1. Kidney Function & Disease
NFSC 370
McCafferty

2. 1. Glomerulus – filtering unit
Structure
Nephron:
functional unit of the kidney. Each kidney has over a million nephrons.
Composed of:
1. Glomerulus – filtering unit
network of capillaries originating from the afferent arteriole
surrounded by Bowman’s capsule

3. 3. Tubule composed of distinct segments:
2. Bowman’s capsule:
functions as a filter in the formation of urine
3. Tubule composed of distinct segments:
proximal tubule, descending and ascending loop of Henle, distal tubule, and collecting tubule (and collecting duct).

4. peritubular capillaries Loop of Henle
Efferent Arteriole
Proximal Tubule
Afferent Arteriole
Distal Tubule
Glomerulus
Bowman’s Capsule
Collecting Duct
peritubular capillaries
Loop of Henle

5. Glomerular Filtration:
Glomerular filtrate: the fluid that filters through the glomerulus into Bowman’s Capsule, AKA glomerular capsule (pressure of blood in the glomerulus causes fluid to filter through the glomerular capillaries and into Bowman’s Capsule).
From there, blood flows into the proximal tubule  Loop of Henle  distal tubule  collecting tubule  collecting duct (which collects fluid from many nephrons)
Collecting duct empties into the renal pelvis  ureters  urinary bladder

6. As glomerular filtrate flows through the tubules, >99% of water and varying amounts of solutes are reabsorbed into the peritubular capillaries (capillaries that surround the tubule system).
Substances are also secreted from peritubular capillaries directly into the tubular fluid to be excreted.
The remaining water and solutes becomes urine.

7. Autoregulation of GFR: 2 Feedback Mechanisms
Autoregulation of GFR: 2 Feedback Mechanisms
GFR = Glomerular Filtration Rate:
The volume of blood plasma filtered out of the glomeruli of both kidneys per minute. Normal GFR = ml/min Best estimate of kidney function
(Note: GFR declines with age)

8. Age
Average GFR
20-29
116
30-39
107
40-49 99
50-59 93
60-69 85
70+ 75
From NHANES III: GFR declines by 1 ml/yr after age with some variation in “healthy” individuals
Kidney Disease Outcomes Quality Initiative
NKF, K/DOQI CKD, CKD Guidelines, 2002
Thanks to Joyce Ezaki-Yamaguchi, RD

9. If GFR drops, afferent arteriole dilates to increase glomerular blood flow and increase pressure, thereby increasing GFR

10. 2. If GFR drops, renin is released resulting in the conversion of angiotensin I to II. The efferent arteriole constricts, increasing glomerular pressure, and increasing GFR.

11. Functions of the Kidneys A. Homeostatic Functions
1. Waste excretion (urine formation)
a. Nitrogenous end products: urea, creatinine, uric acid, etc.
b. Metabolic degradation of peptide hormones: glucagon, insulin, PTH, growth hormone, FSH, and gastrin.
2. Fluid/electrolyte balance (Na+, K+, water)
3. Acid/base regulation:
kidneys generate and reclaim filtered bicarbonate, as well as secrete excess acid to maintain balance.
4. Balance of other electrolytes (Ca++, Mg++, Phosphate PO4 3-)

12. B. Non-excretory functions Renin-angiotensin mechanism to control BP
Kidney senses decreased BP
Secretes renin (enzyme), which converts Angiotensin I to angiotensin II
Angiotensin II is a vasoconstrictor  increased BP
Angiotensin II also stimulates aldosterone secretion
Aldosterone increases Na+ and H2O reabsorption, increased plasma volume, and increased BP (aldosterone also stimulates potassium secretion into tubules)

13. 2. Produces erythropoietin
Stimulates erythropoiesis in bone marrow
b. The anemia of CRF is primarily caused by impaired erythropoiesis
c.  RBC formation is mainly due to  erythropoietin production in the diseased kidneys, although other compounds that accumulate in renal failure may also suppress erythropoiesis.

