of 55
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Acid-base and hydromineral balance
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The distribution of water and
electrolytes in the body
Water content: fetus 95 - 85%, newborn 77%,
adults 50-60% (women contain more fat) Fluid compartments : - Extracellular fluid 14L
(blood plasma 3L, interstitial space 11 L)
- Intracellular fluid 28L 45% of theblood is represented bycellular
components, 55% is the plasma
Interstitial fluid ~ plasma, intracellular different
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The distribution of electrolytes in
the fluid compartments (mEq/l)Ions Blood plasma Interstitial fluid Cells
Cations: 153 153 195
Na+ 142 145 10
K+ 4 4 156
Ca2+ 5 2-3 3
Mg2+ 2 1-2 26
Anions: 153 153 195
Cl- 103 116 2
HCO3- 28 31 8
Proteins 17 0,2 55
Other anions (phosphates,
sulphates)
5 5,8 130
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Osmotic pressure
Osmotic pressure
Osmosis The osmolarity of
plasma is 300
mosmol/l
The distribution of
proteins cause the
oncotic pressureOsmotic pressure
Hydrostatic pressure
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The pH of the body
pH = - lg[H+], in the blood 7,357,45
Buffer systems, lungs, kidneys maintain the pH
Buffer: weak acid/base and its hydrolyzable salt
HCO3-/H2CO3, Hb2H
+/2K+Hb4O2,
Na2HPO4/NaH2PO4, protonated/deprotonated proteins
Buffering capacity: efficacy pH = pKa + lg[HCO3
-]/[H2CO3] (Henderson-
Hasselbalch ecuation)
pH = 6,1 + lg 20 = 6,1 + 1,3 = 7,4
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The kidney's role in maintaining
the internal balance 200 liters of water ar filtrated per day and 30 Eq Na+ Tubular resorption-> 1,5 l water, 0,1 Eq Na+ loss
Glomerular filtration: ultrafiltrate (H2O, NaCl, KCl, H,organic compounds), at the level ofproximal convolutedtubules water and salt are isoosmotically reabsorbed, in thedescending part of the Henle loop selective reabsorption ofwater takes place, in the ascending part selective
reabsorption of NaCl, the tubular fluid osmolarity decreases. In the distal tubules Na+ is reabsorbed, K+and H+ are
eliminated (aldosteron effect), here takes place the ADH-dependent reabsorption of H2O
The final hormonal regulation is in the collecting tubules
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The neuro-renal regulation of the
hydro-electrolytic balance Thirst affects water uptake
The increased osmolarity of the extracellular fluid compartment
causes water loss in the neurons of the hypothalamic thirst center
The decrease of the blood plasma volume has also excitatory
effect
The atrial and vascular baroreceptors have also regulatory effect The release of ADH in the kidney, which acts by cAMP, leads to
water retention
The tension of the atrial wall enhances ANP synthesis
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Hyper- and hypokalemia
The symptoms ofhyperkalemia are: bradycardia (low heart rate),muscle twitching, numbness. The values exceeding 9-10 mmol/lrepresent danger of cardiac arrest. Hyperkalemia over 5 mmol/loccurs most often in renal failure. Serum potassium is increased
inAddison\'s disease (adrenal insufficiency due to decreasedaldosterone secretion, thus the renal elimination of potassium isreduced). Hyperkalemia occurs in diabetic ketoacidosis (in theabsence of potassium insulin cannot enter muscle and fat cells),the massive destruction of tissue in shock.
Hypokalemiais manifested by: apathy, muscle weakness,reduced intestinal activity, tachycardia (increased heart rate).Hypokalaemia occurs in Cushing\'s syndrome (adrenalhyperfunction), very abundant diarrhea and vomiting, treatmentwith not sparing diuretics (such as loop diuretics).
