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41
Uric acid
Serum concentration: 1.5-5mg/dL
Consequences of the
hyperuricaemia in CRF:
CKD progression
Vascular disease
pathogenesis
Pericarditis pathogenesis
seldom, secondary gout
42
Uraemic toxins retention syndrome
Fluid and electrolytes disorders
Acido-basic balance disorders
Metabolic disorders
Patho-physiology CRF syndromes
43
Water balance disorders in CRF
Normal distribution of water
From total From body Litri
water (%) weight (%)
Total water 100 60 42L
Intracellular 55 33 23L
Extracelullar 45 27 19L
Interstitial fluid 20 9L
Plasma 7.5 3L
Conective tissue 7.5 3L
Bone 7.5 3L
Transcelullar water 2.5 1L
During CRF:
Total water increases
Interstitial water increases
Intravascular water decreases
Intracellular water increases
44
Water balance disorders in CRF
Extracelullar dehydration
(most frequent disorder)
Hyperhydration (global/extracelullar):
1. Nephrotic syndrome
2. Liver cirrhosis
3. Heart failure
4. Iathrogenic
45
Sodium balance disorders in CRF
A) Negative sodium balance -
the most frequent disorder in CRF
Mechanism: renal sodium loss (as a result of increased
fractional sodium excretion)
Consequences:
Sodium depletion
Reduced sodium intake Increased sodium losses
Vomiting Anorrhexia
Extracelullar hypoosmolarity
46
Sodium balance disorders in CRF
B) Positive sodium balance
Mechanisms:
1. Decreased GFR
2. Hyperaldosteronism
3. Increased pressure in urinary tract (obstruction)
Consequences:
water retention resulting in hyperhydration
47
Potassium in CRF - hyperkalaemia (>5.2mEq/L)
Causes and mechanisms
1. Intake of >60-90 mEq K
+
/day
food intake
drugs
2. Reduction of renal excretion of K
+
:
a) GFR reduction (oliguria)
b) Reversible reduction of tubular secretion:
- reduced sodium in distal nephron: hyponatraemia, dehydration;
- potassium -sparing diuretics (amilorid, triamteren)
c) hypoaldosteronism:
- deficient synthesis (CSR insufficiency)
- reduction of aldosteron synthesis stimulation
(i) reduced synthesis of renin (IN, DM, elderly, NSAID)
(ii) reduced angiotensin (ACEI, ARB, betablockers)
(iii) aldosteron antagonists (spironolactone)
d) Reduction of tubular response to aldosteron:
- amiloidosis, IN (sickle-cell disease, SLE), renal graft rejection
48
Potassium in CRF - hyperkalaemia (>5.2mEq/L)
Causes and mechanisms
3. Changes of the K
+
distribution
a) Acidosis
b) Hypoxia
c) Tissue damage
d) Hypercatabolism
e) Anti-anabolism (tetraciclins)
Complaints:
Cardio-vascular Neuro-muscular Gastrointestinal
Bradicardia Paraesthesia Nausea
Arithmia Muscle weakness Vomiting
Weak cardiac sounds Lethargy Abdominal pain
Hypotension Ileus
49
Potassium in CRF - hypokalaemia (<3.5mEq/L)
Causes and mechanisms
1. Reduced intake of K
+
(diet, anorrhexia)
2. K
+
losses
a) Extrarenal (vomiting, diarrhaea, digestive fistula)
b) Renal:
- Increased renin: malignant hypertension, renovascular HT
- Reduced renin: primary hyperaldosteronism
- Variable renin: NS, CHF, liver cirrhosis, diuretics,
liquiritia/analogs
3. Changes in K
+
distribution:
- acute metabolic alkalosis
- excessive IV infusion of glucose+insulin
50
Potassium in CRF - hypokalaemia (<3.5mEq/L)
Complaints
1. Neuro-muscular:
Muscle weakness
Paresis, areflexia
Confusion, depression, lethargy
2. Gastrointestinal
Ileus and gastric dilatation
3. EKG
