. kidney failure leads to improper erythropoetin production.
54. dietary and fluid intake monitoring - decrease protein and increase carb intake.
55. damage to the glomerular basement membrane that causes hyponaturia, proteinuria, hypoalbuminemia, lipiduria, hyperlipidemia.
56. males.
57. primary nephrotic disease such as immune complex nephritides or underyling systemic disease such as diabetes mellitus.
58. frothy urine
edema
muscle wasting
abdominal pain
SOB/DOE
[basement pee edema muscle stomach breath] [basement flooded with pee- use your stomach muscles and blow it out]
59. cellular elements, protein, casts.
60. hyperalbuminemia and hyperlipidemia.
61. the liver increases lipid production (cholesterol) concurrently with protein production in an attempt to normalize protein levels from the protein loss incurred in nephrotic syndrome.
62. microcytic anemia.
63. periorbital and peripheral edema
muscle wasting
parallel white lines on nails
orthostatic hypotension
64. glomerular dysfunction which causes decreased GFR and increased Na retention, leading to hematuria and hypertension.
65. young children older than 3 or young adults. rare in >50yos.
66. previous infection which causes immune complex deposition in glomeruli.
67. 1-6 weeks.
68. hematuria / oliguria
flank pain
mild edema
hypertension
69. RBC casts on a UA.
70. retinal hemorrhages.
71. 90% chance of recovery but increased risk for HTN remains throughout lifetime.
72. diffuse sclerosis of glomeruli and insidious loss of kidney function.
73. asx, with no abnormal lab results except for occasional proteinuria and hematuria. steadily increasing BUN over years.
74. young males 9:1.
75. renal and lung hemorrhage-- hemoptysis and hematuria.
76. headache, malaise, anorexia.
77. increased BUN/creatinine, RBC, protein on UA, microcytic anemia on CBC.
78. poor, patients rarely live past 20's.
79. presence of protein and RBC's in urine with no explanation.
80. glomerular IgA deposition, buerger's disease.
81. 6:1 males, children/young adult most common.
82. febrile URI.
83. hematuria, proteinuria, increased IgA.
84. many children recover but have an increased lifetime risk for hypertension and renal insufficiency.
85. similar to IPRHPS but with skin, joint, and GI involvement.
86. often follows a viral infection, acute URI.
87. symmetrically distributed purpura on extensor surfaces
arthritis
GI distress- vomiting, pain, occult blood
hematuria, proteinuria
88. increased ESR
hematuria / proteinuria
occult blood
89. self limiting in 1-6 weeks. 10-20% have chronic renal failure.
Wednesday, February 4, 2009
organ systems: embryology of the urinary systems
[picture courtesy of erika yosefah william shortbread zelfand]
this lecture is the last in the series of the kidney and looks at renal embryology. kidney development can be roughly divided into three phases: pronephros, mesonephros, and metanephros. pronephros is both the early evolutionary form of the renal filtering system and also the first stage in human kidney development. mesonephros has nephrons with glomeruli and s-shaped tubules, which filter blood from the aorta and drain it into the gut tube via the mesonephric duct. the formation of the last stage, metanephros, begins with signalling factors from the metanephrogenic mesenchyme that stimulate the growth of the "uretic bud" from the lower part of the mesonephric duct. the uretic bud branches out and anastomoses to form the renal tubules and framework for the kidney. one additional note regarding early development: the urorectal septum divides the gut tube into the anorectal canal and the urogenital sinus, which form the urinary and GI tracts.
some pathologies of kidney development: if kidney fails to "ascend" (a misnomer because the kidney stays in place while the body grows downwards) to its position deep to the 12th rib, this is called pelvic kidney. horseshoe kidney is the fusion of the kidneys below the inferior mesenteric artery, and a failure to ascend. duplications of a kidney / supernumerary kidney can occur if the uretic bud divides prior to the development of the metanephric mesoderm. agenesis is the lack of development of uretic bud, leading to inadequate contact between mesoderm and uretic bud, leading to lack of a kidney.
questions
1. urogenital and reproductive systems develop from..
2. early nephrons develop in...
3. what are the three stage is kidney development?
4. what are the characteristics of the mesonephros stage?
5. urine formation begins...
6. describe the excretion of metabolic waste in the embryo.
7. uretic bud branches out from...
8. what are the renal tubules formed by?
9. metanephrogenic mesenchyme initiates growth of uretic bud via...
10. what are the collecting ducts formed by?
11. what is the "ascent of the kidney"?
12. what is the urorectal septum's role in renal development?
13. what is pelvic kidney?
14. what is horseshoe kidney?
15. what is duplications of the kidney?
16. what is agenesis of the kidney?
answers
1. urogenital ridges of intermediate mesoderm.
2. lateral part of urogenital ridge.
3. pronephros, mesonephros, metanephros
4. nephrons consisting of glomeruli and S-shaped tubules, which filter blood from the aorta, and a duct that drains into the gut tube.
5. ~9 weeks
6. metabolic wastes are dumped into the gut via the mesonephric duct, absorbed into blood and transported across placental wall for removal.
7. mesonephric duct
8. repeated dichotomous branching of the developing metanephron.
9. signalling factors
10. uretic bud
11. the apparent ascent due to the growth of the embryo caudal to the kidneys.
12. the urorectal septum divdes the gut tube into the GI tube and the urinary system.
13. no ascent of kidney
14. kidneys fuse below inferior mesenteric artery and do not ascend
15. double kidneys develop because ureteric bud divides prior to development of metanephric mesoderm
16. lack of development of uretic bud leading to inadequate contact between bud and mesoderm.
Tuesday, February 3, 2009
organ systems: acid base balance and urinary system
this lecture is an introduction to body pH and the mechanisms that regulate it: the kidneys, the lungs, and chemical buffers. it also talks about the development of kidney stones and the physiology of the bladder.
body pH is largely determined by the balance between the acidic carbon dioxide and the basic bicarbonate. recall from respiratory physiology that carbon dioxide combines with water in cells via carbonic anhydrase to form carbonic acid, which then dissociates into bicarbonate and H+. the body can develop alkalosis or acidosis due to an imbalance of these molecules; acidosis can occur either by hypoventilation (retaining too much CO2) or through metabolic pathways- loss of bicarbonate through diarrhea, renal failure, buildup of lactic acid from exercise, excess ketone body production in the case of diabetes mellitus. alkalosis can occur by hyperventilation (loss of too much CO2 from lungs) or by ingestion of antacids, excess secretion of H+ in the kidneys due to hypertension, or vomiting of acidic HCl.
in order to regulate the pH, the body can increase or decrease the ventilation rate to regulate blood CO2 levels. another main source of pH regulation is in the kidneys via the balance between reabsorption and excretion of bicarbonate and H+. bicarbonate in the blood is filtered in the kidneys and combines with H+ secreted by the epithelial cells of the proximal tubule. this forms carbonic acid, which can be converted back into CO2 and H2O via carbonic anhydrase. the CO2 then diffuses back into the epithelial cells, where it reforms bicarbonate and H+ through the reverse reaction. in this way 99% of bicarbonate filtered through the kidney is reabsorbed.
if the acidity in the blood is too high, then H+ secreted into the lumen will be higher than the bicarbonate in the filtrate, and excess H+ will be bound to ammonia and phosphate buffers and excreted, raising the pH. conversely, if the blood is basic, then there will be more bicarbonate than H+, and the excess will be unable to be reabsorbed as CO2 and thus be excreted, lowering the pH. angiotensin II and aldosterone can both cause excess H+ secretion, resulting in low pH- angiotensin II stimulates the PCT Na+/H+ cotransporters in the tubular epithelia, while aldosterone stimulates the Na+/H+ antiporter, as well as stimulating intercalated cell secretion of H+. this means that the high angiotensinII and aldosterone levels associated with hypertension also result in a lower pH.
a brief look at kidney stones: when there is excess insoluble material in the filtrate or excess water reabsorption, sometimes stones can develop in the kidney and block urine passage. the most common is the calcium oxalate stone, which develops from a hyper-reabsorption of calcium and oxalate from the intestines, which then combine in the kidneys. a second type of kidney stone is struvite, which forms from a bacterial enzyme, urease, which degrades urea into NH3, which raises pH and forms MgNH4PO4 stones.
the urine that forms in the kidney then goes out via the ureters into the bladder. the bladder is surrounded by the detrusor muscle, and has openings that lead out into the urethra, which leads out into the outside world. the urethral sphincter has two layers, the inner sphincter, which is controlled by parasympathetic smooth muscle, and the outer layer, which is controlled by voluntary striated muscle (pudendal nerve, S2,3,4). when the bladder is filling, the detrusor muscle relaxes and the inner sphincter contracts. during the micturition (urination) reflex, the detrusor muscle contracts and the inner sphincter relaxes.
questions
1. what is blood pH regulated by?
2. what is the main chemical buffer in the blood?
3. how do the lungs regulate pH?
4. how do the kidneys regulate pH?
5. what are the pH limits of the body and what occurs beyond the limits?
6. what are the sources of acidity in the body?
7. acidity depends on the ratio between...
8. the reaction that produces bicarbonate from CO2 is catalyzed by...
9. what is the pKa of bicarbonate and what happens at the physiologic pH of 7.4?
10. why is urine continuously acidified?
11. what are the two sources for production of CO2 in the body?
12. describe the ultimate fate of CO2.
13. describe the reabsorption of bicarbonate in the proximal convoluted tubules of the kidney.
14. describe the reabsorption of bicarbonate in the proximal convoluted tubules when there is an acid load.
15. describe acid secretion in the distal convoluted tubules.
16. what is the phosphate buffer? what does it do?
17. what is the major buffer system for excess H+ ions?
18. ammonium buffer produced from...
19. describe the path of the ammonium buffer through the nephron.
20. what is "bicarbonate addition"?
21. how do low potassium levels contribute to an acid urine?
22. what effect does angiotensin II have on H+ secretion?
23. what are the three ways in which aldosterone increases H+ secretion?
24. what is the body's response to respiratory acidosis?
25. what is the body's response to respiratory alkalosis?
26. what are four potential causes of metabolic acidosis?
27. what is the body's response to metabolic acidosis?
28. what are three potential causes of metabolic alkalosis?
29. what is the body's response to metabolic alkalosis?
30. what is the cause of kidney stones?
31. what is the most common type of kidney stone and what is it caused by?
32. what are struvite stones and how are they formed?
33. what is the muscle that contracts in the bladder?
34. what is the trigone?
35. in males, external and internal urethral sphincters are separated by...
36. how long is the urethra in males vs. females?
37. describe the difference between the internal vs. external urethral sphincters in females.
38. bladder filling is mediated by the...
39. baroreceptor sensory neurons in the bladder stimulates...
40. pressure waves are ...
41. what is the nerve that controls the external urethral sphincter?
answers
1. chemical buffers, kidneys, lungs.
2. bicarbonate
3. expiration of CO2 reduces acidity.
4. excess H+ ions are excreted, bound to phosphate and other buffers.
5. a pH below 7.0 results in a depressed CNS state- leading to coma and death. a pH above 7.8 results in an overactive CNS: leading to nervousness, muscle tetany, convulsions.
6. CO2 is derived from metabolism and is a volatile source of acidity. phosphoric, sulfuric, and hydrochloric acids are non volatile sources of acids and are derived from nucleic acid/protein/amino acid metabolism.
7. bicarbonate to carbon dioxide.
8. carbonic anhydrase.
9. pKa of bicarbonate is 6.1- at the body's pH of 7.4, CO2 is constantly removed.
10. because the basic bicarbonate is being selectively reabsorbed to maintain the buffer system, and the excess H+ from the dietary acid loads are being filtered and excreted.
11. metabolism produces CO2. H+ from non volatile acids can also combine with bicarbonate and create CO2.
12. CO2 combines with water to form carbonic acid, which dissociates into bicarbonate and H+ ion. in the kidney, H+ is secreted and bicarbonate is reabsorbed.
13. hydrogen ion is secreted into the lumen, where it combines with bicarbonate to form carbonic acid, which is converted to CO2 and H2O by carbonic anhydrase. CO2 then diffuses through the epithelial membrane and reforms bicarbonate, which is then reabsorbed into circulation.
14. when there is an acid load, there is more H+ than the level of bicarbonate- excess H+ is bound to ammonia and phosphate and excreted. (any excess bicarbonate is simply excreted)
15. bicarbonate has been mostly reabsorbed in the proximal tubules, so H+ is simply secreted by the ATPase pumps in the intercalated cells and lowers the pH of the lumen to approximately 4.5.
16. the phosphate buffer combines with excess H+ secreted into the lumen and aids in its excretion.