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The role of lungs and erythrocytes
In the extrapulmonar tissues pCO2 is high, diffuses
into erythroc. CO2 + H2O -> H2CO3 -> HCO3- + H+
OxyHb donates O2 and K+, binds H+
HCO3- represents the alkaline reserve
In the lungs pO2 is high and pCO2 is low
Hb binds O2 and K+, releases H+
HCO3- + H+ -> H2CO3 -> H2O + CO2 (exhaled)
Bohr effect
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The parameters of acid-base balance
Blood gas analyzer (Astrup method)
Arterial blood sample (radial, femoral artery)
Parameters: pH, pCO2, pO2, HCO3-, BB (bufferbase),BE (base excess),AG (anion gap), pot. HCO3
-
BB = 24 mmol/l HCO3- + 8 mmol/l Hb- + 15
mmol/l protein- + 1 mmol/l HPO42- = 48 mmol/l BE = BBpatient - BBnormal ~ 0 (-2/+2 mmol/l)
AG = ([Na+] + [K+])([Cl-] + [HCO3-])< 15 mmol/l
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Acid-base imbalances
Respiratory acidosis: pCO2, +/-pH
lung diseases, inhibition of the respiratory center
Respiratory alkalosis: pCO2, +/-pH hyperventillation, overstimulation of respiratory center
Metabolic acidosis: HCO3- , +/-pH Ketoacidosis,
lactic acidosis, diarrhea, pathology of the kidneys
Bikarbonate dose = BE x 0,3 x kgbodyweight Metabolic alkalosis: HCO3
- , +/-pH
can be iatrogenous, after prolonged vomiting
Compensation: at the level of the kidneys and lungs
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Mineral metabolism and pH
relationship In extrarenal cells the protons move in the opposite
direction compared to potassium ions (eg. in metabolicacidosis many protons from the extracellular space try to
get into the cells, while potassium ions exit theintracellular compartment
At renal level there is a competition between theexcretion of these ions (in metabolic acidosis more
protons are eliminated by urine and less potassium)
Insulin promotes the entrance of potassium into cells, inthe treatment of diabetic ketoacidosis KCladministration is required
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I. Case presentation
Male patient, 42 years old. He suffered a caraccident, and is transported to the hospital with
severe chest pain. The x-ray showed multiple ribfracture.
Laboratory results:
HCO3-: 30 mmol/l (normal 2428 mmol/l)
pCO2: 65 Hgmm (normal 30 - 46 Hgmm)
BB: 48 mmol/l (normal 4448 mmol/l)
pH: 7,25 (normal 7,357,45)
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What kind of acid-base imbalance is?
A. Compensated respiratory alkalosis
B. Decompensated metabolic acidosis
C. Compensated metabolic alkalosis
D. Decompenated respiratory alkalosis E. Decompensated respiratory acidosis
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What is the cause of the imbalance?
A. Overstimulated lung function due to thetraumatic injury of the respiratory center
B. Circulatory failure with the subsequentaccumulation of organic acids
C. Prolonged starvation leading to
accumulation of ketones in the body D. Poor lung function due to the chest trauma
E. Hyperventilation due to a panic attach
caused by the car accident
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What can be the cause of the slight
increase in the bicarbonate level? A. Bicarbonate secretion in the liver in case of
alkalosis
B. It is due to the compensatory activity of thekidneys
C. The kidneys retain more protons to
counteract the alkalosis of the patient D. Bicarbonate is produced in the kidneys tocounteract acidosis E. It is increased in order toeliminate the non-volatile carbonic acid
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II. Case presentation
Female patient, 18 years old, 50 kg body weight.
Personal pathological background: The patient isknown with type 1 diabetes mellitus diagnosed 4
months ago. Case history: Presenting a urinary infection, the patient
gives up (wrong decision!!!) the insulin treatment; shelives through a very stressful period (graduation). She
is found in a comatous state by the paramedics. Clinical examination: Unconscious patient, with dry
skin, acetone-like breath, blood pressure = 80/50(normal 120/60 for her age).