T isoelectric/biphasic
U wave
ST progressively depressed
High Pwave
Increased QT interval
Broadened QRS complex
AV conduction disorders
Tahiarithmias
PR QT
U
U
T
ST
QT
T
U
51
Calciul n IRC
METABOLISMUL NORMAL AL CALCIULUI
Aport alimentar: 1000 mg Ca/zi
Absorbie intestinal 350 mg mg Ca/zi
a) Activ (controlat de Vit D) - intestin proximal
b) Pasiv (independent de Vit D) - intestin distal
ABSORBIA NET = 200 mg/zi (150 mg Ca sunt resecretate)
Excreie
a) renal 150-300 mg/24 ore (controlat de PTH)
b) intestinal 600-800 mg/24 ore
Distribuie
Calciu osos 988 g
Calciu ic 11 g
Calciu ec 1 g
Calciul total 1000 g
Bilan intern
a) Se fixeaz n os 450 mg Ca/zi (sub controlul Vit D, CT)
b) Se elibereaz din os 450 mg Ca/zi (sub controlul PTH)
Calcemia 9-11 mg/dL (4.5-5.5 mEq/L)
52
Calcium in CRF
Hipocalcemia (<4,2mEq/L) + Hipocalciuria
Mechanisms of hipocalcemia
1) Low diet intake
2) Low enteral absorbtion:
a) Vit D deficiency
b) High Pi (sulphates) in gut secretions
c) Enteral uremic lesions
3) High serum Pi
4) Bone resistance to PTH actions
Mechanisms of hipocalciuria
Increased tubular reabsorbtion (high PTH)
Low filtred calcim (hipocalcemia, low GFR)
53
Phosphate in CRF
Hiperphosphatemia + Hipophosphaturia
Hiperphosphatemia mechanismsi
1) Low renal excretion (ClCr <35 mL/min)
2) High bone turn-over (secondary hiperparathyroidism)
3) High enteral phosphate absorbtion
Consequences
HIPOCALCEMIA &
SECONDARY HYPERPARATHYIROIDISM:
Reduced ionic calcium
Reduced calcium enteral absorbtion
1alpha-25OH Vit D hidroxylaze inhibition (active Vit D deficiency)
Bone resistance to calcemic action of PTH
54
Consequences of hiperphosphatemia
+ Ca
2+
+ Resistence
to PTH
| Resistence
to calcitriol
+ Calcitriol
| PTH
Parathyroides gl
Hipertrophy/hiperplasia
| Pi
Ectopic calcium deposits
55
| PTH | PTH
+ Ca
2+
+ 1.25 (OH)
2
D
3
| Pi
CKD
RENAL
OSTEODISTROPHY
SISTEMIC
TOXICITY
Sistem nervos
Heart & Vasels
Nervous system
Hematologycal
Imunologycal
Secondary hipeparathyrodism
56
Clincal Consequences
1) Renal osteodystrophy
2) Grotw retardation
3) Calcificri Ectopic calcium deposits
4) Increased excitabity
No tetany, because:
a) Ionic calcium does not decrease (acidosis)
b) Unmodificed Szent Gorgy ratio
+ +
+ + +
OH Mg Ca
H K Na
2 2
57
Uraemic toxins retention syndrome
Fluid and electrolytes disorders
Acido-basic balance disorders
Metabolic disorders
Patho-physiology CRF syndromes
58
Normal AB balance
Normal pH 7.35-7.45 (6.8-8)
Kidney:
Excrets 60-90 mEq H
+
daily (1mEq H
+
/kg), produced by
metabolism as:
Ammonium ions ionilor de amoniu (60%)
Titrable acidity (40%)
Bicarbonate reasorbtion
59
AB balance in CRF
METABOLIC ACIDOSIS (the most common situation)
Mechanisms:
Reduced ammoniogenesis
Reduced titrable acidity (GFR<20 mL/min)
Reduced bicarbonate reabsorbtion
Retention of non-volatile acids
Consequences:
Blood pH 7.3-7.2; HCO
3
-
12-15 mEq/L; HA 15 mEq/L
Acidotic dispneea
Decreased AP
Coma, seizures
Increased dissociation of oxyhaemoglobine
Increased [ionic calcium]
60
Uraemic toxins retention syndrome
Fluid and electrolytes disorders
Acido-basic balance disorders
Metabolic disorders
Patho-physiology CRF syndromes
61
A) GLUCIDS
Uremic pseudo-diabetes - 50-55% of pts
Abnormal glucose uptake
Increased neoglucogensis
Hiperinsulinism
Normal fasting blood sugar
Severe hipoglicemia (rarely)
B) LIPIDS Accelated atherosclerosis