14. 3. Maintains Calcium-Phosphorus bone homeostasis
Activates Vitamin D (Hydroxylation of 25-OH-D3 to 1,25-OH-D3) in kidney disease, can supplement calcitriol, but very expensive Low vit. D  less Ca++ absorbed
b. Inverse relationship between Ca++ and P, so when P is retained by diseased kidney, Ca++ levels decline (less calcium reabsorbed by the kidney).
c. Low serum calcium  parathyroid gland releases PTH: Parathyroid Hormone: works to elevate serum Ca++ by pulling it from the bones  fragility, muscular weakness, decreased muscular tone, and general neuromuscular hypoexcitability.

15. Kidney Disease
Nephritic Syndrome: group of diseases characterized by glomerular inflammation (glomerulonephritis)
Hematuria, HTN, mild  in renal fx.
Caused by infection, SLE, other causes
Acute: either resolves or  nephrotic syndrome or ESRD.
MNT: maintain good nutr. Status
(no restriction of prot/K+)
If HTN, restrict Na+

16. II. Nephrotic Syndrome: symptoms resulting from decreased glomerular function.
Glomerular capillary permeability increases markedly (and probably capillary permeability throughout the body)
Often an early sign of renal failure, especially in diabetes.

17. A. Characterized by: Proteinuria
(hallmark of nephrotic syndrome) – urinary protein loss of >3g/day
(2’ increased capillary permeability)
a. Hypoalbuminemia
b. loss of immunoglobulins
c. loss of transferrin
d. loss of vitamin D binding protein

18. 2. Edema 2’ 3. Hyperlipidemia 4. Also possible:
blood coagulation disorders or increased clotting (can  occlusions in lungs and legs)

19. B. Possible causes:
1. SLE, glomerulonephritis
2. Infections
3. diabetes mellitus
4. drugs/toxins
5. lipid nephrosis (more rare, seen in kids) lipid deposited in kidney tissue.

20. C. Nutrition Therapy
Energy:
High protein not recommended; accelerates kidney failure. RDA is appropriate.
Fat:
Sodium:

21. III. Acute Renal Failure (ARF):
Sudden drop in GFR. Can develop in a previously healthy person, and last from a few days to several weeks.
A. Causes
Prerenal: sudden drop in blood volume or renal bloodflow due to severe dehydration, shock or trauma.
Intrinsic: damage to kidney cells 2’ sustained shock, trauma, surgery, septicemia, nephrotoxic agents, acute glomerulonephritis.
Postrenal: (obstructive) Kidneys can form urine, but excretion is impeded.

22. B. Consequences
Uremic Syndrome:
Azotemia: accumulation of nitrogenous metabolites in the blood:
Uremia: azotemia plus the clinical signs and symptoms of weakness, ill feeling, n/v/d, itching (pruritis 2’ Ca, Na deposition), muscle cramps, hiccups, twitching, emotional irritability,  mental capacity.

23. 2. Proteinuria
3. Hyperkalemia (2’  clearance; nephropathy can cause deficiency in or resistance to aldosterone)
4. Sodium: sodium retention resulting in fluid retention, HTN, edema, CHF.
Some patients experience loss of high amounts of sodium: salt losing enteropathy.
5. Hyperphosphatemia
6. Acid-base balance:  uric acid secretion and bicarbonate production  metabolic acidosis

24. 7. Blood volume changes
Oliguric phase: very little urinary output – blood pressure rises sharply. Can  pulmonary edema (remember from HTN chapter)
Diuretic phase: large losses of fluids and electrolytes
Recovery phase: (hopefully) – everything normalizes.