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Laboratory analyses
- Glycaemia: 580 mg/dl [normal: 60-100 mg/dl]
- Blood gas analyzer:
pH = 6,98 [normal: 7,35-7,45]
pCO2 = 28 Hgmm [normal: 30-40 Hgmm]
BB (buffer base) = 36 mmol/l [normal: 46 (44-48) mmol/l]
HCO3- (bicarbonate) = 12 mmol/l [normal: 26 (22-28) mmol/l]
BE (base excess) = . . . . mmol/l [normal: -2 - +2 mmol/l]
AG (anion gap) = . . . . mmol/l [normal: 10-18 mmol/l]
- Ionogram: Na+: 150 mmol/l [normal: 135-145 mmol/l]
K+: 6 mmol/l [normal: 3,6-4,8 mmol/l]
Cl-: 115 mmol/l [normal: 97-108 mmol/l]
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Questions
What is the cause of the metabolic imbalance in
case of this patient?
Calculate the base excess (BE): . . . . . . . . . .
BE (mmol/l) = BB actual - BB normal
Calculate the anion gap (AG): . . . . . . .
LA (mmol/l) = (Na+ + K+) - (HCO3- + Cl-)
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What kind of acid-base imbalance is
present in case of this patient:
A. Decompensated respiratory acidosis B. Decompensated metabolic alkalosis
C. Decompensated metabolic acidosis
D. Compensated metabolic alkalosis
E. Compensated metabolic acidosis
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Does the AG confirm or not the
diagnosed imbalance of the acid-
base equilibrium?
A. Yes, because a value over 15 mmol/l of the
AG is due to the increase of non-volatile acids(ketone bodies in our case)
B. Yes, because the value exceeds 1 mmol/l,
which is pathologic C. No, because in metabolic acidosis the AG
is negative
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How can you explain the slightly
decreased pCO2 in case of this patient?
A. It is due to the respiratory alkalosis B. The respiratory compensation of metabolic
acidosis causes this value
C. It is a consequence of the respiratoryacidosis due to the loss of consciousness
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The treatment of the patient will
be done with:
A. 10% glucose, sodium bicarbonate (500
mmol/l) B. 0.9% NaCl (1 liter/h), insulin (10 UI/h),
sodium bicarbonate (50-75 mmol/l), KCl
(1g/l)
C. Insulin (100 UI/hour), 10 % glucose
D. 0.9% NaCl, insulin (1 UI/hour), sodium
bicarbonate (5 mmol/l)
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III. Case presentation
Female patient, 68 years old, retired.
Case history: Hypertension for 10 years, 2 years ago she had anepisode of acute lung edema. Her prescribed treatment is: Digoxin(digitalis alkaloid, improves the contractile force of the
myocardium, decreases the pulse), Aspacardin (contains Mg andK), Furosemid (loop diuretic, increases the salt elimination by theurine), Isosorbide dinitrat (vasodilator), Captopril (ACEinhibitor, antihypertensive drug, helps the pump function of themyocardium, decreases the aldosteron secretion). Due to lack ofmoney, she cannot affor to buy all the medication, this month she
took only Digoxin, Furosemid and Captopril. Symptoms: Muscle weakness, constipation, apathia, palpitations.
Examination: Pale skin and mucosa, low muscle tone, pulse: . . . .. . . .[normal: 60 - 100 beats/minute]
Laboratory results: Serum K: . . . . . . . . [normal: 3,6-4,8 mmol/l]
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Diagnosis
Which is the most probable diagnosis for thispatient:
A. Addisons disease (corticosuprarenaldeficiency)
B. Cushings disease (corticosuprarenalhyperfunction)
C. Renal insufficiency D. Left heart failure
E. Acute myocardial infarction
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Pulse, potassium
Which values of the pulse do you expect to have at
this patient:
a). 50-60 beats/minute c). 110-120 beats/minute b). 70-80 beats/minute
Which values of the serum potassium do you
expect to have at this patient :
a). 6,5 mmol/l c). 3,3 mmol/l
b). 4,2 mmol/l
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Note
Addison's disease is characterized by hyperpigmentationon the palms, feet and mouth, weight loss, dehydration,adinamia, hypotension, muscle weakness, apathy. Themost common cause of adrenal insufficiency is based
autoimmune mechanism, rarely it is caused by infection(tuberculosis), stroke, tumor metastasis.