Hipertrigliceridemia, normal colesterol, free faty acids
Abnormal lipoprotein composition:
Increased TG concentration in all LP clases
Colesterol redistribution : low HDL colesterol
C) PROTEINS Malnutrition
Protein intolerance
Nitrogen balance is preserved for long time, because the protein
requirements are lower in uremia
Metabolic disorders
62
Manifestrile clinice ale IRC
63
Manifestrile clinice ale uremiei
NEUROLOGIC
Cefalee, apoplexie (AVC, hematom subdural ),
oboseal, letargie, com, insomnii /somnolen,
iritabilitate muscular, asterixis,
Sd. de dezechilibru osmotic, crize convulsive,
mioclonii , encefalopatie uremic sau aluminic
RESPIRATOR
Dispnee Ksmaul, respiraie Cheyne-Stokes
Plmnul uremic, Pneumopatii acute
Pleurezie
GASTROINTESTINAL-PANCREATIC-HEPATIC
Gur uscat, grea, vrsturi , foetor uremic,
stomatit , gingivite, glosit, parotidite, anorexie,
gastroenterite, ulcus gastro-duodenal, sngerri
digestive, colici intestinale , diaree
Insuficien pancreatic, pancreatit
Alterri ale funciilor metabolice hepatice
Hepatite virale B i C
HEMATOLOGIC
Anemie normocrom, normocitar
Leucocitoz moderat
Sindrom hemoragipar mixt
NEUROPATIE PERIFERIC
Sd. gambelor nelini tite, burning feet syndrom,
parestezii, hiperreflectivitate, contracturi muscu-
lare, sughi , paralizie
Sd. de tunel carpian
IMUNOLOGIC
Deficit imunitar
Infecii bacteriene i virale
PSIHIC
Euforie nemotivat, depresie,
astenie, anxietate, demen, psihoz
OCULAR
Sd. de ochi roii, conjunctivit,
keratit, calcificri pericorneene,
retinopatie hipertensiv
ENDOCRIN
Hiperparatiroidism secundar
Tulburri gonadice:
- amenoree, infertilitate
- disfuncie sexual, impoten
- pierderea libidoului, aspermie
Insulin, glucagon |
Disfuncii tiroidiene
CARDIOVASCULAR
HTA, pericardit, cardiomiopatia
Ateroscleroz, IVS acut, IC
Aritmii diverse
DERMATOLOGIC
Uscciunea tegumentelor, paloare
tegumentar cu tent murdar,
pigmentare (semn Terry), prurit, chi-
ciura uremic, echimo-ze,erupii di -
verse, edeme faciale i la glezne0
BIOCHIMIC
Produi retenie azotat crescui
Alterri ale ionogramei sanguine ( Na+,
K+, hipocalcemie, hiperfosfatemie),
acidoz metabolic, Cluree ,
Cl
Cr
, Cl
PAH
sczute
URINA
Oligurie, nicturie
Izo-/subizostenurie
Proteinurie
Leucociturie
Cilindrurie
Infecii urinare
Litiaz
METABOLIC
Deshidratare, rareori hiperhidratare,
Intoleran la glucide, hiperlipoproteinemie,
Malnutri ie protein-caloric
Dureri osoase, gut, condrocalcinoz
osteodistrofie, osteomalacie (carenial, aluminic),
amiloidoza beta2-microglobulinic
Hipotermie
IRC
PRINCIPALELE MANIFESTRI
IRC IRC
PRINCIPALELE MANIFESTRI PRINCIPALELE MANIFESTRI
64
Digestive tract
Mouth
Foetor
Glositis
Gingivitis
Stomatitis
Parotiditis: uni-/bilateral
Stomach Uremic gastritis
Enteral Uremic enterocolitis
Pancreas - Pancreatitis
Liver
Hepatosis
Hepatitis
Hemochromatosis
Mechanisms
Nitrogen retention
Urea NH
3
Urea + NH
3
=ammonium carbamate
Electolites disorders
Substrate
inflammation
bleeding
necrosis perforation
65
Cardio-vascular
HBP
Prevalence - 70-80% at RRT initiation
Mechanisms
Hypervolemia (water and sodium retention)
RA A system hiperactivity
Hyper catecholaminaemia
Endotelium dysfunction:
ET
+ NO (NOS inhibition)
+ Production of PG, KK, FNA
Blood vessels hyperactivity at vassoconstrictors (increased Na
+
content of arterial walls)
Increased intracellular Ca
2+
(?)
