B. SYNDROME: Chronic Renal Failure

Question 1

(Chronic Renal Failure (CRF))

1. aka what?

(examples of processes that may lead to this)

a. Chronic glomerulonephritis
b. Chronic pyelonephritis
c. Chronic interstitial nephritis
d. Polycystic kidney disease
e. Neoplasia (most often metastatic neoplasms)
f. Amyloidosis

Answer 1

1. Chronic Kidney Disease (CKD)

Question 2

(1)

(Chronic Renal Failure)

(Pathogenesis)

1. as nephrons lost to disease, smaller amount of nephrons have to do more glomerular filtration - what happens due to this?
2. At what point can nephrons not longer compensate?
3. what happens at this point?
4. in cats and dogs, loss of 2/3 associated with what?
5. loss of 3/4 or more results in what?

–> around this time polyuria also develops –>

Answer 2

1. compensation - each nephron handles more –> hypertrophy
2. when 1/3 of nephrons left
3. glomerular filtration rate (GFR) decreases –> rise in blood urea nitrogen (BUN) and serum creatinine conc (called azotemia)

(BUN and creatinine give approx estimate of total renal GFR)

4. loss of urine conc ability (isosthenuria)
5. azotemia

Question 3

(2)

(Chronic Renal Failure)

(Pathogenesis)

1-2. Polyuria (lots of urine) Develops due to what two factors?

3. When only 1/4 of nephrons remain - what develops?

Answer 3

1. not enough nephrons to maintain medullary solute gradient and countercurrent exchange (renal tubules play important role in this)
2. fewer nephrons means worse filtration - solutes stay in ultrafiltrate - retain water
3. uremia

Question 4

(3)

(Chronic Renal Failure)

(Uremia)

1. uremia is hallmark of what?
2. comprised of findings such as azotemia, polyuria, polydipsia, metabolic acidosis, electrolyte abnormalities (eg: hyperphosphatemia), metastatic mineralization, oral and gastrointestinal ulcers, and non-regenerative anemia.

Answer 4

1. advanced chronic renal failure

Question 5

(4)

(Chronic Renal Failure)

(Uremia)

(Fluid, Electrolyte, and Acid-Base Disturbances)

1. Why does dehydration occur?

can polydipsia solve problem?

what can make dehyrdation worse?

Answer 5

1. can’t concentrate urine

generally no

vomiting & diarrhea (seen in CRF patients)

Question 6

(5)

(Chronic Renal Failure)

(Uremia)

(Fluid, Electrolyte, and Acid-Base Disturbances)

(Salt and Water Retention)

1. volume depletion due to dehydration causes increased secretion of what from JG apparatus in kidney?

which does what?

what does angiotension II do?

what does aldosterone do?

2. At one point does the above mechanism overcome polyuria?

Answer 6

1. renin

converts angiotensinogen –> angiotensin I (which then quickly forms angiotensin II)

causes arteriolar vasoconstriction –> hypertension, stimulates aldosterone secretion from adrenal cortex

increased Na (thus H2O) retention (thus causing hypertension seen in CRF)

2. terminal (oliguric) phase of CRF when severe reduction in total GFR may lead to overhydration

Question 7

(6)

(Chronic Renal Failure)

(Uremia)

(Fluid, Electrolyte, and Acid-Base Disturbances)

(Metabolic Acidosis)

1. occurs due to what?
2. What causes decrease in NH3?
3. There is also reduction in production/reuptake of what?

reduced net excretion of what?

Answer 7

1. reduced renal ammonia production/decreased bicarbonate uptake

(renal tubular epithelial cells make NH3 that goes into tubular lumen –> combines with H to make NH4 –> cannot reenter epi cell –> excreted in urine)

2. less tubules making it due to loss of functional tubules - even though each tubule is making more
3. bicarbonate

phosphate

Question 8

(8)

(Chronic Renal Failure)

(Uremia)

(Abnormalities in Calcium, Phosphate, and Bone Metabolism)

1. When GFR 25% of normal, phosphate excretion is insufficient and serum conc rise
2. elevated serum phosphate causes what?
3. Hypocalcemia triggers what?

In CRF, what else leads to high PTH levels?

