Transcript Water Metabolism and the Kidneys

Water Metabolism and the
Kidneys
1
A 70-year-old woman
A 70 year old woman was admitted for terminal care. Her
daughter found her unconscious in the house when the
patient has not been answering the phone for three
days.
It was warm in the house, so the patient had no
hypothermia.
The patient was unconscious, markedly dehydrated and
had Kussmaul’s (acidotic) respiration.
Plasma and urine electrolytes revealed:
2
A 70-year-old woman
Plasma
Standart
Na
137 mmol/l
135-145
mmol/l
K
8.7 mmol/l
3.6-5.0
mmol/l
Cl
103 mmol/l
98-106
mmol/l
Bicarb.
8 mmol/l
22-32
mmol/l
Urea
78.9 mmol/l
3.0-7,5
mmol/l
Creatinine
650 umol/l
50-140
umol/l
Na
69 mmol/l
 40mmol/l
Urea
150 mmol/l
13,75 -24,2 mmol/l
Urine
3
A 70-year-old woman
Why was the patient dehydrated?
How has the patient’s diuresis changed?
Why?
Explain sodium metabolism in this
patient.
How the water metabolism changes in
older age?
4
Water metabolism
•
•
•
•
Total body water
Compartments
Water metabolism
Regulation of water metabolism
5
Kidney Functions
• Homeostatic
–
–
–
–
Water and ion metabolism
Blood pressure
Excretion of waste products, toxic substances and drugs
ABB
• Endocrine
–
–
–
–
(Renin)
Erythropoetin, Thrombopoetin
Kalcitriol
Degradation of PTH, insulin
• Metabolic
– Gluconeogenesis
6
Functional unit - Nephron
7
77-year-old woman
was sent to the ED after being seen at her local clinic for regular follow-up appointment. On routine
laboratory tests, her urea and creatinine were significantly increased above the baseline and her
physician was concerned. She is remarkably healthy for her age. Osteoarthritis and hypertension are
her only medical problems. Her medication includes Ibuprofen (2400 mg/per day) and ACE inhibitors.
Physical exam: moderate bilateral ankle edema
Na
142
135-145mmol/l
K
4,1
3.6-5.0 mmol/l
Cl
101
98-106
Bikarbonates
16
22-32 mmol/l
Urea
24.3
3 - 8 mmol/l
Creatinine
282
45 – 90 umol/l
Specific gravity of urine
Slightly increased
1001 -1031kg/m3
1.
Why was the physician afraid of her kidneys?
2.
What might be the cause of the patient’s ankle edema?
3.
Why might the patient have increased urea and creatinine?
4.
How can urinalysis help to distinguish between hypovolemia and kidney failure?
8
Glomerular dysfunction syndromes
• Nephritic syndrome
– A consequence of inflammation of the filtration
membrane - (edema, cellularisation, local membrane
defects)
– Proteinuria, hematuria, hypertension (edema)
• Hereditary nephritis: Alport‘s sy
• Acquired: acute or chronic
• Nephrotic syndrome
9
Nephrotic syndrome
(proteinuria 3,5 g/day)
Glomerular
Glomerularmembrane
membrane
injury
injury
Toxic injury to tubules
 transport proteins
Water and Na+ retention
Proteinuria
Proteinuria
Ab, acute phase p.
(sympathetic activity, ADH, aldosteron)
albumin loss
↓↓ Circulating
Circulating
volume
volume
Generalised
Generalised
edema
edema
 lipid metabolism
 oncotic pressure
Liver metabolism
metabolism
Liver
 anticoagulant proteins
Thrombogenesis
 Thrombogenesis
 fibrinogen production
Dyslipidaemia
Dyslipidaemia
 aterogenesis
aterogenesis
10
Tubulo-interstitial diseases
• Inherited
•
•
•
•
•
•
•
Renal diabetes insipidus
Renal diabetes mellitus
R. phosphate diabetes
Aminoaciduria (cystinuria, Hartnup‘s disease)
RTA I. – VI.