Na
+
K
+
-ATP-aze inhibitors (?)
Others (drugs, + compliance of arteries)
66
Cardio-vascular
hBP
Mechanisms
Hypovolemia
Anti hypertensive drugs
Systolic myocardial dysfunction
Vegetative dysfunction - polyneuropathy
Pericarditis
Pericarditis - death bell in uremia - R Bright, 1827
Frequency - 30% of pts
Presentation:
sero-fibrinous (small exudate)
Uremic cardiomyopathy
Frequency - 66% of pts
Mechanism:
myocardial response to: HBP, anemia, volume expansion etc.
Presentation
LVH, LV dilatation, systolic disfunction
67
Lungs
Dyspnea
sine materia - Kssmaul
Cheyne-Stockes
Uremic lung
Mechanisms
Volume expansion, HBP, heart failure
Uremic toxins, hypoxia, anemia
Hypoproteinemia
Immunologyc mechanisms
Alteration in alveolar surfactant
Pathology
Interstitial and intra-alveolar exudate
Cellular reaction
Presentation:
Dyspnea + discrepan grad dispnee - examen obiectiv
Rx: butterfly bilateral unhomogenous infiltrates
Uremic pleuritis
68
Nervous system
UREMIC ENCEPHALOPATHY
Pathology:
Acid-base and electrolites abnormalities
Osmotic disequilibrium
Brain edema (HBP)
Drugs adverse effect
Secondary hyperparathyroidism, Aluminium toxicity
Presentation:
Sleep disorders, irritability, anxiety, delirium, coma
Disartria, asterixis, myoclonus, seizures
EEG: alpha waves with lower frequency and higher
amplitude + rapid complexes peak-wave
69
Nervous system
UREMIC POLYINEUROPATHY
Pathology:
Axonal enzymes dysfunction which can not be aleviated by
neuronal body
Produced by:
Middle molecules
Myoinozitol, methyilguanine
Calcium
Tiamine deficiency
Demyelination of long nerves, retrograde neuronal
degeneration
Presentation:
Sensy-motor, symmetrical, distal (lower limbs), slowly
progressive (centripetal)
VCN <40 m/sec
EMG
70
Endocrine glands
SECONDARY HYPERPARATHYIROIDISM
Renal osteodystrophy
Ectopic calcium deposits
Ca x Pi >55mg
2
dL
2
Sites
Articulary, periarticulary - McCarthy pseudogout
Ocular (conjunctival, cornea) red eyes
Skin - pruritus
Vascular (subintimally or medial)
Parenchimatous (myocardial, kidney etc)
71
Renal bone disease
Others
(Si, F, Fe etc)
Aluminium
intoxication
ODR
beta2
microglobuline
amyloidosis
72
Endocrine glands
Gonads
Male:
impotence
gynecomastia
Female:
dysmenorea
metrorrage
Both sexes:
Lower libido
Infertility
73
Renal Anemia
Erytrocytes
Normochromic, normocytic (seldom, macrocytosis or mycrocitosis)
Anizocytosis (schizocytes, sferocytes)
Poikilocytosis (burr cells)
Moderate severe (Hb7g/dL, Ht21-22%)
Well tolerated:
acidosis
Increased intracellular 2,3DPG concentration
Other charateristics:
Short E life span
Abnormal iron uptake by bone marrow
Reticulocytes
Inappropriate number for Hb level
White blood cells
Increased number even without infection !