Pulmonary edema is a sign of decompensated left heartfailure.
Acute myocardial infarction is characterized by violentchest pain, sweating, agitation, dyspnea.
In acute renal failure serum potassium, serum creatinineand urea levels are increased due to poor elimination in
the urine.
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Biochemical and immunological
analyses
Practical applications
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Modern laboratory diagnostic tests
Laboratory tests used in the diagnosis of autoimmun
diseases
Immune markers of digestive tract Hereditary thrombophilia profile
Diagnosis of hematological diseases (anemia)
Immune markers of chronic infections Tests in pregnancy: TORCH, double and triple test
Tumor markers
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Laboratory diagnosis in autoimmune
diseases
Autoimmune diseases: rheumatoid polyarthritis,
systemic lupus erythematosus, systemic sclerodermia,autoimmune arthritis, Crohn's disease, colitis ulcerosa
The type 1 diabetes has also autoimmune mechanism,
the beta pancreatic cells are affected
Autoimmune diseases have complex forms of
expression, these patients usually need long-term drug
treatment, the target is not to cure but to relieve
symptoms and lengthening periods of remission.
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Diabetes mellitus and biliary
cirrhosis Diabetes mellitus: antibodies against islet cells, insulin,
glutamate decarboxylase, tyrosin phosphatase
C peptide level shows the endogenous insulin secretion Primary biliary cirrhosis: antimitochondrial antibodies
(AMA) are present, in over 90% of the cases. They can
occur also in other liver diseases (ex. chronic hepatitis),
in autoimmune diseases (lupus, rheumatoidpolyarthritis) or endocrine pathology (Addison disease,
disorders of the tyroid gland)
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Cyclic citrullinated peptide
Rheumatoid factor has recently been used in the
diagnosis of rheumatoid polyarthritis, but it has
low specificity, and it is negative in seronegativepatients; CCP-antibodies: specificity >95%,
sensibility 80%
CCP is produced in the inflamed synovialmembrane, the plasma cells produce antibodies
against CCP, which is a reliable marker for
rheumatoid polyarthritis
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Immune markers
Antinuclear antibodies: are antibodies that react withantigens in the nucleus
ANA Screening: SLE, sclerodermia, mixed connectivetissue disease, Sjgren's syndrome, polymyositis /
dermatomyositis Anti-histone antibodies appear in the drug-induced
lupus in 95% of the patients, it is a main diagnosticcriteria
Native DNA antibodies appear in 60% of the patientssuffering from lupus, it is a diagnostic criteria, used inthe monitoring, indicates severity especially innephritis, it participates in the formation of CIC, which
are deposited in the organs
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Immune markers
Anti-Sm antibodies are formed against small
ribonucleoproteins, they are specific markers of
lupus, incidence 20-30% Anti-U1-RNP antibodies are formed against the
U1 type small ribonucleoproteins, they are
essential markers of the mixed collagen disease,in lupus indicates favorable evolution, with less
frequent kidney involvement
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Immune markers
ANCA: these are antibodies against the antigens in
the cytoplasm of neutrofil granulocytes
Subtypes: c-ANCAWegener disease, systemicvasculitis, glomerulonefritis
p-ANCAidiopatic glomerulonephritis,
polyangeitis
x-ANCAautoimmune hepatitis, Crohn
disease, colitis ulcerosa)
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Lupic anticoagulant
LA: are antibodies directed againstphospholipid-proteincomplexes. They interfere with the in vitro phospholipid-dependent coagulation tests, making APTT longer
In vivo, their presence shows a high risk for thrombosis(thrombophilia). In patients with positive value 24-36% is theincidence of thrombosis (deep venous thrombosis, pulmonaryembolism)
Two positive results in 12 weeks mean antiphospholipid syndrome.