Polycystic kidney disease
Fanconi‘s syndrome
• Acquired
• Renal diabetes insipidus
• Chronic tubulointerstitial disease
• Acute tubular poisoning (Fanconi‘s sy)
• Acute tubular ischemia
11
Development of chronic tubulointerstitial disease
Glomerular disease
Vascular damage
Tubular ischemia
Altered filtration
Reabsorption of noxious molecules
Chronic tubular cell injury
Release of cytokines, proteinases, adhesion molecules, gr. factors
Changed cell.
balance
Tubular atrophy
Fibroblast proliferation
 Matrix deposition
Interstitial fibrosis
 Recruitment of
Ag. activated cells
Interstitial infiltrates
Tubular dysfunction,  capillary perfusion
Progressive loss of renal function
12
Consequences of kidney function failure:
• Before the kidney (in the body)
–
–
–
–
BP, edema
Hyperkalemia, hyperphospatemia
Azotemia, uremia, creatininemia; uricemia
Metabolic acidosis
• Behind the kidney (in urine)
– Specific weight, volume
– Content: proteins, blood, puyria, crystals, casts
13
Back to the 70-year-old woman
Plasma
Standart
Na
137 mmol/l
135-145
mmol/l
K
8.7 mmol/l
3.6-5.0
mmol/l
Cl
103 mmol/l
98-106
mmol/l
Bicarb.
8 mmol/l
22-32
mmol/l
Urea
78.9 mmol/l
3.0-7,5
mmol/l
Creatinine
650 umol/l
50-140
umol/l
Na
69 mmol/l
 40mmol/l
Urea
150 mmol/l
13,75 -24,2 mmol/l
Urine
• Why does the patient have Kussmaul’s breathing?
• Explain why the patient has the potassium concentration
so high?
14
A 29 year old man with a history of bipolar
(manic-depressive) disorder
has been treated with lithium for 7 years and now presents with progressive renal changes and new
onset orthostatic hypotension. Over the past year, the patient has experienced polyuria,
polydipsia and mild renal insuficiency with a serum creatinine level maintained near 150 umol/l
(normal 70 -120umol/l). There was no family history of renal disease.
On physical exam, the patient was afebrile, with a heart rate of 100 bpm and a blood pressure of
120/90.
Urine specific gravity
1.007
1001 -1031 kg/m3
Urea
17,85
3 - 8 mmol/l
Serum creatinine
353,6
45 – 90 umol/l; 70-120umol/l men
Serum sodium
158
135-145
mmol/l
Important negative findings:
• Erythrocyte sedimentation rate and IgA levels were not elevated.
• Serum complement was not decreased and a test for anti-nuclear antibodies was negative.
• An intravenous pyelogram and renal ultrasound were normal.
15
Questions:
A 29 year old man with a history of bipolar (manicdepressive) disorder
•
What are the most important laboratory findings?
•
What is the patient‘s primary problem?
•
Does the patient have prerenal azotemia?
•
Why are the negative findings important?