17. the ammonia buffer system.
18. glutamine in proximal convoluted tubule
19. ammonia combines with H+ in the proximal tubule, and is reabsorbed in the thick ascending limb, and is then secreted back into the tubule at the distal convoluted tubule and the collecting duct.
20. each H+ ion that is secreted, buffered, and excreted is dissociated from carbonic acid, forming bicarbonate which can then reenter circulation.
21. low blood potassium levels pull K+ ions out via a K+/H+ antiporter, thereby pulling in H+ ions which are then secreted into the urine.
22. angiotensin II stimulates the PCT Na/H contransporters, which facilitate Na reabsorption and H secretion.
23. aldosterone stimulates the intercalated cell secretion of H+, stimulates the Na/H antiporter, and upregulates the Na/K pump (thereby stimulating the Na/H antiporter)
24. the excess H+ that is produced by excess CO2 in the body is secreted and bound to ammonia and phosphate buffers and excreted, thereby raising pH. every H+ ion that is excreted also corresponds to a new bicarbonate ion which can be used to buffer the pH further.
25. less H+ is secreted, allowing excess bicarbonate to be excreted.
26. excess bicarbonate being lost through diarrhea, renal failure (H+ not being secreted fast enough), acidic ketone bodies created from diabetes mellitus, and lactic acid produced from anaerobic respiration.
27. H+ secretion and bicarbonate addition in the kidneys, as well as hyperventilating reducing CO2 levels in the blood.
28. ingestion of antacids, excess H+ loss due to aldosterone or hypokalemia, or loss of HCl through vomiting.
29. less H+ is secreted, allowing excess bicarbonate to be excreted from the kidneys. hypoventilation also raises CO2 levels in the blood.
30. excess insoluble materials or water reabsorption causes stones to precipitate out.
31. calcium oxalate, due to both high calcium levels (from intestinal hyperabsorption or defective renal absorption) and high oxalate levels (intestinal over-absorption)
32. MgNH4PO4, caused by urease action of bacterial infection.
33. detrusor muscle.
34. the triangular area in the bladder between the two ureteric orifices and the urethral opening.
35. the prostate.
36. 20cm in males, 4 cm in females
37. internal urethral sphincter is involuntary, smooth muscle, controlled by autonomic nervous system, and relaxes when bladder is expanded. exteral sphincter is voluntary, striated muscle, controlled by pudendal nerve.
38. sympathetic nervous system
39. relaxation of detrusor muscle and constriction of internal urethral sphincter.
40. parasympathetic micturition reflexes- alternating detrusor contraction and relaxation along with internal urethral sphincter relaxation.
41. pudendal (S2,3,4)
body pH is largely determined by the balance between the acidic carbon dioxide and the basic bicarbonate. recall from respiratory physiology that carbon dioxide combines with water in cells via carbonic anhydrase to form carbonic acid, which then dissociates into bicarbonate and H+. the body can develop alkalosis or acidosis due to an imbalance of these molecules; acidosis can occur either by hypoventilation (retaining too much CO2) or through metabolic pathways- loss of bicarbonate through diarrhea, renal failure, buildup of lactic acid from exercise, excess ketone body production in the case of diabetes mellitus. alkalosis can occur by hyperventilation (loss of too much CO2 from lungs) or by ingestion of antacids, excess secretion of H+ in the kidneys due to hypertension, or vomiting of acidic HCl.
in order to regulate the pH, the body can increase or decrease the ventilation rate to regulate blood CO2 levels. another main source of pH regulation is in the kidneys via the balance between reabsorption and excretion of bicarbonate and H+. bicarbonate in the blood is filtered in the kidneys and combines with H+ secreted by the epithelial cells of the proximal tubule. this forms carbonic acid, which can be converted back into CO2 and H2O via carbonic anhydrase. the CO2 then diffuses back into the epithelial cells, where it reforms bicarbonate and H+ through the reverse reaction. in this way 99% of bicarbonate filtered through the kidney is reabsorbed.
if the acidity in the blood is too high, then H+ secreted into the lumen will be higher than the bicarbonate in the filtrate, and excess H+ will be bound to ammonia and phosphate buffers and excreted, raising the pH. conversely, if the blood is basic, then there will be more bicarbonate than H+, and the excess will be unable to be reabsorbed as CO2 and thus be excreted, lowering the pH. angiotensin II and aldosterone can both cause excess H+ secretion, resulting in low pH- angiotensin II stimulates the PCT Na+/H+ cotransporters in the tubular epithelia, while aldosterone stimulates the Na+/H+ antiporter, as well as stimulating intercalated cell secretion of H+. this means that the high angiotensinII and aldosterone levels associated with hypertension also result in a lower pH.
a brief look at kidney stones: when there is excess insoluble material in the filtrate or excess water reabsorption, sometimes stones can develop in the kidney and block urine passage. the most common is the calcium oxalate stone, which develops from a hyper-reabsorption of calcium and oxalate from the intestines, which then combine in the kidneys. a second type of kidney stone is struvite, which forms from a bacterial enzyme, urease, which degrades urea into NH3, which raises pH and forms MgNH4PO4 stones.
the urine that forms in the kidney then goes out via the ureters into the bladder. the bladder is surrounded by the detrusor muscle, and has openings that lead out into the urethra, which leads out into the outside world. the urethral sphincter has two layers, the inner sphincter, which is controlled by parasympathetic smooth muscle, and the outer layer, which is controlled by voluntary striated muscle (pudendal nerve, S2,3,4). when the bladder is filling, the detrusor muscle relaxes and the inner sphincter contracts. during the micturition (urination) reflex, the detrusor muscle contracts and the inner sphincter relaxes.
questions
1. what is blood pH regulated by?
2. what is the main chemical buffer in the blood?
3. how do the lungs regulate pH?
4. how do the kidneys regulate pH?
5. what are the pH limits of the body and what occurs beyond the limits?
6. what are the sources of acidity in the body?
7. acidity depends on the ratio between...
8. the reaction that produces bicarbonate from CO2 is catalyzed by...
9. what is the pKa of bicarbonate and what happens at the physiologic pH of 7.4?
10. why is urine continuously acidified?
11. what are the two sources for production of CO2 in the body?
12. describe the ultimate fate of CO2.
13. describe the reabsorption of bicarbonate in the proximal convoluted tubules of the kidney.
14. describe the reabsorption of bicarbonate in the proximal convoluted tubules when there is an acid load.
15. describe acid secretion in the distal convoluted tubules.
16. what is the phosphate buffer? what does it do?
17. what is the major buffer system for excess H+ ions?
18. ammonium buffer produced from...
19. describe the path of the ammonium buffer through the nephron.
20. what is "bicarbonate addition"?
21. how do low potassium levels contribute to an acid urine?
22. what effect does angiotensin II have on H+ secretion?
23. what are the three ways in which aldosterone increases H+ secretion?
24. what is the body's response to respiratory acidosis?
25. what is the body's response to respiratory alkalosis?
26. what are four potential causes of metabolic acidosis?
27. what is the body's response to metabolic acidosis?
28. what are three potential causes of metabolic alkalosis?
29. what is the body's response to metabolic alkalosis?
30. what is the cause of kidney stones?
31. what is the most common type of kidney stone and what is it caused by?
32. what are struvite stones and how are they formed?
33. what is the muscle that contracts in the bladder?
34. what is the trigone?
35. in males, external and internal urethral sphincters are separated by...
36. how long is the urethra in males vs. females?
37. describe the difference between the internal vs. external urethral sphincters in females.
38. bladder filling is mediated by the...
39. baroreceptor sensory neurons in the bladder stimulates...
40. pressure waves are ...
41. what is the nerve that controls the external urethral sphincter?
answers
1. chemical buffers, kidneys, lungs.
2. bicarbonate
3. expiration of CO2 reduces acidity.
4. excess H+ ions are excreted, bound to phosphate and other buffers.
5. a pH below 7.0 results in a depressed CNS state- leading to coma and death. a pH above 7.8 results in an overactive CNS: leading to nervousness, muscle tetany, convulsions.
6. CO2 is derived from metabolism and is a volatile source of acidity. phosphoric, sulfuric, and hydrochloric acids are non volatile sources of acids and are derived from nucleic acid/protein/amino acid metabolism.
7. bicarbonate to carbon dioxide.
8. carbonic anhydrase.
9. pKa of bicarbonate is 6.1- at the body's pH of 7.4, CO2 is constantly removed.
10. because the basic bicarbonate is being selectively reabsorbed to maintain the buffer system, and the excess H+ from the dietary acid loads are being filtered and excreted.
11. metabolism produces CO2. H+ from non volatile acids can also combine with bicarbonate and create CO2.
12. CO2 combines with water to form carbonic acid, which dissociates into bicarbonate and H+ ion. in the kidney, H+ is secreted and bicarbonate is reabsorbed.
13. hydrogen ion is secreted into the lumen, where it combines with bicarbonate to form carbonic acid, which is converted to CO2 and H2O by carbonic anhydrase. CO2 then diffuses through the epithelial membrane and reforms bicarbonate, which is then reabsorbed into circulation.
14. when there is an acid load, there is more H+ than the level of bicarbonate- excess H+ is bound to ammonia and phosphate and excreted. (any excess bicarbonate is simply excreted)
15. bicarbonate has been mostly reabsorbed in the proximal tubules, so H+ is simply secreted by the ATPase pumps in the intercalated cells and lowers the pH of the lumen to approximately 4.5.
16. the phosphate buffer combines with excess H+ secreted into the lumen and aids in its excretion.
17. the ammonia buffer system.
18. glutamine in proximal convoluted tubule
19. ammonia combines with H+ in the proximal tubule, and is reabsorbed in the thick ascending limb, and is then secreted back into the tubule at the distal convoluted tubule and the collecting duct.
20. each H+ ion that is secreted, buffered, and excreted is dissociated from carbonic acid, forming bicarbonate which can then reenter circulation.
21. low blood potassium levels pull K+ ions out via a K+/H+ antiporter, thereby pulling in H+ ions which are then secreted into the urine.
22. angiotensin II stimulates the PCT Na/H contransporters, which facilitate Na reabsorption and H secretion.
23. aldosterone stimulates the intercalated cell secretion of H+, stimulates the Na/H antiporter, and upregulates the Na/K pump (thereby stimulating the Na/H antiporter)
24. the excess H+ that is produced by excess CO2 in the body is secreted and bound to ammonia and phosphate buffers and excreted, thereby raising pH. every H+ ion that is excreted also corresponds to a new bicarbonate ion which can be used to buffer the pH further.
25. less H+ is secreted, allowing excess bicarbonate to be excreted.
26. excess bicarbonate being lost through diarrhea, renal failure (H+ not being secreted fast enough), acidic ketone bodies created from diabetes mellitus, and lactic acid produced from anaerobic respiration.
27. H+ secretion and bicarbonate addition in the kidneys, as well as hyperventilating reducing CO2 levels in the blood.
28. ingestion of antacids, excess H+ loss due to aldosterone or hypokalemia, or loss of HCl through vomiting.
29. less H+ is secreted, allowing excess bicarbonate to be excreted from the kidneys. hypoventilation also raises CO2 levels in the blood.
30. excess insoluble materials or water reabsorption causes stones to precipitate out.
31. calcium oxalate, due to both high calcium levels (from intestinal hyperabsorption or defective renal absorption) and high oxalate levels (intestinal over-absorption)
32. MgNH4PO4, caused by urease action of bacterial infection.
33. detrusor muscle.
34. the triangular area in the bladder between the two ureteric orifices and the urethral opening.
35. the prostate.
36. 20cm in males, 4 cm in females
37. internal urethral sphincter is involuntary, smooth muscle, controlled by autonomic nervous system, and relaxes when bladder is expanded. exteral sphincter is voluntary, striated muscle, controlled by pudendal nerve.
38. sympathetic nervous system
39. relaxation of detrusor muscle and constriction of internal urethral sphincter.
40. parasympathetic micturition reflexes- alternating detrusor contraction and relaxation along with internal urethral sphincter relaxation.