In women with spontaneous abortions 10% are generally positive forLA
LA is usually present in autoimmune diseases, but it can be presentin viral infections, drugs can cause it (hydralazine, clorpromazin,streptomycin, chinidin)
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Antiphospholipid syndrome
It is an autoimmune diseases, anti-phospholipid antibodies
are present, arterial or venous thrombosis occurs and
repeated abortions. It maybe a separate disease, or may be associated with
other autoimmune diseases (SLE, 50%). It is included in
the diagnostic criteria of SLE. Phospholipid antibodies
(IgG, IgM) appear also in other autoimmune diseases,infections (ex. sifilis, HIV), after administration of certain
drugs, 5% in healthy patients.
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Thrombohilia profile
The arterial and venous thrombosis and embolismis the leading cause of morbidity and mortality indeveloped countries. Excessive activation of
coagulation, or the inhibition of the anticoagulantmechanisms can lead to thrombosis.
Trombophilia: can be hereditary or induced
Hereditary: pathologic clotting fators (ATIII , Cprotein, S protein, thrombomodulin, protrombin,fibrinogen), plasminogen deficiency, elevatedhomocystein level.
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Gluten enteropathy
Screening and monitorization: IgG againstgliadine andanti-transglutaminase antibodies (non invasive)
Anti-endomysium IgA antibody levels show a good
correlation with the severity of the disease, its leveldecreases in gluten-free diet. After 9 months of diet it
becomes negative (specificity 97-100%, 85-98%sensibility).
It is better to perform the dosage for both auto-antibodies(anti-endomysium and anti-transglutaminase)
Dg. Biopsy of the intestinal mucosa shows atrophy.
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Risk factors for hepatitis C - questionnaire
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Hematology: anemia
Transferrin (Fe transporter protein) and
ferritin (binds Fe in the deposits) help
the early diagnosis of iron deficiencyanemia, it has to be diferentiated from
the low iron level in malignancies and
in chronic diseases (iron deposited in
the macrophages is increased).
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Laboratory tests in pregnancy
TORCH: Toxoplasma, Rubeola, Cytomegalovirusand Herpes IgG and IgM antibodies
Double test: PAPP-A, free beta-HCG, ultrasoundscan (craniocaudal length, nucal translucence) and
personal data (smoking, diabetes, type offertilization, body weight, etc.) for the diagnosis ofDowns disease (21 trisomy) and 18 trisomy duringthe 11th-13th weeks of pregnancy (I. trimester).
Triple test: AFP, free estriol s HCG, it is doneduring the 14th-19th weeks of pregnancy, forDowns disease and neurological tube defects (II.t.).
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Tumor markers - classification
- oncofetal and oncoplacentar antigens ex. CEA, AFP, hCG;
- carbohydrate molecules which contain epitopes
recognized by monoclonal antibodies CA 19-9, CA 125, CA
15-3;- differantiation and proliferation antigens ex. NSE, PSA,
beta2-microglobulin;
- ectopic hormones ACTH is produced in lung cancer,
calcitonin in thyroid cancer
- ectopic proteins: monoclonal immunoglobulines and
proteins: BenceJones proteins in multiple myeloma
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The role of tumor markers
-Early diagnosis of malignant tumors in thehighr risk patinentsAFP in hepatic cirrhosis,AFP and HCG in case of germinative tumors,
PSA >50 years males for prostate adenoma,calcitonin in thyroid gland tumors;- Monitoring: before the first therapy session, tohave a baseline. Some of them have prognostic
value, their decrease after the treatment help us toevaluate the mass of ther residual tissue, theirincrease can reveal the reactivation of the disease
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Melanoma
Breast cancer