Mineral, pH, Immunological Markers Plus Case

7/27/2019 Mineral, pH, Immunological Markers Plus Case

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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

Mineral, pH, Immunological Markers Plus Case

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