41. pudendal (S2,3,4)
Monday, February 2, 2009
organ systems: calcium and phosphate
this is the 5th lecture in the series on the kidney and talks about the kidneys' role in the regulation of calcium and phosphate levels. the kidney is one of three regulatory sites for calcium blood levels, the other two being the intestine and the bone. falling blood calcium levels trigger the release of parathyroid hormone from the parathyroid glands, which has a multifaceted effect that ultimately raises blood calcium levels.
in the kidney, the 60% of calcium that is filtered (meaning not bound to blood proteins) is mainly reabsorbed in the proximal convoluted tubule in a fashion similar to the reabsorption of sodium. PTH regulation plays a role in the reabsorption of calcium in the thick ascending limb and distal convoluted tubule; by upregulating calcium channels and pumps in the tubular epithelium. it also downregulates phosphate transporters, leading to the simultaneous decreasing of phosphate reabsorption. the rationale behind this is that high phosphate levels and calcium levels would lead to mineralization in non-bone tissues.
in the intestines, PTH stimulates calcium absorption from the gut by way of regulating the synthesis of vitamin D into its active form. vitamin D then activates calcium channels and calbindin, which transports calcium across the cells.
in the bones, PTH regulates blood calcium levels by maintaining the balance between calcium being deposited onto new bone surfaces by osteoblasts (deposition) vs. calcium being released into the bloodstream by the breakdown of bone by osteoclasts (resorption). in general, PTH stimulates osteoclast activity by signalling apoptosis in osteoblasts, thereby raising calcium levels. if PTH is pulsed, however, osteoblast apoptosis is inhibited and deposition by osteoblasts can actually be stimulated.
a few pathologies related to calcium regulation: hyperparathyroidism results in the excess secretion of PTH and thus excessively high blood Ca2+ levels, as well as a loss of calcium levels in the bone. hypoparathyroidism is the opposite condition which results in low blood calcium levels. osteomalacia is a demineralization of the bone which results from a deficiency of calcium or vitamin D. osteoporosis is also a demineralization of the bone which results in the loss of bone matrix, not just calcium.
questions
1. what are calcium and phosphate used for in the body?
2. how closely regulated are calcium levels in the body?
3. where are the main sites for homeostatic control of calcium levels?
4. what are the primary hormones that provide homeostatic maintenance of calcium and phosphate levels?
5. what form is calcium found in the body? how much is filtered in the kidney?
6. how does acidosis relate to Ca2+ in the blood? what does it result in?
7. how does alkalosis relate to Ca2+ in the blood? what does it result in?
8. PTH is secreted in response to...
9. describe the reabsorption of Ca2+ in the kidney.
10. describe PTH's control over phosphate reabsorption.
11. why does PTH stimulate reabsorption of Ca2+ and simultaneous excretion of PO4-?
12. describe vitamin D's role in intestinal calcium absorption.
13. describe PTH's role in vitamin D synthesis.
14. describe vitamin D's role in intestinal phosphate absorption.
15. what are the two factors that regulate bone formation and remodeling?
16. describe how stress regulates remodeling of bone.
17. calcium and phosphate are stored in bone in the form of...
18. how is hydroxyapetite formation inhibited in non bone tissues?
19. how do osteoblasts overcome the solubilizing of calcium and phosphate by pyrophosphate in bone?
20. what is calcitonin and where is it released from?
21. how does calcitonin lower blood Ca+ levels?
22. how does PTH stimulate deposition of bone?
23. how does PTH stimulate resorption of bone?
24. how is PTH used to control the balance between deposition/resorption of bone?
25. what effect does hyperparathyroidism have on Ca2+ levels?
26. what effect does hypoparathyroidism have on Ca2+ levels?
27. osteomalacia is...
28. osteoporosis is...
answers
1. muscle contraction, secretion of neurotransmitters, hormones, enzymes, etc.
2. very closely, varying only 1-2% daily or weekly
3. kidney, bone, intestines
4. parathyroid hormone, vitamin D, calcitonin
5. 40% protein bound (and thus not filterable by the kidney), 10% in Ca2+ form, 50% bound to anions. 60% filtered in the kidney.
6. H+ compete with Ca2+ for sites on albumin, which transports the ions in the blood. if the pH is low, then there is less protein bound calcium and thus more free ionized form. this causes decreased neural activity and muscle weakness.
7. if there are less H+ in the blood, then Ca2+ binds to proteins in the blood and reduces the free ionized form. this causes neuromuscular irritability and CNS problems.
8. a fall in blood Ca2+ level.
9. 2/3 of the Ca2+ is reabsorbed in the proximal convoluted tubule, and 1/3 is reabsorbed in the thick ascending loop and distal convoluted tubule. PTH provides fine control over Ca2+ reabsorption in the ascending loop and distal convoluted tubule.
10. PTH inhibits reabsorption of phosphate in the proximal convoluted tubule, where most phosphate reabsorption takes place.
11. because raising both phosphate and calcium levels could create calcium phosphate in soft tissues.
12. vitamin D upregulates of calcium membrane transporters as well as calbindin, which carries calcium across the cell.
13. PTH, secreted in response to falling Ca2+ levels, regulates the synthesis of 1,25 hydroxylated vitamin D- the active form.
14. vitamin D upregulates Na-PO4 cotransporter in intestinal cells.
15. hormones and physical stress.
16. stress creates a piezoelectric effect that initiates osteoblast (bone building) and osteoclast (bone destroying) activity on opposing surfaces which remodels bone.
17. hydroxyapetite: Ca10(PO4)6OH2
18. it remains in soluble form by pyrophosphate.
19. osteoblasts contain alkaline phosphatases that cleave pyrophosphates, freeing calcium and phosphate to form bone.
20. a hormone that is released in response to rising Ca2+ levels that counters the effects of PTH. released from parafollicular cells of the thyroid.
21. by inhibiting osteoclast activity; free Ca2+ is then used to deposit bone by osteoblasts.
22. PTH stimulates osteoclast activity, which can induce release of growth factors from bone matrix which can in turn stimulate osteoblast deposition of bone.
23. PTH stimulates osteoblast to initiate RANK/RANKL paracrines which activates osteoclasts and thus stimulates bone resorption.
24. if PTH is secreted intermittently, osteoblast apoptosis is inhibited and deposition occurs. if PTH is secreted continuously, osteoblasts continue to undergo apoptosis and osteoclast activity resorbs bone.
25. excess secretion of PTH causes blood Ca2+ levels to rise and bone density to fall.
26. reduction in osteoclastic activity reduces resorption of calcium and lowers blood calcium levels.
27. demineralization of bone resulting from deficiency in calcium or vitamin D.
28. loss of bone matrix
in the kidney, the 60% of calcium that is filtered (meaning not bound to blood proteins) is mainly reabsorbed in the proximal convoluted tubule in a fashion similar to the reabsorption of sodium. PTH regulation plays a role in the reabsorption of calcium in the thick ascending limb and distal convoluted tubule; by upregulating calcium channels and pumps in the tubular epithelium. it also downregulates phosphate transporters, leading to the simultaneous decreasing of phosphate reabsorption. the rationale behind this is that high phosphate levels and calcium levels would lead to mineralization in non-bone tissues.
in the intestines, PTH stimulates calcium absorption from the gut by way of regulating the synthesis of vitamin D into its active form. vitamin D then activates calcium channels and calbindin, which transports calcium across the cells.
in the bones, PTH regulates blood calcium levels by maintaining the balance between calcium being deposited onto new bone surfaces by osteoblasts (deposition) vs. calcium being released into the bloodstream by the breakdown of bone by osteoclasts (resorption). in general, PTH stimulates osteoclast activity by signalling apoptosis in osteoblasts, thereby raising calcium levels. if PTH is pulsed, however, osteoblast apoptosis is inhibited and deposition by osteoblasts can actually be stimulated.
a few pathologies related to calcium regulation: hyperparathyroidism results in the excess secretion of PTH and thus excessively high blood Ca2+ levels, as well as a loss of calcium levels in the bone. hypoparathyroidism is the opposite condition which results in low blood calcium levels. osteomalacia is a demineralization of the bone which results from a deficiency of calcium or vitamin D. osteoporosis is also a demineralization of the bone which results in the loss of bone matrix, not just calcium.
questions
1. what are calcium and phosphate used for in the body?
2. how closely regulated are calcium levels in the body?
3. where are the main sites for homeostatic control of calcium levels?
4. what are the primary hormones that provide homeostatic maintenance of calcium and phosphate levels?
5. what form is calcium found in the body? how much is filtered in the kidney?
6. how does acidosis relate to Ca2+ in the blood? what does it result in?
7. how does alkalosis relate to Ca2+ in the blood? what does it result in?
8. PTH is secreted in response to...
9. describe the reabsorption of Ca2+ in the kidney.
10. describe PTH's control over phosphate reabsorption.
11. why does PTH stimulate reabsorption of Ca2+ and simultaneous excretion of PO4-?
12. describe vitamin D's role in intestinal calcium absorption.
13. describe PTH's role in vitamin D synthesis.
14. describe vitamin D's role in intestinal phosphate absorption.
15. what are the two factors that regulate bone formation and remodeling?
16. describe how stress regulates remodeling of bone.
17. calcium and phosphate are stored in bone in the form of...
18. how is hydroxyapetite formation inhibited in non bone tissues?
19. how do osteoblasts overcome the solubilizing of calcium and phosphate by pyrophosphate in bone?
20. what is calcitonin and where is it released from?
21. how does calcitonin lower blood Ca+ levels?
22. how does PTH stimulate deposition of bone?
23. how does PTH stimulate resorption of bone?
24. how is PTH used to control the balance between deposition/resorption of bone?
25. what effect does hyperparathyroidism have on Ca2+ levels?
26. what effect does hypoparathyroidism have on Ca2+ levels?
27. osteomalacia is...
28. osteoporosis is...
answers
1. muscle contraction, secretion of neurotransmitters, hormones, enzymes, etc.
2. very closely, varying only 1-2% daily or weekly
3. kidney, bone, intestines
4. parathyroid hormone, vitamin D, calcitonin
5. 40% protein bound (and thus not filterable by the kidney), 10% in Ca2+ form, 50% bound to anions. 60% filtered in the kidney.
6. H+ compete with Ca2+ for sites on albumin, which transports the ions in the blood. if the pH is low, then there is less protein bound calcium and thus more free ionized form. this causes decreased neural activity and muscle weakness.
7. if there are less H+ in the blood, then Ca2+ binds to proteins in the blood and reduces the free ionized form. this causes neuromuscular irritability and CNS problems.
8. a fall in blood Ca2+ level.
9. 2/3 of the Ca2+ is reabsorbed in the proximal convoluted tubule, and 1/3 is reabsorbed in the thick ascending loop and distal convoluted tubule. PTH provides fine control over Ca2+ reabsorption in the ascending loop and distal convoluted tubule.
10. PTH inhibits reabsorption of phosphate in the proximal convoluted tubule, where most phosphate reabsorption takes place.
11. because raising both phosphate and calcium levels could create calcium phosphate in soft tissues.
12. vitamin D upregulates of calcium membrane transporters as well as calbindin, which carries calcium across the cell.
13. PTH, secreted in response to falling Ca2+ levels, regulates the synthesis of 1,25 hydroxylated vitamin D- the active form.
14. vitamin D upregulates Na-PO4 cotransporter in intestinal cells.
15. hormones and physical stress.
16. stress creates a piezoelectric effect that initiates osteoblast (bone building) and osteoclast (bone destroying) activity on opposing surfaces which remodels bone.
17. hydroxyapetite: Ca10(PO4)6OH2
18. it remains in soluble form by pyrophosphate.
19. osteoblasts contain alkaline phosphatases that cleave pyrophosphates, freeing calcium and phosphate to form bone.
20. a hormone that is released in response to rising Ca2+ levels that counters the effects of PTH. released from parafollicular cells of the thyroid.
21. by inhibiting osteoclast activity; free Ca2+ is then used to deposit bone by osteoblasts.
22. PTH stimulates osteoclast activity, which can induce release of growth factors from bone matrix which can in turn stimulate osteoblast deposition of bone.
23. PTH stimulates osteoblast to initiate RANK/RANKL paracrines which activates osteoclasts and thus stimulates bone resorption.
24. if PTH is secreted intermittently, osteoblast apoptosis is inhibited and deposition occurs. if PTH is secreted continuously, osteoblasts continue to undergo apoptosis and osteoclast activity resorbs bone.
25. excess secretion of PTH causes blood Ca2+ levels to rise and bone density to fall.
26. reduction in osteoclastic activity reduces resorption of calcium and lowers blood calcium levels.
27. demineralization of bone resulting from deficiency in calcium or vitamin D.