16
Kidney failure
17
Acute renal failure
„is a sudden loss of the ability of the kidneys to remove
waste products and concentrate urine without losing
electrolytes“
Types:
prerenal
Only changed function
= Prerenal azotemia
intrarenal
postrenal
Kidney failure with
morphological changes of
tubules
18
Acute renal failure - differential diagnosis
Feature/Type
Prerenal
Intrarenal
Postrenal
History
Volume depletion
Heart failure
Ischemic episodes
Nefrotoxins, Vasculitis
Kidney stones
Tumor, Prostate
hyperplasia
Mechanism of
failure
development
Hypoperfusion of
tubules
Severe ischemic or
toxic tubular damage
Increased
intratubular pressure
Serum urea : serum
creatinine ratio
Urinary Na+
Increased
 20 mmol/l
Normal
 40 mmo/l
Mechanism
Normal
Increased ADH may
increase urea reabsorption
only in functioning tubules
 40 mmo/l
Aldosterone decreases
urinary sodium (may act
only in functioning tubules)
Urine creatinine
: serum creatinin
40 : 1
20 : 1
20 : 1
Urine osmolality :
serum osmolality
 1,5 : 1
 1,3 : 1
 1,3 : 1
Kidneys are able to
concentrate urine only in
functioning tubules
Fractional excretion
of sodium
Urine sediment
Urinary RBC
Increased urine
concentration in prerenal
failure (functioning tubules)
 1%
 1 -2 %
 1 -2 %
Aldosterone decreases
sodium excretion (may act
only in functioning tubules)
Normal
Casts, cellular debris,
proteinuria
Variable
Damaged tubules
-
2-4
Variable
Damaged tubules
19
Back to the 70-year-old woman
Plasma
Standart
Na
137 mmol/l
135-145
mmol/l
K
8.7 mmol/l
3.6-5.0
mmol/l
Cl
103 mmol/l
98-106
mmol/l
Bicarb.
8 mmol/l
22-32
mmol/l
Urea
78.9 mmol/l
3.0-7,5
mmol/l
Creatinine
650 umol/l
50-140
umol/l
Na
69 mmol/l
 40mmol/l
Urea
150 mmol/l
13,75 -24,2 mmol/l
Urine
• Which
type of acute kidney failure does the patient suffer?
Explain.
20
Stages of acute renal failure
• Oligouric – anuric
• Decreased water output, waste products and iones in excess
 ↑ BP, edemas, urea, hyperkalemia, metabolic acidosis
(Uremic syndrome):
•Uremia
Polyuric
↑ urea, •creatinin,
Loss ofuric
great
acid,
volumes
↑ K+, Acidosis,
of not concetrated
(↑ PTH) urine, loss of ions
 Shock,
 GIT
signs: cardiac
nausea,failure
vomiting, anorexia, bloody diarrhoea
 Hemorrhagic diathesis: bleeding (thrombocytes)
 CNS signs, P(eripheral)NS signs
• Recovery or chronic renal failure
 Cardiovascular signs
21
Chronic renal failure (CRF)
„Chronic kidney disease is the slow loss of kidney function
over time due to chronic loss of nephrons.“
Causes: all chronic diseases
(hypertension, diabetes, infections, vasculitis,
tubulointerstitial diseases, glomerulonephritis, polycystic
kidney disease, amyloidosis)
22
Stages:
• Kidney (renal) impairment
GFR 25 – 50 ml/min
 Polyuria, nykturia, izostenuria
• Kidney isuficiency
GFR 20 ml/min
 Anemia, osteopathy, azotemia x diet compensate homeostasis
• Kidney failure (End Stage Renal Disease (ESRD))
GFR less than 10 ml/min
 Uremic syndrome, anemia, osteopathy ..hyperkalemia, acidosis..