25. C. Treatment
1. Treat underlying disorder
2. Nutrition Therapy
High Energy 2’ hypermetabolism
Protein: depends on renal function
No dialysis:
Dialysis:

26. c. Fluid: restricted to urinary output ml for insensible losses (losses via lungs and skin). Increase if v/d/fever
d. Potassium:
e. Sodium:
3. Drugs
Diuretics during oliguric phase
Exchange resins: cause Na+ to be exchanged for K+ in the colon so K+ is excreted.
Insulin: DM, and moves K+ into cells w/glucose

27. IV. Chronic Kidney Disease (CKD, previouslyCRF):
Irreversible, progressive destruction of nephrons. Leads to End Stage Renal Disease (ESRD) .
A. Causes
ARF
Nephritis, renal artery obstruction, kidney stones, nephrotic syndrome, polycystic kidney disease
Diabetic nephropathy
HTN, atherosclerosis

30. Kidney damage with normal or  GFR  renal reserve, but asymptomatic
B. Progression
Magnification Phenomenon: As GFR falls,  function of remaining nephrons (adaptive hypertrophy)
This is why it can go undetected. At Stage I: Protein restriction and conservative management can slow progression to ESRD. Control HTH and DM.
Kidney damage with normal or  GFR
 renal reserve, but asymptomatic
BUN, lytes,fluid balance, P, Ca++ ALL NORMAL

31. Renal Insufficiency
Mild azotemia (mildly increased BUN, creat)
Impaired concentration of urine: urine output is probably OK at this point, but because concentrating ability is impaired, we see nocturia
Mild anemia
Fatigue and decreased mental acuity
Challenges will accelerate renal deterioration (ie. excessive protein load, P load, or uncontrolled HTN, DM, etc.)

32. 4. Frank Renal Failure
Anemia (normochromic normocytic, but low Hgb/Hct)
Uremia
Poss. GI ulceration and bleeding
Skin: may become yellowed. Urea from sweat may crystallize on skin = uremic frost. Pruritis (itching)
PEM 
HTN

33. Hyperphosphatemia, poss. hyperkalemia Metabolic Acidosis
g. Hypertriglyceridemia
Hypocalcemia
Hyperphosphatemia, poss. hyperkalemia
Metabolic Acidosis
Fixed urinary output
Edema
Altered bone metabolism - Renal osteodystrophy

34. 5. ESRD End-Stage Renal Disease: GFR <20% of normal
Uremia
Kidney replacement therapy required (dialysis or transplant)
Others: hyperchloremia, hypermagnesemia, hyperuricemia

35. V. Treatment of CKD
Goal: delay progression of renal failure, prevent buildup of toxic metabolites, maintain or improve nutrition status, control symptoms.
A. Diet (see handout)

36. B. Hemodialysis (HD)
Method of purifying the blood in patients w/renal failure (GFR 4-5 ml/min). Takes over 2 main kidney functions:
·  Waste removal
·  Fluid removal

37. The two major forms of dialysis are hemodialysis and peritoneal dialysis. In hemodialysis, the patient’s blood is sent through a machine that filters away waste products. The clean blood is returned to the body. Hemodialysis is usually performed at a dialysis center three times per week for 3 to 4 hours.

38. In peritoneal dialysis, a fluid (the dialysate) is dripped into the abdomen. The dialysate captures the waste products from the blood, and after a few hours is drained away. Then, a fresh bag of dialysate is used. Patients using continuous ambulatory peritoneal dialysis (CAPD), the most common form of peritoneal dialysis, change dialysate four times a day. Another form of peritoneal dialysis, however, can be performed at night with a machine that drains and refills the abdomen automatically. Patients can perform peritoneal dialysis themselves.

39. VI. Consequences of CKD Osteodystrophies: Cardiovascular Disease
 P retention leads to  serum Ca++ with PTH secretion. Results in Ca++ being removed from bones. Also in renal failure:  intestinal absorption of Ca++
Tendency toward spontaneous fractures, painful joints, bone pain, metastatc calcification.
Cardiovascular Disease
Atherosclerosis: accelerated in CRF.  TG, esp w/HD
HTN due to Na+ and fluid retention, as well as alteration in renin-angiotensin mechanism
Pericarditis: etiology unknown

40. Hematologic abnormalities: :
Anemia is almost universal
EPO, Fe Cardiovascular Disease
GI disorders:
Loss of appetite, n/v, may also see changes in GI motility and absorption; GI hemorrhage
Neuropathy:
CNS manifestations:” fatigue, insomnia, depression, agitation; also convulsions, coma, and death
“dialysis dementia,” related to aluminum