28. loss of bone matrix
Sunday, February 1, 2009
organ systems: blood pressure regulation, potassium, diuretics
this unit talks about the different mechanisms used by the kidney to maintain blood pressure. in contrast to the short term regulation of blood pressure, which occurs in seconds or minutes when the baroreceptors in the aortic and carotid sinuses trigger a sympathetic pathway that increases cardiac output and decreases total peripherial resistance (recall from the vascular regulation lecture), the long term regulation of blood pressure occurs on the order of days to weeks and involves stimulation and inhibition of hormone systems which regulate fluid excretion in the kidney.
two conditions that are subject to regulation by the kidney are introduced: hypervolemia and hypovolemia. hypovolemia is the loss of body fluids via hemorrhage, dehydration, etc.; this is reflected in a decreased blood volume, which is sensed at both the cardiac baroreceptor level and also at the JGA apparatus. the sympathetic nervous response is to constrict the afferent and efferent arterioles (as well as ADH release in extreme cases), while JGA stimulates the renin-angiotensin system, the net effect being increased reabsorption. congestive heart failure or aortic stenosis can incorrectly stimulate a correction for hypovolemia: the decreased blood flow in these conditions will result in the JGA responding as if there is hypovolemia and cause excess reabsorption, leading to systemic edema. hypervolemia is the opposite condition in which there is excess fluid volume (due to fluid or salt intake). the body's response to this is to inhibit the renin-angiotensin system, and activate atrial natriuretic peptides, as well as pressure natriuresis. all three of these responses entail mechanisms that increase excretion and decrease reabsorption.
the next section talks about hypertension, which is essentially a chronically high blood pressure, and what it is caused by. "primary" hypertension seen in 90% of all cases of high blood pressure and usually involves the "blunted pressure natriuresis" phenomenon. pressure natriuresis is normally an increase in the excretion of water and solute in response to increased arterial pressure via a dilation of the vasa recta, which shifts the starling forces in a direction that inhibits reabsorption. excess angiotensin II and salt can oxidatively damage the vasa recta, not allowing it to vasodilate as easily; this means that the pressure natriuresis compensation begins at a higher pressure than usual (displayed a shifting right of the solute excreted vs. arterial pressure curve). secondary hypertension can be caused by a variety of conditions such as renovascular hypertension or renal parenchymal disease, the end result being salt retention and a rightward shifting of the pressure natriuresis curve. in salt-sensitive individuals with hypertension, increasing salt intake can further increase the pressure at which pressure natriuresis begins, due to the damage to the vasa recta and peripheral tissues that occurs in these individuals.
the progression of hypertension can be divided into three phases: phase I is characterized by a persistent excess of angiotensin II and sympathetic activity. phase II is characterized by the chronic vasoconstriction resulting from high angiotensin II, which begins to cause subtle renal injury and an increase in blood pressure/volume. phase III is when the pressure natriuresis occurs, lowering the blood pressure back down to normal, but resulting in a hypertensive kidney.
the next section looks at the regulation of the reabsorption of K+ in the kidney. control over K+ is important because most of the K+ in the body is intracellular, rather than in the extra cellular fluid- thus small changes in intake or excretion of potassium can have large effects. Most of the K+ reabsorption happens in the proximal tubules and is not controlled by hormone or ion levels. However, in the collecting duct, potassium reabsorption can depend on relative ion levels (the alpha-intercalated cells excrete H+ in exchange for K+ in response to a K+ deficiency) or hormone levels (the principal cells have sodium / potassium pumps that are upregulated by aldosterone)
the last section looks at diuretics, which are substances that increase urine output generally by blocking sodium reabsorption in different parts of the nephron, or by increasing the osmolality of the fluid in the lumen of the tubule (and therefore holding the water in the lumen to be excreted). osmotic diuretics such as glucose or sucrose increase osmotic retention in the proximal tubule, and also increase K+ secretion in the distal tubule due to the larger concentration gradient between the lumen and the interstitial space. loop diuretics block solute reabsorption in the thick ascending tubule and therefore osmotically pulls more water into the lumen to be excreted. thiazide is another diuretic that has the same effect on the distal convoluted tubule. caffiene is a diuretic that blocks reabsorption in both the proximal and distal tubule. all of these diuretics mentioned thus far have the potential to induce hypokalemia, a deficiency of potassium, because the hypovolemia that could develop might trigger aldosterone release, which would increase K+ excretion. a "potassium sparing" diuretic is an aldosterone inhibitor, which simply blocks the action of the sodium/potassium pump in the principal cells, leaving sodium in the lumen which increases osmolality and pulls water to be excreted.
questions
1. blood pressure is a measure of how effectively...
2. three factors that are needed to maintain adequate blood pressure...
3. blood volume is regulated by...
4. describe short term regulation of blood pressure.
5. describe long term regulation of blood pressure.
6. what is the timescale for the short term regulation of blood pressure?
7. what is the timescale for the long term regulation of blood pressure?
8. how is blood volume monitored?
9. what is the body's response to hypovolemia?
10. how can congestive heart failure or stenosis of the arteries lead to pulmonary edema?
11. what is the body's response to hypervolemia?
12. what is the difference between the response of the JGA and ANP/pressure natriuresis to hypervolemia?
13. describe what happens when pressure natriuresis is "blunted".
14. most cases of primary hypertension are due to...
15. most cases of secondary hypertension are due to...
16. what occurs in renovascular hypertension?
17. what occurs in salt-sensitive hypertension?
18. how does the pressure natriuresis curve shift in salt sensitive hypertension?
19. describe the two factors that affect the vascular tone of the vasa recta.
20. what effect do angiotensin II and salt have on the vasa recta?
21. what are the two ways in which damage to the vasa recta can augment vasoconstriction?
22. what are some other risk factors for hypertension?
23. what are the characteristics of phase 1 of primary hypertension?
24. what are the characteristics of phase 2 of primary hypertension?
25. what are the characteristics of phase 3 of primary hypertension?
26. what are hypo and hyperkalemia and how does the body respond to these conditions?
27. describe the reabsorption of potassium in the proximal tubules.
28. where is reabsorption of potassium hormonally regulated?
29. what are alpha-intercalated cells and what do they do?
30. what are principal cells and what role do they play in the regulation of reabsorption of potassium?
31. how does excess and deficient K+ affect the principal cells?
32. how do diuretics work?
33. how does heart failure lead to edema?
34. how do osmotic diuretics work?
35. most common treatment of hypertension is...
36. what does thiazide do?
37. describe the mechanism of the treatment of hypertension with thiazide and ACE inhibitor.
38. what do loop diuretics do and what are some examples of them?
39. caffeine causes diuresis by...
40. why is an aldosterone inhibiting diuretic called a potassium sparing diuretic?
answers
1. the vascular system perfuses organs with blood.
2. integrity/strength of vessels, compliance of blood vessels, and adequate blood volume (5L)
3. cardiac output, peripheral resistance,
4. baroreceptors sense changes in mean arterial pressure and adjust cardiac output and total peripheral resistance accordingly.
5. baroreceptors and salt detectors initiate neuroendocrine response that can adjust blood volume (and therefore blood pressure) by altering reabsorption of fluid in kidney.
6. response within seconds and can last for minutes.
7. days to weeks.
8. via baroreceptors in arteries, veins, as well as the juxtaglomerular apparatus.
9. baroreceptors and JGA cells trigger renin / angiotensin system which increases reabsorption, and in severe cases the CNS is triggered to release ADH which also increases reabsorption.
10. both of these conditions lead to a decrease in blood flow to the kidney, which triggers mechanisms that increase reabsorption, increasing fluid volume excessively and causing circulatory congestion and pulmonary edema.
11. inhibiting the RAAS system, production of atrial natriuretic peptides, and stimulating pressure natriuresis.
12. JGA involved mainly in suppressing renin-angiotensin system, which then decreases reabsorption. ANP/pressure natriuresis is more involved in increasing GFR (but still subject to glomerulotubular feedback)
13. blunted pressure natriuresis can be caused by damage to the vasa recta that reduces its ability to synthesize NO. this leads to higher blood pressures required to produce the same vasodilation, effectively reducing excretion and shifting the pressure natriuresis curve (sodium excretion vs. blood pressure) to the right.
14. high blood pressure, and blunted pressure natriuresis.
15. renal diseases that result in salt retention such as renal parenchymal disease, renovascular disease, pheochromocytoma, cushing syndrome.
16. hardening of the renal arteries decreases renal blood flow, eliciting the RAAS system and secretion of angiotensin II which constricts the arteries and shifts the pressure natriuresis curve to the right.
17. increased salt intake in salt-sensitive individuals causes short term increases in blood pressure.
18. the curve shifts to the right and the slope decreases.
19. angiotensin II released by local vessels and tubules cause pericytes around vasa recta to constrict by increasing intracellular levels of Ca2+. NO produced by thick ascending loop causes pericytes to relax.
20. creating reactive oxygen species that damage vasa recta via oxidative stress.
21. by exacerbating RAAS vasoconstriction and inhibiting vasodilation by NO, prostaglandins, dopamine.
22. genetics, age, obesity, insulin resistance
23. persistent excess angiotensin II and sympathetic nervous activity.
24. chronic vasoconstriction due to the angiotensin/NO balance lead to subtle renal injury which leads to sodium retention and increased blood volume/pressure.
25. pressure natriuresis curve shifts to the right; blood pressure rises and salt excretion increases.
26. hypokalemia is a deficiency of potassium which causes muscle weakness and twitches, and is compensated by increased K+ reabsorption. hyperkalemia is excess potassium which causes cardiac arrhythmias and excitability; compensated by increased K+ secretion.
27. 67% of potassium is reabsorbed in proximal tubules, 20% in thick ascending limbs. neither of these areas are regulated by hormone or ion levels.
28. in the distal tubule and collecting duct
29. cells in the collecting duct that actively reabsorb K+ via a K+/H+ ATPase pump.
30. principal cells make up 90% of the collecting duct epithelium and contain ATPase pumps that exchange K+ for Na+. aldosterone can upregulate these pumps, which increases Na+ and therefore water reabsorption, as well as increasing K+ excretion.
31. in K+ excess, ATPase pumps in principal cells are upregulated to increase excretion of K+. in K+ deficiency, aldosterone release is inhibited, causing more K+ to be retained within the body.
32. by inhibiting sodium reabsorptions at different points along the nephritic tubule.
33. heart failure causes a drop in arterial pressure which via the RAAS system induces higher fluid reabsorption in the kidney, causing a higher venous pressure. higher venous hydrostatic pressure causes fluid to leak out into the extracellular space, causing edema.
34. solutes such as glucose, sucrose, mannitol, corn silk, are filtered but not reabsorbed, leading to a higher solute concentration in the tubule and thus less reabsorption of water.
35. thiazide diuretics and ACE inhibitor
36. inhibits Na,Cl reabsorption in distal tubules leading to more water excretion
37. thiazide blocks the Na,Cl reabsorption in the distal tubules, leading to more water excretion. this could in theory produce a hypovolumic state, which would trigger aldosterone release and therefore K+ excretion. thus ACE inhibitors are used to block the formation of angiotensin II and counter K+ secretion.
38. loop diuretics block reabsorption of Na, Cl, K in the ascending loop of henle and thus increase water excretion. examples are: Lasix, ethacrynic acid, bumetanide.
39. inhibiting Na+ reabsorption from proximal and distal tubules.
