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Water Metabolism and the Kidneys

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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:

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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

Urine

Na 69 mmol/l 40mmol/l

Urea 150 mmol/l 13,75 -24,2 mmol/l

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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?

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Water metabolism

• Total body water

• Compartments

• Water metabolism

• Regulation of water metabolism

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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

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Functional unit - Nephron

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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

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?

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

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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

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Nephrotic syndrome(proteinuria 3,5 g/day)

Glomerular membrane injury

Proteinuria

Liver metabolism

Dyslipidaemia

aterogenesis

Generalised edema Thrombogenesis

↓ Circulating volume

Toxic injury to tubules

Glomerular membrane injury

Proteinuria

Liver metabolism

Dyslipidaemia

aterogenesis

Generalised edema Thrombogenesis

↓ Circulating volume

albumin loss

oncotic pressure

Water and Na+ retention(sympathetic activity, ADH, aldosteron)

lipid metabolism

transport proteins

Ab, acute phase p.

anticoagulant proteins

fibrinogen production

Toxic injury to tubules

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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

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Glomerular disease

Vascular damage Altered filtration

Tubular ischemia Reabsorption of noxious molecules

Release of cytokines, proteinases, adhesion molecules, gr. factors

Changed cell. balance

Fibroblast proliferation Matrix deposition

Recruitment of Ag. activated cells

Progressive loss of renal function

Tubular atrophy Interstitial fibrosis Interstitial infiltrates

Chronic tubular cell injury

Tubular dysfunction, capillary perfusion

Development of chronic tubulointerstitial disease

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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

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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

Urine

Na 69 mmol/l 40mmol/l

Urea 150 mmol/l 13,75 -24,2 mmol/l

• Why does the patient have Kussmaul’s breathing? • Explain why the patient has the potassium concentration

so high?

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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.

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.

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

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Questions:

A 29 year old man with a history of bipolar (manic-depressive) 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?

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Kidney failure

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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

intrarenal

postrenal

Only changed function = Prerenal azotemia

Kidney failure with morphological changes of tubules

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Acute renal failure - differential diagnosis Feature/Type Prerenal Intrarenal Postrenal Mechanism

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 Increased Normal Normal

Increased ADH may

increase urea reabsorption

only in functioning tubules

Urinary Na+ 20 mmol/l 40 mmo/l 40 mmo/l

Aldosterone decreases urinary sodium (may act only in functioning tubules)

Urine creatinine

: serum creatinin 40 : 1 20 : 1 20 : 1

Increased urine concentration in prerenal failure (functioning tubules)

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 1% 1 -2 % 1 -2 %

Aldosterone decreases sodium excretion (may act only in functioning tubules)

Urine sediment Normal Casts, cellular debris,

proteinuria Variable Damaged tubules

Urinary RBC - 2-4 Variable Damaged tubules

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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

Urine

Na 69 mmol/l 40mmol/l

Urea 150 mmol/l 13,75 -24,2 mmol/l

• Which type of acute kidney failure does the patient suffer? Explain.

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Stages of acute renal failure

• Oligouric – anuric• Decreased water output, waste products and iones in excess

↑ BP, edemas, urea, hyperkalemia, metabolic acidosis

• Polyuric• Loss of great volumes of not concetrated urine, loss of ions Shock, cardiac failure

• Recovery or chronic renal failure

Uremia (Uremic syndrome):↑ urea, creatinin, uric acid, ↑ K+, Acidosis, (↑ PTH)

GIT signs: nausea, vomiting, anorexia, bloody diarrhoea

Hemorrhagic diathesis: bleeding (thrombocytes)

CNS signs, P(eripheral)NS signs

Cardiovascular signs

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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)

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Stages:

• Kidney (renal) impairmentGFR 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..

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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

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Chronic renal failure - consequences

glomerular filtration rateNephron damage or loss

kidney perfusion

Failure of kidney function

Failing endocrine functions:

secretion of EPO

insulinase secretion ( gluconeogenesis)

PTH catabolism

Anemia

Renal osteopathy

vitamin D3activation

Metabolic acidosis

Failing excretory

functions:

retention of

Sodium and water

K+

H+

Urea

Phosphate PTH secretion

Uric acid

Oliguria, anuria

Edema

Hyperkalemia

Uremic syndrome

Gout

Hypertension

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Causes of renal anemia

decreased erythropoetinchronic blood losshaemolysisiron deficiencyprotein deficiency (diet)vitamin B12 or folate deficiencychronic infection or inflammationhyperparathyroidismbone marrow infiltrationpure red cell aplasiaaluminium toxicitymalignancy

Direct effect of failing kidneys

Malabsorption, diet

Indirect effect of kidney failure

Effect of ↑ PTH

Others

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Loss of nephron mass

renal biosynthetic capacity

renal production of calcitriol

Gut calcium absorption

Renal excretory function

Retention of toxic metabolites

Metabolic acidosis

Hyper-phosphatemia

Hypocalcemia

PTH secretion

Osteitis fibrosacystica

Remodelling and redistribution of bone -Osteosklerosis

Metastatic calcification

Calcium x phosphate ballance failureDissolution of

bone buffers

Bone decalcification

+Osteoporosis

Protein-caloric malnutrition

Impaired bone growth in children(renal rickets)

Responsiveness of the bone to

calcitriol

Osteomalatia

Aluminium toxicity

Pathogenesis of bone disease in chronic renal failure

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A 58 year-old female who underwent surgery

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

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.

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?

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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)

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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?

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Renal anemia

Hemoglobine 110 -120 g/l

Normochromic, Normocytic