4. high PTH causes what?
5. renal damage and high PO4 reduce production of what?

which leads to what?

6. abnormal Ca and P also result in what?

Answer 8

2. increases Ca uptake into tissues (causing transient hypocalcemia)
3. increased PTH –> parathyroid hyperplasia (2o renal hyperparathyroidism)

reduced clearance

4. demineralization of bone and medullary/myelo- fibrosis (called renal osteodystrophy or “rubber jaw”)

predisposes to fractures

5. 1,25-dihydroxy-vitamin D

reduced Ca GI absorption (hypocalcemia)

6. metastatic minearliaztion of lung, vessels, GI (gastric mucosa)

Question 9

(8)

(Chronic Renal Failure)

(Uremia)

(Hematopoietic Manifestations)

1. characterized by normocytic. normochromic anemia (non-regenerative) due to what mainly?
2. also due to what?

(GI Manifestations)

3. what are often present?

Answer 9

1. decreased renal production of erythropoetin (controls RBC production)
2. anemia of chronic disease and uremic toxins fucking up erythrocytes
3. oral ulcers (tongue; uremic glossitis) and erosive gastritis (“uremic gastritis)

Question 10

(9)

(Chronic Renal Failure)

(Mech of Progression of Renal Injury)

(Background)

1. Once GFR reduced to 30-50% will resolution of primary disease prevent progression to end-stage renal failure?
2. why is this?

Answer 10

1. no
2. remaining nephrons undergo changes to make up for lost ones (glomerular and tubular hypertrophy/hyperplasia and hemodynamic changes)

these changes lead to sclerosis(hardening of tissue)/loss of fuction

Question 11

(10)

(Chronic Renal Failure)

(Mech of Progression of Renal Injury)

(Glomerulosclerosis)

1. blood flow to remaining glomeruli increased how?

dilation of which is greater?

results in what?

2. glomerular hypertension leads to damage to what?

causing what?

3. increased macromolecules into mesangium and stretching of mesangial cells cause what?

what may cause this?

4. Can pharmacologic blockade of hypertension prevent glomerulosclerosis?

Answer 11

1. vasodilation of afferent/efferent arterioles

afferent

increased in glomerular BP (hypertension)

2. glomerulat epi and endo cells

increased permeability to proteins/macromolecules

3. increased production of matrix and mesangial cell proliferation

TGF-beta (and other inflammatory mediators)

4. yep

Question 12

(11)

(Chronic Renal Failure)

(Mech of Progression of Renal Injury)

(Glomerulosclerosis - cont)

1. In chronic disease (eg. glomerulonephritis) severly affected glomeruli shrink and become hyalinized - due to what?
2. The sclerotic or obscoelescent glomeruli are hypocellualar and non-functional.
3. What is the distribution of glomerularsclerosis like?

Answer 12

1. increase in fibrous CT, mesangial matrix

loss of glomerular capillaries

3. can but multifocal or affect all (generalized)

can involve entire glomerular tuft (global) or just portions (segmental)

Question 13

(12)

(Chronic Renal Failure)

(Mech of Progression of Renal Injury)

(Tubulointerstitial Damage)

1. in addition to glomerular damage - also get prominent interstital fibrosis along with tubular damage and loss

(this lesion correlates better with loss of function that glomerulosclerosis)

2-4. What three things cause?

Answer 13

2. ischemic (loss of tubular blood supply)
3. increased ammoniagenesis by renal tubules

activates complement –> release of inflammatory mediators from luekocytes

4. proteinuria (most important)

activate renal tubule epithelial cells –> release cytokines and grwoth factors –> interstital fibrosis

Question 14

(13)

(Chronic Renal Failure)

(Mech of Progression of Renal Injury)

(Morphological)

1. become initially enlarged, increased mesangial matrix, mesangial hypercellularity

focal adhesions between what?

eventually become what?

2. Do these glomeruli show immune deposits (by IF or EM) characteristic of immune-mediated GN?
3. What accompanies the loss of nephrons?
4. what two things have been shown to be beneficial in slowing sclerosis?

Answer 14

1. glomerulus and Bowman’s capsule

completely collapsed

2. no
3. cortical and medullary interstital fibrosis
4. reducted dietary protein and antihypertensive therapy