40. it inhibits aldosterone release, which increases Na+ excretion in the water and retains more K+.
two conditions that are subject to regulation by the kidney are introduced: hypervolemia and hypovolemia. hypovolemia is the loss of body fluids via hemorrhage, dehydration, etc.; this is reflected in a decreased blood volume, which is sensed at both the cardiac baroreceptor level and also at the JGA apparatus. the sympathetic nervous response is to constrict the afferent and efferent arterioles (as well as ADH release in extreme cases), while JGA stimulates the renin-angiotensin system, the net effect being increased reabsorption. congestive heart failure or aortic stenosis can incorrectly stimulate a correction for hypovolemia: the decreased blood flow in these conditions will result in the JGA responding as if there is hypovolemia and cause excess reabsorption, leading to systemic edema. hypervolemia is the opposite condition in which there is excess fluid volume (due to fluid or salt intake). the body's response to this is to inhibit the renin-angiotensin system, and activate atrial natriuretic peptides, as well as pressure natriuresis. all three of these responses entail mechanisms that increase excretion and decrease reabsorption.
the next section talks about hypertension, which is essentially a chronically high blood pressure, and what it is caused by. "primary" hypertension seen in 90% of all cases of high blood pressure and usually involves the "blunted pressure natriuresis" phenomenon. pressure natriuresis is normally an increase in the excretion of water and solute in response to increased arterial pressure via a dilation of the vasa recta, which shifts the starling forces in a direction that inhibits reabsorption. excess angiotensin II and salt can oxidatively damage the vasa recta, not allowing it to vasodilate as easily; this means that the pressure natriuresis compensation begins at a higher pressure than usual (displayed a shifting right of the solute excreted vs. arterial pressure curve). secondary hypertension can be caused by a variety of conditions such as renovascular hypertension or renal parenchymal disease, the end result being salt retention and a rightward shifting of the pressure natriuresis curve. in salt-sensitive individuals with hypertension, increasing salt intake can further increase the pressure at which pressure natriuresis begins, due to the damage to the vasa recta and peripheral tissues that occurs in these individuals.
the progression of hypertension can be divided into three phases: phase I is characterized by a persistent excess of angiotensin II and sympathetic activity. phase II is characterized by the chronic vasoconstriction resulting from high angiotensin II, which begins to cause subtle renal injury and an increase in blood pressure/volume. phase III is when the pressure natriuresis occurs, lowering the blood pressure back down to normal, but resulting in a hypertensive kidney.
the next section looks at the regulation of the reabsorption of K+ in the kidney. control over K+ is important because most of the K+ in the body is intracellular, rather than in the extra cellular fluid- thus small changes in intake or excretion of potassium can have large effects. Most of the K+ reabsorption happens in the proximal tubules and is not controlled by hormone or ion levels. However, in the collecting duct, potassium reabsorption can depend on relative ion levels (the alpha-intercalated cells excrete H+ in exchange for K+ in response to a K+ deficiency) or hormone levels (the principal cells have sodium / potassium pumps that are upregulated by aldosterone)
the last section looks at diuretics, which are substances that increase urine output generally by blocking sodium reabsorption in different parts of the nephron, or by increasing the osmolality of the fluid in the lumen of the tubule (and therefore holding the water in the lumen to be excreted). osmotic diuretics such as glucose or sucrose increase osmotic retention in the proximal tubule, and also increase K+ secretion in the distal tubule due to the larger concentration gradient between the lumen and the interstitial space. loop diuretics block solute reabsorption in the thick ascending tubule and therefore osmotically pulls more water into the lumen to be excreted. thiazide is another diuretic that has the same effect on the distal convoluted tubule. caffiene is a diuretic that blocks reabsorption in both the proximal and distal tubule. all of these diuretics mentioned thus far have the potential to induce hypokalemia, a deficiency of potassium, because the hypovolemia that could develop might trigger aldosterone release, which would increase K+ excretion. a "potassium sparing" diuretic is an aldosterone inhibitor, which simply blocks the action of the sodium/potassium pump in the principal cells, leaving sodium in the lumen which increases osmolality and pulls water to be excreted.
questions
1. blood pressure is a measure of how effectively...
2. three factors that are needed to maintain adequate blood pressure...
3. blood volume is regulated by...
4. describe short term regulation of blood pressure.
5. describe long term regulation of blood pressure.
6. what is the timescale for the short term regulation of blood pressure?
7. what is the timescale for the long term regulation of blood pressure?
8. how is blood volume monitored?
9. what is the body's response to hypovolemia?
10. how can congestive heart failure or stenosis of the arteries lead to pulmonary edema?
11. what is the body's response to hypervolemia?
12. what is the difference between the response of the JGA and ANP/pressure natriuresis to hypervolemia?
13. describe what happens when pressure natriuresis is "blunted".
14. most cases of primary hypertension are due to...
15. most cases of secondary hypertension are due to...
16. what occurs in renovascular hypertension?
17. what occurs in salt-sensitive hypertension?
18. how does the pressure natriuresis curve shift in salt sensitive hypertension?
19. describe the two factors that affect the vascular tone of the vasa recta.
20. what effect do angiotensin II and salt have on the vasa recta?
21. what are the two ways in which damage to the vasa recta can augment vasoconstriction?
22. what are some other risk factors for hypertension?
23. what are the characteristics of phase 1 of primary hypertension?
24. what are the characteristics of phase 2 of primary hypertension?
25. what are the characteristics of phase 3 of primary hypertension?
26. what are hypo and hyperkalemia and how does the body respond to these conditions?
27. describe the reabsorption of potassium in the proximal tubules.
28. where is reabsorption of potassium hormonally regulated?
29. what are alpha-intercalated cells and what do they do?
30. what are principal cells and what role do they play in the regulation of reabsorption of potassium?
31. how does excess and deficient K+ affect the principal cells?
32. how do diuretics work?
33. how does heart failure lead to edema?
34. how do osmotic diuretics work?
35. most common treatment of hypertension is...
36. what does thiazide do?
37. describe the mechanism of the treatment of hypertension with thiazide and ACE inhibitor.
38. what do loop diuretics do and what are some examples of them?
39. caffeine causes diuresis by...
40. why is an aldosterone inhibiting diuretic called a potassium sparing diuretic?
answers
1. the vascular system perfuses organs with blood.
2. integrity/strength of vessels, compliance of blood vessels, and adequate blood volume (5L)
3. cardiac output, peripheral resistance,
4. baroreceptors sense changes in mean arterial pressure and adjust cardiac output and total peripheral resistance accordingly.
5. baroreceptors and salt detectors initiate neuroendocrine response that can adjust blood volume (and therefore blood pressure) by altering reabsorption of fluid in kidney.
6. response within seconds and can last for minutes.
7. days to weeks.
8. via baroreceptors in arteries, veins, as well as the juxtaglomerular apparatus.
9. baroreceptors and JGA cells trigger renin / angiotensin system which increases reabsorption, and in severe cases the CNS is triggered to release ADH which also increases reabsorption.
10. both of these conditions lead to a decrease in blood flow to the kidney, which triggers mechanisms that increase reabsorption, increasing fluid volume excessively and causing circulatory congestion and pulmonary edema.
11. inhibiting the RAAS system, production of atrial natriuretic peptides, and stimulating pressure natriuresis.
12. JGA involved mainly in suppressing renin-angiotensin system, which then decreases reabsorption. ANP/pressure natriuresis is more involved in increasing GFR (but still subject to glomerulotubular feedback)
13. blunted pressure natriuresis can be caused by damage to the vasa recta that reduces its ability to synthesize NO. this leads to higher blood pressures required to produce the same vasodilation, effectively reducing excretion and shifting the pressure natriuresis curve (sodium excretion vs. blood pressure) to the right.
14. high blood pressure, and blunted pressure natriuresis.
15. renal diseases that result in salt retention such as renal parenchymal disease, renovascular disease, pheochromocytoma, cushing syndrome.
16. hardening of the renal arteries decreases renal blood flow, eliciting the RAAS system and secretion of angiotensin II which constricts the arteries and shifts the pressure natriuresis curve to the right.
17. increased salt intake in salt-sensitive individuals causes short term increases in blood pressure.
18. the curve shifts to the right and the slope decreases.
19. angiotensin II released by local vessels and tubules cause pericytes around vasa recta to constrict by increasing intracellular levels of Ca2+. NO produced by thick ascending loop causes pericytes to relax.
20. creating reactive oxygen species that damage vasa recta via oxidative stress.
21. by exacerbating RAAS vasoconstriction and inhibiting vasodilation by NO, prostaglandins, dopamine.
22. genetics, age, obesity, insulin resistance
23. persistent excess angiotensin II and sympathetic nervous activity.
24. chronic vasoconstriction due to the angiotensin/NO balance lead to subtle renal injury which leads to sodium retention and increased blood volume/pressure.
25. pressure natriuresis curve shifts to the right; blood pressure rises and salt excretion increases.
26. hypokalemia is a deficiency of potassium which causes muscle weakness and twitches, and is compensated by increased K+ reabsorption. hyperkalemia is excess potassium which causes cardiac arrhythmias and excitability; compensated by increased K+ secretion.
27. 67% of potassium is reabsorbed in proximal tubules, 20% in thick ascending limbs. neither of these areas are regulated by hormone or ion levels.
28. in the distal tubule and collecting duct
29. cells in the collecting duct that actively reabsorb K+ via a K+/H+ ATPase pump.
30. principal cells make up 90% of the collecting duct epithelium and contain ATPase pumps that exchange K+ for Na+. aldosterone can upregulate these pumps, which increases Na+ and therefore water reabsorption, as well as increasing K+ excretion.
31. in K+ excess, ATPase pumps in principal cells are upregulated to increase excretion of K+. in K+ deficiency, aldosterone release is inhibited, causing more K+ to be retained within the body.
32. by inhibiting sodium reabsorptions at different points along the nephritic tubule.
33. heart failure causes a drop in arterial pressure which via the RAAS system induces higher fluid reabsorption in the kidney, causing a higher venous pressure. higher venous hydrostatic pressure causes fluid to leak out into the extracellular space, causing edema.
34. solutes such as glucose, sucrose, mannitol, corn silk, are filtered but not reabsorbed, leading to a higher solute concentration in the tubule and thus less reabsorption of water.
35. thiazide diuretics and ACE inhibitor
36. inhibits Na,Cl reabsorption in distal tubules leading to more water excretion
37. thiazide blocks the Na,Cl reabsorption in the distal tubules, leading to more water excretion. this could in theory produce a hypovolumic state, which would trigger aldosterone release and therefore K+ excretion. thus ACE inhibitors are used to block the formation of angiotensin II and counter K+ secretion.
38. loop diuretics block reabsorption of Na, Cl, K in the ascending loop of henle and thus increase water excretion. examples are: Lasix, ethacrynic acid, bumetanide.
39. inhibiting Na+ reabsorption from proximal and distal tubules.
40. it inhibits aldosterone release, which increases Na+ excretion in the water and retains more K+.
Sunday, January 18, 2009
organ systems: renal system part 4- volume and pressure regulation
this is the 4th lecture in the series of the kidney and the second on the topic of osmoregulation. the last lecture basically looked at the mechanics behind osmoregulation: varying the the "motivation" (the osmotic difference between the tubules and the hypertonic interstitium) and the "permission" (the permeability of the tubules to solute and water). this section looked at the actual neuroendocrine feedback mechanisms in place which regulate fluid volume in response to changes in blood pressure or other signals. the first section introduced the importance of homeostatically maintaining the glomerular filtration rate (the rate at which blood is filtered from the glomerulus into the tubule) and renal plasma flow (the amount of blood that actually flows into the glomerulus). if the RPF and by extension GFR are too high, there is a danger that important nutrients will be simply excreted and not reabsorbed due to the fast perfusion rate through the nephritic tubules. in the reverse case, with a slow GFR / RPF, there is the danger that unwanted solutes will be reabsorbed.
GFR and RPF are thus maintained homeostatically by several different mechanisms against sharp increases or decreases in blood fluid volume and pressure. tubuloglomerular feedback is one such mechanism in which the afferent arteriole is stimulated to constrict in response to elevated blood pressure via a pathway that involves the macula densa sensing more solute particles-- causing the GFR and RPF to decrease back to normal levels. "myogenic" regulation is another, more reflexive feedback mechanism in which blood pressure changes stimulate baroreceptors in the afferent arteriole, which then constricts or dilates, depending if the blood pressure rises or falls, respectively.
we then look at the regulation of reabsorption, which occurs through multiple mechanisms. the first one mentioned is that of starling forces: the balance between hydrostatic and oncotic pressure in the capillaries. the efferent arteriole constricts and causes a pressure gradient such that while the pressure in the afferent arteriole and glomerulus is 60mmHg, the pressure in the efferent arteriole and the capillaries is 20mmHg. this pressure drop aids reabsorption in two ways: it lowers the hydrostatic pressure (less fluid coming into the capillaries), and raises the oncotic pressure (the pressure drop causes more fluid to be filtered, leaving more solutes in the plasma in the capillaries). both of these changes support reabsorption of solutes.
the next few mechanisms are all different molecules / hormones that counter blood pressure drops / increase reabsorption via different mechanisms. angiotensin II is one such molecule, and is created in response to renin release: renin cleaves angiotensin I from angiotensinogen in the kidney and liver, which is then converted to angiotensin II via angiotensin converting enzyme (ACE) in the lungs. angiotensin II has several effects on the kidney which all increase reabsorption. first, it works directly and quickly on the proximal tubules, constricting both the afferent and efferent arterioles.
second, it stimulates the release of aldosterone from the adrenal cortex, which increases the reabsorption in the distal tubules. it does so by upregulating the amount of Na/K pumps and sodium channels in the tubular membrane, thereby facilitating sodium (and thus water, which osmotically follows) reabsorption. aldosterone is also secreted in response to high potassium levels, since upregulating the Na/K pumps would increase potassium excretion.
third, it stimulates the release of ADH from the hypothalamus, which increases the collecting duct's permeability to water and thus aids reabsorption. ADH can also be released in response to blood pressure drops via the sympathetic nervous system, but generally only in response to large fluid drops such as in the case of hemorrage. (ADH is described in greater detail in lecture 3). finally, angiotensin II elicits the thirst impulse in the hypothalamus, causing an increase of fluid volume.
the next mechanism for increasing reabsorption is via the sympathetic nervous system. this pathway starts at the baroreceptors in the aortic and carotid arch, which can sense a drop in blood volume/pressure, stimulating the hypothalamus, which then triggers sympathetic activity from the medulla and spinal cord, which ultimately stimulate constriction of the afferent and efferent arteriole (recall that this increases reabsorption as in the case of angiotensin II above). this pathway can also be triggered by emotional cues such as fright and can produce a response within seconds, whereas the renin/angiotensin response is more on the order of minutes.
we then look at the factors that have the opposite effect: increasing excretion and decreasing reabsorption, generally in response to an increase in fluid volume (ingesting large amounts of liquid), increased Na+ concentration (which causes increased retention of fluid) or increased blood pressure. the first mechanism is via the atrial natriuretic peptide, which is released from the granules of the atrial baroreceptor cells in response to elevated blood pressure. in the kidney, ANP dilates the afferent arteriole, increasing GFR, and also inhibits the release of the molecules mentioned above: angiotensin II, ADH, and aldosterone. "pressure natriuresis" is the other mechanism by which excretion can be increased, and is the process in which increased blood pressure causes increased excretion of solute and water. this is accomplished via two mechanisms: first, the sodium channels and Na/K pumps are downregulated and endocytos-ed in the proximal tubule, decreasing its ability to reabsorb. second, nitric oxide is released from the endothelium of the vasa recta, which causes it to vasodilate- this increases the hydrostatic pressure and decreases the oncotic pressure, which via starling forces decreases the capillaries' absorptive capacity.
questions
1. volume of blood and extracellular fluid is regulated by...