Platelets
Normal number, functional abnormalities
Bone marrow:
Abnormal E maturation
74
Renal Anemia - Causes
1) Reduced production
a) Epo deficiency
b) Mielodepressive action of uremic toxins
c) Iron deficiency
d) Protein malnutrition
e) Blood transfusion
2) Reduced E life-span
a) Uremic millieu
b) Folic ac and Vit B12 deficiency
c) Microangyopathic hemolysis
3) Bleeding
a) Mostly GE
b) Blood for analysis (3.5 L/yr in HD pts)
75
Policitemia
Causes
Polycystosis
Hydronephrosis
Kidney tuberculosys
Renal tumors
76
Immunosupression
1. Increased frequency and gravity of infections
(tuberculosis included)
2. Low diagnostic value of skin tests
3. Lower rate of succes in vaccination
4. Higher cancer prevalence
5. Rapid evolution of bone and/or vascular disease
77
Skin
1) DIRTY PALLOR
1. Anemia
2. Vasoconstrition
3. Chromogen deposists
2) PRURITUS
1. Sebum glands atrophy
2. Abnormal composition of sweat (urea, lipids, AA)
3. Intrademic calcium deposits
4. Intradermic mastocytosis
5. Nerve ending alteration
3) UREMIDE
4) UREMIC FROST
78
Malnutrition
Low intake (calories + protein)
Increased catabolism
79
Treatment of CRF
Prophyfilaxis
80
Primary prophyaxis (nephropathies)
1) Diet
Water
NaCl
Calories and proteins
2) HBP
3) Proteinuria:
Pathogenetic therapy
ACEI, sartans)
4) Hyperlipoproteinemia
statins
fibrats
5) Anemia - epoietin
6) Hyperphosphatemia
7) Hyperuricemia
Secondary prophylaxis delaying progression
81
Diet
Calories - 30-35cal/kg zi
Glucids 4-5g/kg zi
Lipides 0.8-1 g/kg zi
Proteins
CRF Stage Proteins
(g/kg day)
Fully compensated 1
Compensated 0.5-0.6
Decompensated 25-30
Uremia 25-30
ESRD 1-1.2
82
Strategy to slow down progression
Targets
GFR decrease: <2mL/min per year
BP
<130/85mmHg (JNC VI)
<130/80mmHg (ADA) DZ
125/75mmg (JNC VI) DZ, IRC, proteinurie
Proteinuria
<0.5g/24 ore
LDL Colesterol
<100mg/dL (2.6mmol/L)
When to start ?
As early as possible
Is efficient even when GFR <30-10mL/min
Duration
Lifelong
83
Steps
1. Reduction of salt in diet
2. First drug
ACEI or sartans in small doses, follow up:
GFR (decrease <30%)
Kalium (increase <5.5mEq/L)
Proteinuria
Increase dosage till:
On target
Maximum allowed (tolerated) dosage
3. Second drug:
Diuretic
tiazidic (ClCr >30mL/min)
loop (ClCr 30-15mL/min)
Assocaition tiazidic + loop (ClCr <15mL/min)
84
Steps
4. Third drug
K <5.5mEq/L
Sartans or ACEI, accordingly CV (-)
Non-dihydroptiridinic calcium blocker CV (+)
K >5.5mEq/L
Non-dihydroptiridinic calcium bloker or
Beta blocker
Increase dosage till:
On target
Maximum allowed (tolerated) dosage
6. Forth drug if BP uncontrolled !
Non-dihydroptiridinic calcium blocker sau
Beta blocker
6. Fifth drug
Long acting dihydroptiridinic calcium bloker
7. Sixth drug
Alpha peripheral blocker
85
Steps
8. Probably efficient
Statins
Anti-aldosteronic diuretics
86
Tratamentul insuficienei renale cronice
Tratamentul patogenic
87
Mineral metabolism
TARGETS
Serum calcium
Total: 9.2-9.6 mg/dL
Ionic: 4.6-5.4 mg/dL
Serum phosphate
2.7-4.6 mg/dL (RFG >15mL/min)
3.5-5.5 mg/dL (RFG <15mL/min)
Calcium phosphorus product
< 55mg
2
/dL
2
iPTH
40-110pg/mL (GFR >15mL/min)
100-150pg/mL (GFR >15mL/min)
88
Mineral metabolism
1) Diet Ca/PO
4
2) Phosphatemia (5-6mg/dL) enteral phosphates binders:
Calcium carbonate (no more than 1,5g elemental calcium per
day)
Calcium acetate (maximum 1,2-1,5g elemental calcium per day);
Aluminium hydroxide/aluminiuim salts (only short courses)
Sevelamer hydrocloric (Renagel).
3) Calcium supplements
4) Active vit D derivates
- 1,25(OH)
2
D (calcitriol DCI, Rocaltrol