23
Another stageing of chronic renal failure
Stage
GFR (ml/min/1.73m2) Description
1
> 90
Normal or increased GFR, with other
evidence of kidney damage
2
60–89
Slight decrease in GFR, with other
evidence of kidney damage
3
30–59
Moderate decrease in GFR, with or without
other evidence of kidney damage
4
15–29
Severe decrease in GFR, with or without
other evidence of kidney damage
5
< 15
Established renal failure
24
Chronic renal failure - consequences
Nephron
damage
or loss
 glomerular filtration rate
Failing
excretory
functions:
 kidney perfusion
 retention of
Failure of kidney function
Oliguria, anuria
Hypertension
Sodium
and
water
Edema
Failing endocrine
functions:
 secretion of EPO
Hyperkalemia
Anemia
 insulinase secretion
( gluconeogenesis)
 PTH catabolism
 vitamin D3activation
Uremic syndrome
Gout
Metabolic acidosis
Renal osteopathy
 PTH
secretion
K+
Urea
Uric acid
H+
Phosphate
25
Causes of renal anemia
decreased erythropoetin
chronic blood loss
haemolysis
iron deficiency
protein deficiency (diet)
vitamin B12 or folate deficiency
chronic infection or inflammation
hyperparathyroidism
bone marrow infiltration
pure red cell aplasia
aluminium toxicity
malignancy
Direct effect of failing
kidneys
Malabsorption, diet
Indirect effect of kidney
failure
Effect of ↑ PTH
Others
26
Pathogenesis of bone disease in chronic renal failure
Loss of nephron mass
 Renal excretory function
 renal biosynthetic capacity
 renal production of
calcitriol
Retention of toxic
metabolites
Metabolic
acidosis
Hyperphosphatemia
Hypocalcemia
Proteincaloric
malnutrition
 Gut calcium
absorption
Aluminium
toxicity
Impaired bone
growth in
children
(renal rickets)
 Responsiveness
of the bone to
calcitriol
Osteomalatia
Dissolution of
bone buffers
Bone
decalcification
+Osteoporosis
 PTH secretion
Remodelling and
redistribution of
bone Osteosklerosis
Osteitis
fibrosa
cystica
Calcium x
phosphate
ballance
failure
Metastatic
calcification
28
A 58 year-old female who underwent surgery
developed hypotension requiring aggressive fluid resuscitation. Three days
later the patient weighs 20 kg more than pre-operatively. She is on a
ventilator and is oliguric. Her urine output has been about 300 ml per 24
hours.
Na+
140
135-145mmol/l
K+
5,7
3.6-5.0 mmol/l
Cl-
102
98-106
Bicarbonates
20
22-32 mmol/l
Urea
16,7
3 - 8 mmol/l
Creatinine
300,5
45 – 90 umol/l
Urine sodium
41
30 – 170 mmol/l

What type of kidney failure has she developed?

Why has her weight increased ? List all mechanisms.

What could you find in this patient on physical exam?

Why the potassium levels in this patient are so high? What are the risks of
this finding? How could you quickly lower its level?
29
A 44-old-year patient 14 years following an episode of
glomerulonephritis
LH is a 44-old-year patient who has been receiving continuous ambulatory peritoneal
dialysis for 14 years following an episode of glomerulonephritis. She has stopped her
part-time job for overall feelings of fatigue. She is said to be poorly compliant with her
diet and medications.
Physically: height 160 cm, weight 62 kg, BP 125/85, P 90
albumin
23
35 – 50g/l
Na+
135
135-145mmol/l
K+
6,9
3.6-5.0 mmol/l
Cl-
100
98-106
Bicarbonates
16
22-32 mmol/l
Urea
16,1
3 - 8 mmol/l
Creatinine
300,5
45 – 90 umol/l
Urine sodium
41
30 – 170 mmol/l
Ca++
1,95
2,25 – 2,75 mmol/l
Hemoglobin
70
12-15 g/l (female)
PO43-
2,3
0,7 – 1,5 mmol/l
Hematocrit
22
35-42% (female)
30
A 44-old-year patient 14 years following an
episode of glomerulonephritis
 What might be responsible for the patient‘s fatique?
 Which signs of complications of chronic renal failure could you see in this
patient?
 An ECG reveals peaked T-waves, extremely widened QRS complexes and
occasional extrasystoles. Which value is responsible for this findings and
how could you help the patient?
 Which factors may contribute to the development of her renal osteopathy?
 What specific gravity of urine do you expect in our patient? Why?
 LH was placed on erythropoetin three months ago. Her hemoglobin (7
mmol/l) and hematocrit (22 mmol/l) are even low now. What could be the
reason?
31
32
Renal anemia
Hemoglobine 110 -120 g/l
Normochromic, Normocytic
33