2. sodium reabsorption is regulated by...
3. describe what happens when the GFR deviates too low or high from the homeostatic condition.
4. what regulates RBF (renal blood flow) and GFR?
5. what is the usual problem regarding regulation of renal filtration?
6. describe the tubuloglomerular feedback mechanism when body fluid volume is increased.
7. what does the macula densa release that constricts the afferent arteriole?
8. describe the myogenic mechanism for regulating renal blood flow.
9. what is the pressure drop between the afferent arterioles and the vasa recta and what is it caused by?
10. why is the pressure drop necessary?
11. what is the filtration fraction and how is it derived?
12. what are the two conditions in the capillaries necessary for reabsorption?
13. describe how the efferent arteriole influences reabsorption.
14. what is glomerulotubular balance?
15. where is fine regulation of Na+ levels and extracellular volume is carried out by?
16. what are the neuroendocrine factors that increase reabsorption and decrease excretion?
17. where and in response to what is renin released in the nephron?
18. describe the production of angiotensin II.
19. what does angiotensin II do in the kidneys?
20. describe the actions of angiotensin II on the proximal tubules of the nephron.
21. describe the actions of angiotensin II on the distal tubules of the nephron.
22. how does Captopril work?
23. describe the effect of aldosterone on the the distal tubules.
24. aldosterone is a ... secreted by the ...
25. aldosterone is released in response to...
26. sympathetic reflexes are triggered by...
27. describe how baroreceptor stimulation can lead to sympathetic stimulation of arteriole and tubular cells.
28. describe how sympathetic activity facilitates reabsorption.
29. describe the response time of sympathetic stimulation vs. that of the neuroendocrine stimulation.
30. describe ADH's role in blood volume/pressure regulation.
31. what are the two factors that decrease reabsorption / increase excretion?
32. where is atrial natruretic peptide released from?
33. how does ANP increase excretion?
34. what is pressure natriuresis?
35. what is the mechanism that it uses?
36. what role does nitric oxide play in pressure natriuresis?
37. what is the pressure natriuresis equilibrium point?
38. what are the two factors that counterbalance each other in the vasoconstriction / vasodilation of the vasa recta?
answers
1. the amount of sodium that is excreted
2. neuroendocrine factors.
3. when GFR is too low, unwanted waste products might be reabsorbed. if GRF is too high, nutrients might be excreted.
4. changes in the resistance of the afferent arteriole.
5. renal failure, where a drop of blood pressure causes too significant a drop in the renal filtration rate.
6. increased body fluid volume increases GFR and RBF, which increases solute concentration in the tubule. macula densa senses increased solute concentration and stimulates afferent arteriole to constrict, which decreases GFR and RBF to normal levels.
7. adenosine.
8. the afferent arterioles have barorecptors that are stretched when blood pressure rises, causing them to constrict reflexively, thus lowering the RBF to a normal rate.
9. 60mmHg in the afferent arterioles and 20mmHg in the vasa recta / peritubular capillaries, caused by efferent arteriole capillaries.
10. because higher pressure is necessary for filtration (hence the higher afferent arteriole pressure) and lower pressure is necessary in the capillaries for reabsorption.
11. the filtration fraction is generally 20% and is derived from the glomerular filtration rate / renal plasma flow.
12. capillary hydrostatic pressure is low, and oncotic pressure is high.
13. when the efferent arteriole constricts, the hydrostatic pressure in the capillaries drop and the oncotic pressure (because the filtration fraction increases, leaving more solute in the capillaries) increases. both of these conditions increase reabsorption.
14. a mechanism that ensures that 2/3 of the filtrate is reabsorbed in the proximal tubule despite changes in the GFR.
15. neuroendocrine control of reabsorption in the proximal and distal tubules.
16. angiotensin II, aldosterone, ADH, sympathetic nervous system.
17. in response to blood pressure drop (sensed by baroreceptors in afferent arteriole), or decreased solute concentration sensed by macula densa, renin is released by JGA cells.
18. in the liver and kidney, renin cleaves angiotensin I from angiotensinogen. angiotensin I is converted to angiotnesin II by angiotensin coverting enzyme (ACE) mostly in lungs, but also in heart and kidney.
19. releases aldosterone and promotes reabsorption of Na and water.
20. angiotensin II has a direct, fast effect on the proximal tubules: it constricts the afferent arteriole, the efferent arteriole, and stimulates the proximal tubule to reabsorb more Na+ and water.
21. angiotensin II has a slower more indirect effect on the distal tubules: it stimulates release of aldosterone from adrenal cortex, which increases Na+ and water reabsorption in distal tubules. it also stimulates the hypothalamus to secrete ADH as well as to provoke the thirst response, leading to fluid intake and increased blood pressure.
22. it is an angiotensin converting enzyme-inhibitor, which prevents ADH and aldosterone release, causing less reabsorption and thus lowering fluid volume and blood pressure.
23. increases Na+ reabsorption and K+ secretion. upregulates Na/K pump and Na channels in tubular membrane cells.
24. mineralocorticoid secreted by the adrenal cortex.
25. angiotensin II, high K+ levels in blood, ACTH released from anterior pituitary gland during stress response
26. emotional signals or drops in blood pressure.
27. aortic and carotid baroreceptors stimulate hypothalamus, which triggers sympathetic activity from medulla and spinal cord, activating the pre ganglionic neurons which innervate the prevertebral ganglia, and the post ganglionic neurons which innervate the tubular and arteriolar cells.
28. sympathetic activity stimulates constriction of afferent and efferent arterioles and stimulates renin release, thereby increasing reabsorption (see question 20)
29. sympathetic stimulation produces a response within seconds whereas the response of neuroendocrine stimulation occurs on the order of minutes.
30. baroreceptors can also stimulate ADH release in response to low blood pressure, which stimulates reabsorption in the collecting ducts and increases fluid volume and blood pressure.
31. atrial natriuretic peptide and pressure natriuresis.
32. released from granules in atrial baroreceptor cells.
33. increase GFR by dilating the afferent arteriole. decreases secretion of renin, ADH, and angiotensin II, inhibiting reabsorption of Na+ and water.
34. pressure natriuresis is the compensatory process in which increased blood pressure stimulates increased excretion of solute and water, thereby lowering blood pressure.
35. sodium channels and sodium / potassium pumps are downregulated and removed endocytically in proximal tubule cells, thereby decreasing reabsorption / increasing excretion.
36. nitric oxide is relased from the endothelium of the vasa recta in response to elevated blood pressures; this causes the hydrostatic pressure of the capillaries to go up and the oncotic pressure to go down, decreasing reabsorption and increasing excretion.
37. it is the point on the curve of salt excretion vs. blood pressure where the salt excretion (y axis) equals salt intake -- any deviation from this point will be eventually brought back by the homeostatic mechanisms discussed.
38. nitric oxide and angiotensin II.
GFR and RPF are thus maintained homeostatically by several different mechanisms against sharp increases or decreases in blood fluid volume and pressure. tubuloglomerular feedback is one such mechanism in which the afferent arteriole is stimulated to constrict in response to elevated blood pressure via a pathway that involves the macula densa sensing more solute particles-- causing the GFR and RPF to decrease back to normal levels. "myogenic" regulation is another, more reflexive feedback mechanism in which blood pressure changes stimulate baroreceptors in the afferent arteriole, which then constricts or dilates, depending if the blood pressure rises or falls, respectively.
we then look at the regulation of reabsorption, which occurs through multiple mechanisms. the first one mentioned is that of starling forces: the balance between hydrostatic and oncotic pressure in the capillaries. the efferent arteriole constricts and causes a pressure gradient such that while the pressure in the afferent arteriole and glomerulus is 60mmHg, the pressure in the efferent arteriole and the capillaries is 20mmHg. this pressure drop aids reabsorption in two ways: it lowers the hydrostatic pressure (less fluid coming into the capillaries), and raises the oncotic pressure (the pressure drop causes more fluid to be filtered, leaving more solutes in the plasma in the capillaries). both of these changes support reabsorption of solutes.
the next few mechanisms are all different molecules / hormones that counter blood pressure drops / increase reabsorption via different mechanisms. angiotensin II is one such molecule, and is created in response to renin release: renin cleaves angiotensin I from angiotensinogen in the kidney and liver, which is then converted to angiotensin II via angiotensin converting enzyme (ACE) in the lungs. angiotensin II has several effects on the kidney which all increase reabsorption. first, it works directly and quickly on the proximal tubules, constricting both the afferent and efferent arterioles.
second, it stimulates the release of aldosterone from the adrenal cortex, which increases the reabsorption in the distal tubules. it does so by upregulating the amount of Na/K pumps and sodium channels in the tubular membrane, thereby facilitating sodium (and thus water, which osmotically follows) reabsorption. aldosterone is also secreted in response to high potassium levels, since upregulating the Na/K pumps would increase potassium excretion.
third, it stimulates the release of ADH from the hypothalamus, which increases the collecting duct's permeability to water and thus aids reabsorption. ADH can also be released in response to blood pressure drops via the sympathetic nervous system, but generally only in response to large fluid drops such as in the case of hemorrage. (ADH is described in greater detail in lecture 3). finally, angiotensin II elicits the thirst impulse in the hypothalamus, causing an increase of fluid volume.
the next mechanism for increasing reabsorption is via the sympathetic nervous system. this pathway starts at the baroreceptors in the aortic and carotid arch, which can sense a drop in blood volume/pressure, stimulating the hypothalamus, which then triggers sympathetic activity from the medulla and spinal cord, which ultimately stimulate constriction of the afferent and efferent arteriole (recall that this increases reabsorption as in the case of angiotensin II above). this pathway can also be triggered by emotional cues such as fright and can produce a response within seconds, whereas the renin/angiotensin response is more on the order of minutes.
we then look at the factors that have the opposite effect: increasing excretion and decreasing reabsorption, generally in response to an increase in fluid volume (ingesting large amounts of liquid), increased Na+ concentration (which causes increased retention of fluid) or increased blood pressure. the first mechanism is via the atrial natriuretic peptide, which is released from the granules of the atrial baroreceptor cells in response to elevated blood pressure. in the kidney, ANP dilates the afferent arteriole, increasing GFR, and also inhibits the release of the molecules mentioned above: angiotensin II, ADH, and aldosterone. "pressure natriuresis" is the other mechanism by which excretion can be increased, and is the process in which increased blood pressure causes increased excretion of solute and water. this is accomplished via two mechanisms: first, the sodium channels and Na/K pumps are downregulated and endocytos-ed in the proximal tubule, decreasing its ability to reabsorb. second, nitric oxide is released from the endothelium of the vasa recta, which causes it to vasodilate- this increases the hydrostatic pressure and decreases the oncotic pressure, which via starling forces decreases the capillaries' absorptive capacity.
questions
1. volume of blood and extracellular fluid is regulated by...
2. sodium reabsorption is regulated by...
3. describe what happens when the GFR deviates too low or high from the homeostatic condition.
4. what regulates RBF (renal blood flow) and GFR?
5. what is the usual problem regarding regulation of renal filtration?
6. describe the tubuloglomerular feedback mechanism when body fluid volume is increased.
7. what does the macula densa release that constricts the afferent arteriole?
8. describe the myogenic mechanism for regulating renal blood flow.
9. what is the pressure drop between the afferent arterioles and the vasa recta and what is it caused by?
10. why is the pressure drop necessary?
11. what is the filtration fraction and how is it derived?
12. what are the two conditions in the capillaries necessary for reabsorption?
13. describe how the efferent arteriole influences reabsorption.
14. what is glomerulotubular balance?
15. where is fine regulation of Na+ levels and extracellular volume is carried out by?
16. what are the neuroendocrine factors that increase reabsorption and decrease excretion?
17. where and in response to what is renin released in the nephron?
18. describe the production of angiotensin II.
19. what does angiotensin II do in the kidneys?
20. describe the actions of angiotensin II on the proximal tubules of the nephron.
21. describe the actions of angiotensin II on the distal tubules of the nephron.
22. how does Captopril work?
23. describe the effect of aldosterone on the the distal tubules.
24. aldosterone is a ... secreted by the ...
25. aldosterone is released in response to...
26. sympathetic reflexes are triggered by...
27. describe how baroreceptor stimulation can lead to sympathetic stimulation of arteriole and tubular cells.
28. describe how sympathetic activity facilitates reabsorption.
29. describe the response time of sympathetic stimulation vs. that of the neuroendocrine stimulation.
30. describe ADH's role in blood volume/pressure regulation.
31. what are the two factors that decrease reabsorption / increase excretion?
32. where is atrial natruretic peptide released from?
33. how does ANP increase excretion?
34. what is pressure natriuresis?
35. what is the mechanism that it uses?
36. what role does nitric oxide play in pressure natriuresis?
37. what is the pressure natriuresis equilibrium point?
38. what are the two factors that counterbalance each other in the vasoconstriction / vasodilation of the vasa recta?
answers
1. the amount of sodium that is excreted
2. neuroendocrine factors.
3. when GFR is too low, unwanted waste products might be reabsorbed. if GRF is too high, nutrients might be excreted.
4. changes in the resistance of the afferent arteriole.
5. renal failure, where a drop of blood pressure causes too significant a drop in the renal filtration rate.
6. increased body fluid volume increases GFR and RBF, which increases solute concentration in the tubule. macula densa senses increased solute concentration and stimulates afferent arteriole to constrict, which decreases GFR and RBF to normal levels.
7. adenosine.
8. the afferent arterioles have barorecptors that are stretched when blood pressure rises, causing them to constrict reflexively, thus lowering the RBF to a normal rate.
9. 60mmHg in the afferent arterioles and 20mmHg in the vasa recta / peritubular capillaries, caused by efferent arteriole capillaries.
10. because higher pressure is necessary for filtration (hence the higher afferent arteriole pressure) and lower pressure is necessary in the capillaries for reabsorption.
11. the filtration fraction is generally 20% and is derived from the glomerular filtration rate / renal plasma flow.
12. capillary hydrostatic pressure is low, and oncotic pressure is high.
13. when the efferent arteriole constricts, the hydrostatic pressure in the capillaries drop and the oncotic pressure (because the filtration fraction increases, leaving more solute in the capillaries) increases. both of these conditions increase reabsorption.
14. a mechanism that ensures that 2/3 of the filtrate is reabsorbed in the proximal tubule despite changes in the GFR.
15. neuroendocrine control of reabsorption in the proximal and distal tubules.
16. angiotensin II, aldosterone, ADH, sympathetic nervous system.
17. in response to blood pressure drop (sensed by baroreceptors in afferent arteriole), or decreased solute concentration sensed by macula densa, renin is released by JGA cells.
18. in the liver and kidney, renin cleaves angiotensin I from angiotensinogen. angiotensin I is converted to angiotnesin II by angiotensin coverting enzyme (ACE) mostly in lungs, but also in heart and kidney.
19. releases aldosterone and promotes reabsorption of Na and water.
20. angiotensin II has a direct, fast effect on the proximal tubules: it constricts the afferent arteriole, the efferent arteriole, and stimulates the proximal tubule to reabsorb more Na+ and water.
21. angiotensin II has a slower more indirect effect on the distal tubules: it stimulates release of aldosterone from adrenal cortex, which increases Na+ and water reabsorption in distal tubules. it also stimulates the hypothalamus to secrete ADH as well as to provoke the thirst response, leading to fluid intake and increased blood pressure.
22. it is an angiotensin converting enzyme-inhibitor, which prevents ADH and aldosterone release, causing less reabsorption and thus lowering fluid volume and blood pressure.
23. increases Na+ reabsorption and K+ secretion. upregulates Na/K pump and Na channels in tubular membrane cells.
24. mineralocorticoid secreted by the adrenal cortex.
25. angiotensin II, high K+ levels in blood, ACTH released from anterior pituitary gland during stress response
26. emotional signals or drops in blood pressure.
27. aortic and carotid baroreceptors stimulate hypothalamus, which triggers sympathetic activity from medulla and spinal cord, activating the pre ganglionic neurons which innervate the prevertebral ganglia, and the post ganglionic neurons which innervate the tubular and arteriolar cells.
28. sympathetic activity stimulates constriction of afferent and efferent arterioles and stimulates renin release, thereby increasing reabsorption (see question 20)
29. sympathetic stimulation produces a response within seconds whereas the response of neuroendocrine stimulation occurs on the order of minutes.
30. baroreceptors can also stimulate ADH release in response to low blood pressure, which stimulates reabsorption in the collecting ducts and increases fluid volume and blood pressure.
31. atrial natriuretic peptide and pressure natriuresis.
32. released from granules in atrial baroreceptor cells.
33. increase GFR by dilating the afferent arteriole. decreases secretion of renin, ADH, and angiotensin II, inhibiting reabsorption of Na+ and water.
34. pressure natriuresis is the compensatory process in which increased blood pressure stimulates increased excretion of solute and water, thereby lowering blood pressure.
35. sodium channels and sodium / potassium pumps are downregulated and removed endocytically in proximal tubule cells, thereby decreasing reabsorption / increasing excretion.
36. nitric oxide is relased from the endothelium of the vasa recta in response to elevated blood pressures; this causes the hydrostatic pressure of the capillaries to go up and the oncotic pressure to go down, decreasing reabsorption and increasing excretion.
37. it is the point on the curve of salt excretion vs. blood pressure where the salt excretion (y axis) equals salt intake -- any deviation from this point will be eventually brought back by the homeostatic mechanisms discussed.
38. nitric oxide and angiotensin II.
Wednesday, January 14, 2009
organ systems: renal system part 3- osmoregulation and ADH
this lecture is the third in the series on the kidney and talks about one of its main functions, osmoregulation, which is the kidney's control over the concentration of solute and volume of body fluid by controlling the permeability of different sections of the nephron. the first section introduces some basic concepts regarding osmolarity in general- osmolarity is defined as moles of solute per kg of solvent and is functionally equivalent to osmolality (moles/L). the tonicity of a fluid refers to the osmolality and thus the amount of dissolved solute. if a cell is in a hypertonic solution, that means the solution it is in has more solute dissolved in it, and thus it has the tendency to shrink because of the water will flow into solution. if a cell is in a hypotonic solution, the cell now has a higher concentration of dissolved solute particles, causing water to flow inward, causing the cell to swell. thus in order to avoid such potentially damaging forces to the cell, osmolarity of body fluids need to be tightly regulated.
we then talk about the mechanism of osmoregulation in the kidney, beginning by looking at the hypertonic medullary interstitium. this is the space outside of the nephritic tubules that has a high concentration of solutes such as NaCl and urea, which are suspended in hyaluronic acid gel and albumin. the high concentration of solute (thus "hypertonic") in the interstitium provides an osmotic force for water to be reabsorbed from the nephron back into the body fluids. urea is looked at first: urea is in general a byproduct of protein metabolism- breaking down proteins forms nitrogen, which is converted to the non toxic, water soluble ammonia. ammonia is reduced in the muscles and peripheral tissues to glutamine, and in the liver glutamine is converted to urea. in the kidney, urea is filtered into the nephron and 50% is reabsorbed in the proximal tubule, while 10% is transported out into the lower medullary interstitium, contributing to its hypertonicity, and 40% is excreted in the urine.
NaCl is reabsorbed into the interstitium in the thin and thick ascending loops of henle. NaCl is first concentrated in the descending loop of henle-- this is due to osmotic pressure from high lactate concentrations (which is produced by the vasa recta because of its use of anaerobic respiration) in the surrounding interstitium, pulling water out from the descending loop. the descending loop is permeable to water but not to sodium, which allows the NaCl to become progressively more concentrated. the concentrated NaCl then flows passively out of the thin ascending loop down its concentration gradient into the interstitium, and it is actively pumped out in the thick ascending loop.
thus, the high concentrations of solute cause the interstitium to have a higher solute concentration than the nephritic tubules and reabsorption is facilitated. the vasa recta's role is then touched upon-- specifically, why it does not dilute the hypertonicity of the interstitium, since it is permeable to both water and sodium. as the blood flows down the vasa recta into the deeper medulla, solute is absorbed from the hypertonic interstitium. however, because of the vasa recta's parallel/hairpin shape, on the way up, solute diffuses back into the interstitium, so that the net effect is simply that solute is removed from the lower medullary interstitium and moved to the upper medullary interstitium.
the role of ADH is looked at in some detail. ADH "anti diuretic hormone" is a hormone that increases the permeability of the collecting duct by upregulating the transcription of aquaporin proteins, which then migrate to the cell surface and allow water to pass through the tubule (recall transcellular transport from lecture 1 on the kidney). it is produced in the PV and SO nuclei in the hypothalamus, transported into the pituitary via axonal transport, and released into the bloodstream. ADH can be produced in response to high sodium levels in the body, causing more water to be reabsorbed and the sodium levels to be diluted. ADH production can also be decreased in response to an excess of water- reducing the permeability of the collecting ducts and causing more water to be excreted in the urine. finally, the baroreceptors that sense mean arterial pressure of the blood inhibit ADH production if blood pressure is too high, reducing blood fluid volume and thus lowering blood pressure.
questions
1. what are the two parameters that regulate extracellular fluid size and composition?
2. excretion of water volume is regulated by indicators of...
3. excretion of sodium is regulated by signals derived from...
4. what are the units of osmolality?
5. a cell in a hypotonic solution...
6. a cell in a hypertonic solution...
7. what are the two factors that influence water reabsorption in the collecting ducts of the kidney?
8. what makes the medullay interstitium hypertonic?
9. urea enters the interstitium from...
10. NaCl enters the interstitium from...
11. what makes up the gel that suspends the solutes in the interstitium?
12. where does urea enter the tubules in short nephrons?
13. how does urea get recirculated back into the tubules?
14. 50% of urea is reabsorbed...
15. the bulk of the deep interstitium's hypertonicity is from...
16. which part of the nephron is impermeable to water?
17. what happens to urea in the collecting ducts?
18. urea is transported into the interstitium via...
19. urea is a byproduct of...
20. amino acid nitrogen forms...
21. describe the formation of urea from ammonium.
22. how does NaCl accumulate in the interstitium of the outer medulla?
23. how does NaCl accumulate in the interstitium of the inner medulla?
24. describe lactate's role in NaCl accumulation in the interstitium.
25. descending loop is permeable to...
26. ascending loop is permeable to...
27. describe the absorbption of solutes in the vasa recta.
28. how does the vasa recta preserve the hypertonicity of the interstitium?
29. where is ADH released from?
30. what does ADH do in the nephron?
31. describe the effect of water reabsorption on the blood.
32. how does ADH increase water permeability of the collecting ducts?
33. what is the minor calyx's role in water reabsorption?
34. action of minor calyces first seen in...
35. how often do rat pelvo-calyceal walls contract?
36. what happens during pulsatile contractions in the rat pevlo-calyceal walls?
37. what happens during relaxation?
38. what are the major locations within the hypothalamus that relate to release of ADH?
39. describe the production of ADH.
40. what do osmoreceptor cells in the hypothalamus do?
41. describe the effects of increased and decreased plasma Na+ concentration on the release of ADH.
42. how are baroreceptors in the heart related to ADH?
43. what are some other factors that stimulate/inhibit ADH release?
44. what is central / pituitary DI?
45. what is nephrogenic DI?
46. effects of lowered ADH include...
47. what is SIADH?
48. what does the hypothalamic thirst center respond to?
49. excess water consumption...
50. polydipsia is...
answers
1. fluid volume and solute concentration (sodium and water)
2. sodium concentration
3. hydrostatic pressure / body fluid volume
4. mol solute / kg solvent
5. swells
6. shrinks
7. hypertonic medullary interstitium provides osmotic pressure for water to travel outward. ADH controls permeability of tubular epithelium.
8. urea and NaCl
9. collecting duct
10. thin and thick portions of the ascending loop.
11. hyaluronic acid and albumin.
12. from the descending vasa recta
13. either through the ascending vasa recta or directly back into the tubules from the interstitium.
14. in the proximal convoluted tubule
15. the 10% of the urea that is reabsorbed in the collecting ducts.
16. the thick ascending loop of henle, the collecting tubules, and the upper collecting ducts.
17. it gets concentrated via reabsorbption of water.
18. ADH dependent transporters in the deepest part of the collecting ducts.
19. protein digestion
20. nitrogen, which is then converted into ammonia, which can be dissolved and excreted.
21. muscles and peripheral tissues convert ammonia into glutamine from reduction of alpha keto glutarate. glutamine is converted in the liver back into urea.
22. active transport via sodium/potassium pumps.
23. passive transport from thin ascending loop.
24. lactate is produced from the anaerobic respiration that occurs in the vasa recta ("due to low blood perfusion"), and accumulates in the interstitium. this pulls water out of the descending loop of henle, thereby concentrating the NaCl. the NaCl is then passively diffused out from the thing ascending loop or actively transported in the thick ascending loop.
25. water
26. sodium
27. absorbs solutes in the inner medulla but releases them in the outer medulla.
28. although blood absorbs solutes from and loses water to the interstitium as it travels down the descending vasa recta, the flows are reversed in the ascending vasa recta-- a consequence of the hairpin structure.
29. hypothalamus into the bloodstream.
30. increases permeability of collecting duct to water, allowing for reabsorption
31. increases blood volume and decreases osmolarity.
32. by increasing the transcription and translation of the genes that code for aquaporins, which are then translocated from the cytoplasm to the cell membrane.
33. it puts physical pressure on the collecting ducts and interstitium, facilitating water reabsorption.
34. the rat unipapillate model.
35. 15-40 times a minutes
36. during contraction, water is squeezed out of the collecting ducts into the interstitium (held by hyaluronic acid), concentrating the urine.
37. during relaxation, decreased interstitial pressure draws water from the interstitium into the vasa recta.
38. supraoptic and paraventricular hypothalamic nuclei.
39. ADH is synthesized in the SO and PV nuclei in the hypothalamus, transported via axons into the posterior pituitary, and then released into circulation.
40. stimulate release of ADH from PV and SO nuclei.
41. increased Na+ (from food intake) stimulates release of ADH, which causes reabsorption of water, diluting the Na+. decreased Na+ (from water intake) decreases ADH release; water is excreted in urine.
42. baroreceptors are the stretch receptors that monitor blood flow. if blood pressure gets too high, they can inhibit ADH production, which will cause net fluid loss and decrease blood pressure.
43. nausea, nicotine, morphine stimulate ADH release. alcohol inhibits ADH release.
44. reduced pituitary secretion of ADH due to genetics, head trauma, brain tumor, or infections.
45. nephrogenic DI is tubular resistance to ADH due to errors in ADH receptors or aquaporins.
46. lowered permeability of collecting ducts reduces water reabsorption, reduces urea reabsorption (and therefore lowers hypertonicity of interstitium), leads to copious urine excretion.
47. unregulated release of ADH causes excess reabsorption of water, concentrated urine, and decreased Na+ blood concentration.
48. ECF osmolarity, drop in blood volume, angiotensin II, dryness of mouth/throat
49. suppresses ADH release
50. water intoxication- causes headache, loss of apptite, lethargy, nausea. decrease in plasma sodium concentration.
we then talk about the mechanism of osmoregulation in the kidney, beginning by looking at the hypertonic medullary interstitium. this is the space outside of the nephritic tubules that has a high concentration of solutes such as NaCl and urea, which are suspended in hyaluronic acid gel and albumin. the high concentration of solute (thus "hypertonic") in the interstitium provides an osmotic force for water to be reabsorbed from the nephron back into the body fluids. urea is looked at first: urea is in general a byproduct of protein metabolism- breaking down proteins forms nitrogen, which is converted to the non toxic, water soluble ammonia. ammonia is reduced in the muscles and peripheral tissues to glutamine, and in the liver glutamine is converted to urea. in the kidney, urea is filtered into the nephron and 50% is reabsorbed in the proximal tubule, while 10% is transported out into the lower medullary interstitium, contributing to its hypertonicity, and 40% is excreted in the urine.
NaCl is reabsorbed into the interstitium in the thin and thick ascending loops of henle. NaCl is first concentrated in the descending loop of henle-- this is due to osmotic pressure from high lactate concentrations (which is produced by the vasa recta because of its use of anaerobic respiration) in the surrounding interstitium, pulling water out from the descending loop. the descending loop is permeable to water but not to sodium, which allows the NaCl to become progressively more concentrated. the concentrated NaCl then flows passively out of the thin ascending loop down its concentration gradient into the interstitium, and it is actively pumped out in the thick ascending loop.
thus, the high concentrations of solute cause the interstitium to have a higher solute concentration than the nephritic tubules and reabsorption is facilitated. the vasa recta's role is then touched upon-- specifically, why it does not dilute the hypertonicity of the interstitium, since it is permeable to both water and sodium. as the blood flows down the vasa recta into the deeper medulla, solute is absorbed from the hypertonic interstitium. however, because of the vasa recta's parallel/hairpin shape, on the way up, solute diffuses back into the interstitium, so that the net effect is simply that solute is removed from the lower medullary interstitium and moved to the upper medullary interstitium.
the role of ADH is looked at in some detail. ADH "anti diuretic hormone" is a hormone that increases the permeability of the collecting duct by upregulating the transcription of aquaporin proteins, which then migrate to the cell surface and allow water to pass through the tubule (recall transcellular transport from lecture 1 on the kidney). it is produced in the PV and SO nuclei in the hypothalamus, transported into the pituitary via axonal transport, and released into the bloodstream. ADH can be produced in response to high sodium levels in the body, causing more water to be reabsorbed and the sodium levels to be diluted. ADH production can also be decreased in response to an excess of water- reducing the permeability of the collecting ducts and causing more water to be excreted in the urine. finally, the baroreceptors that sense mean arterial pressure of the blood inhibit ADH production if blood pressure is too high, reducing blood fluid volume and thus lowering blood pressure.
questions
1. what are the two parameters that regulate extracellular fluid size and composition?
2. excretion of water volume is regulated by indicators of...
3. excretion of sodium is regulated by signals derived from...
4. what are the units of osmolality?
5. a cell in a hypotonic solution...
6. a cell in a hypertonic solution...
7. what are the two factors that influence water reabsorption in the collecting ducts of the kidney?
8. what makes the medullay interstitium hypertonic?
9. urea enters the interstitium from...
10. NaCl enters the interstitium from...
11. what makes up the gel that suspends the solutes in the interstitium?
12. where does urea enter the tubules in short nephrons?
13. how does urea get recirculated back into the tubules?
14. 50% of urea is reabsorbed...
15. the bulk of the deep interstitium's hypertonicity is from...
16. which part of the nephron is impermeable to water?
17. what happens to urea in the collecting ducts?
18. urea is transported into the interstitium via...
19. urea is a byproduct of...
20. amino acid nitrogen forms...
21. describe the formation of urea from ammonium.
22. how does NaCl accumulate in the interstitium of the outer medulla?
23. how does NaCl accumulate in the interstitium of the inner medulla?
24. describe lactate's role in NaCl accumulation in the interstitium.
25. descending loop is permeable to...
26. ascending loop is permeable to...
27. describe the absorbption of solutes in the vasa recta.
28. how does the vasa recta preserve the hypertonicity of the interstitium?
29. where is ADH released from?
30. what does ADH do in the nephron?
31. describe the effect of water reabsorption on the blood.
32. how does ADH increase water permeability of the collecting ducts?
33. what is the minor calyx's role in water reabsorption?
34. action of minor calyces first seen in...
35. how often do rat pelvo-calyceal walls contract?
36. what happens during pulsatile contractions in the rat pevlo-calyceal walls?
37. what happens during relaxation?
38. what are the major locations within the hypothalamus that relate to release of ADH?
39. describe the production of ADH.
40. what do osmoreceptor cells in the hypothalamus do?
41. describe the effects of increased and decreased plasma Na+ concentration on the release of ADH.
42. how are baroreceptors in the heart related to ADH?
43. what are some other factors that stimulate/inhibit ADH release?
44. what is central / pituitary DI?
45. what is nephrogenic DI?
46. effects of lowered ADH include...
47. what is SIADH?
48. what does the hypothalamic thirst center respond to?
49. excess water consumption...
50. polydipsia is...
answers
1. fluid volume and solute concentration (sodium and water)
2. sodium concentration
3. hydrostatic pressure / body fluid volume
4. mol solute / kg solvent
5. swells
6. shrinks
7. hypertonic medullary interstitium provides osmotic pressure for water to travel outward. ADH controls permeability of tubular epithelium.
8. urea and NaCl
9. collecting duct
10. thin and thick portions of the ascending loop.
11. hyaluronic acid and albumin.
12. from the descending vasa recta
13. either through the ascending vasa recta or directly back into the tubules from the interstitium.
14. in the proximal convoluted tubule
15. the 10% of the urea that is reabsorbed in the collecting ducts.
16. the thick ascending loop of henle, the collecting tubules, and the upper collecting ducts.
17. it gets concentrated via reabsorbption of water.
18. ADH dependent transporters in the deepest part of the collecting ducts.
19. protein digestion
20. nitrogen, which is then converted into ammonia, which can be dissolved and excreted.
21. muscles and peripheral tissues convert ammonia into glutamine from reduction of alpha keto glutarate. glutamine is converted in the liver back into urea.
22. active transport via sodium/potassium pumps.
23. passive transport from thin ascending loop.
24. lactate is produced from the anaerobic respiration that occurs in the vasa recta ("due to low blood perfusion"), and accumulates in the interstitium. this pulls water out of the descending loop of henle, thereby concentrating the NaCl. the NaCl is then passively diffused out from the thing ascending loop or actively transported in the thick ascending loop.
25. water
26. sodium
27. absorbs solutes in the inner medulla but releases them in the outer medulla.
28. although blood absorbs solutes from and loses water to the interstitium as it travels down the descending vasa recta, the flows are reversed in the ascending vasa recta-- a consequence of the hairpin structure.
29. hypothalamus into the bloodstream.
30. increases permeability of collecting duct to water, allowing for reabsorption
31. increases blood volume and decreases osmolarity.
32. by increasing the transcription and translation of the genes that code for aquaporins, which are then translocated from the cytoplasm to the cell membrane.
33. it puts physical pressure on the collecting ducts and interstitium, facilitating water reabsorption.
34. the rat unipapillate model.
35. 15-40 times a minutes
36. during contraction, water is squeezed out of the collecting ducts into the interstitium (held by hyaluronic acid), concentrating the urine.
37. during relaxation, decreased interstitial pressure draws water from the interstitium into the vasa recta.
38. supraoptic and paraventricular hypothalamic nuclei.
39. ADH is synthesized in the SO and PV nuclei in the hypothalamus, transported via axons into the posterior pituitary, and then released into circulation.
40. stimulate release of ADH from PV and SO nuclei.
41. increased Na+ (from food intake) stimulates release of ADH, which causes reabsorption of water, diluting the Na+. decreased Na+ (from water intake) decreases ADH release; water is excreted in urine.
42. baroreceptors are the stretch receptors that monitor blood flow. if blood pressure gets too high, they can inhibit ADH production, which will cause net fluid loss and decrease blood pressure.
43. nausea, nicotine, morphine stimulate ADH release. alcohol inhibits ADH release.
44. reduced pituitary secretion of ADH due to genetics, head trauma, brain tumor, or infections.
45. nephrogenic DI is tubular resistance to ADH due to errors in ADH receptors or aquaporins.
46. lowered permeability of collecting ducts reduces water reabsorption, reduces urea reabsorption (and therefore lowers hypertonicity of interstitium), leads to copious urine excretion.
47. unregulated release of ADH causes excess reabsorption of water, concentrated urine, and decreased Na+ blood concentration.
48. ECF osmolarity, drop in blood volume, angiotensin II, dryness of mouth/throat
49. suppresses ADH release
50. water intoxication- causes headache, loss of apptite, lethargy, nausea. decrease in plasma sodium concentration.
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