1. Etiology of disease – external and internal etiological factors.

Health is social, economical, psychological wellbeing not just the absence of

disease. Etiological factor is considered every factor that can disturb the balance
between organism and its surrounding. By origin they can be divided in internal
and external while by role in primary and secondary.

EXTERNAL etiological factor is every factor that is located outside our organism
and when it penetrates inside it can provoke damage. Here belong: BIOLOGICAL,
CHEMICAL, PHYSICAL AND OTHERS.

Biological: all sorts of microorganisms that provoke damage when they penetrate
in our organism like bacteria, fungi, viruses, etc.

Chemical: every chemical when dosed that provokes damage by chemical

mechanisms (intoxications)

Physical: all strong forces located outside our organism like heavy mechanical
load, extreme temperatures, pressure etc.

In other etiological factors food intake is one of the most important since is needed
for adequate energy balance and function of organism. Also low food intake
provokes some disease by itself (vitamin deficiencies)

Every mechanism that usually serves to protect our organism when damaged can
be considered as INTERNAL etiological factor. From non-specific mechanisms we
have anatomical barriers like skin which when is damaged can be an open door for
bacteria penetration. By specific protective mechanisms that protect our body we
consider humoral and cellular immunity which when damaged can’t defend our
body in a proper manner. Genetical traits are also considered as internal etiological
factor (mutations) which lead to desease.

2. Primary and secondary etiological factors

Some diseases are caused by only one factor and if that factor is strong enough
there is no need for others (Electricity of high voltage will kill a man by itself).
However, some diseases need cooperation of more factors in order to develop
certain disease. In this case the main factor which causes disease is called primary
etiological factor while others who help the development are called secondary
etiological factors. For example in tuberculosis the main etiological factor is Kohl
bacillus and secondary is sensitivity of organism, malnutrition or decreased
immunity.

In hereditary diseases which are monogenic there is no need for secondary

etiological factor (Down syndrome, hemophilia, Edwards etc) while in polygenic
genetic disorders like diabetes mellitus for example secondary factors like food
intake rich in carbohydrates is needed.

In some diseases we don’t know what is the primary etiological factor that causes
disease and these are called IDIOPATHIC diseases. Only thing that we know is
secondary etiological factors which help the disease to develop and in this case
they are called factors of risk. For example atherosclerosis is an idiopathic disease
with unknown primary factor but we know the factor of risk for its development –
increased LDL, smoking, etc.

3. Mechanism of inflammatory reaction and role of mediators.

Inflammation is a universal response of tissue to damage. When inflammation
occurs mediators are released which control all processes of inflammation. They
can be classified in several groups: VASOCATIVE AMINS, PROTEIN
SYSTEMS OF PLASMA, METABOLITES OF ARACHIDONIC ACID,
CYTOKINES & OTHER

Vasoactive amins are compounds that are synthesized and stored in cells. These
compounds are released during inflammatory process and they have vasodilatory
effect. HISTAMINE is produced and stored in mastocytes (connective tissue) and
released in acute phase of inflammation. SEROTONIN belongs also to this group
and it’s made out of tryptophan. For its transport platelets are needed and when
they aggregate it gets released.

Protein systems of plasma: coagulation, complements and kinin system which

represent a chain reaction that serves to stop the bleeding, remove microorganism
and localize the injury. Kinine is an active polypeptide formed from proteins of
plasma that dilates blood vessels and provokes pain.

Metabolites of arachidonic acid represent hormones of low range activity that are
synthesized and removed fast from our body. (PROSTAGLANDIN,
LEUCOTRIENE)

Cytokines are compounds that serve for intercellular communication. The most
important from this group are INTERLEUKINS. They can act on the cell where
they are secreted, nearby cells or cells that are located far away. Interleukins act on
release of cortisol, stimulate release of white blood cells from bone narrow, act on
thermoregulative centre in hypothalamus, liver, etc.

Others are growth factors that are needed for differentiation and proliferation of
cells. Tumor necrosis factor (TNF) is delaying multiplication of granulocytes and
monocytes. Thrombocyte growth factor (TGF) is needed for synthesis of cells that
take action in inflammation.

4. Changes in host during inflammation

During inflammation changes in our body occur in range of biological-biochemical
syndrome of inflammation. Connection between local damage and BBSI is
achieved by interleukins. In acute response of inflammation phagocytosis is
activated and mediators are released that act on long distance tissues and organs.
Interleukin 1 acts on thermoregulative centre of hypothalamus and provokes
increased body temperature which is a basic sign of inflammation. Also it
stimulates granulocytopoesis in bone narrow. Interleukine 6 is acting on liver and
stimulates synthesis of CRP (C reactive protein) which represents protein of acute
phase of inflammation. Acute inflammation has the role to stop progression of
inflammation, localize the injury, remove cause and repair eventual damage. If
mechanisms which control this fail then the inflammation is passing in chronic
state which is not productive and provokes more damage.
 5. Primary (congenital) immunodeficiency
Deficit or defect of one component in immune system can cause disease and that is
called immunodeficiency. They can be primary (congenital) and secondary
(acquired).

Primary immunodeficinecies are caused by genetic disorder and they can be

classified in: ID caused by disorder in B lymphocytes, ID caused by disorder in T
lymphocytes, combined and other.

ID caused by disorder in B lymphocytes provoke loss in humoral immunity. Defect

can be on level of B lymphocyte maturation or response of a grown lymphocyte.

*Bruton syndrome is characterized by stop in B lymphocytes maturation. It’s seen

mostly in male kids with low Ig in serum, low or absent B in blood and no
plasmocytes in bone narrow.

*Neonatal hypogamaglobulinemy: low concentrations of Ig in first 3-7 months

after birth which is normal. It vanishes by itself.

ID caused by disorder in T lymphocytes provoke lack in cellular immunity. It can

occur also due to defect in maturation or response.

*Thymus hyperplasia causes disorder in maturation of T lymphocytes.

*Nezelof syndrome is a disorder with abnormal shape of thymus with infections

due to lymphopenia

*Cellular immunodeficiency due to lack of PNP (Purine nucleoside phosphatase).

This enzyme is needed to convert guanosine to guanine. Since there is no enyme
deoxyguanosine is accumulated which has a toxic effect on T lymphocyte

Combined: lack in cellular and humoral immunity. Kids suffer from very severe
infections after birth.

Other: Immunodeficiency by deficit in complement system or phagocyte cells.

Most known disease is chronic granulomatous disease that is characterized by
chronic purulent infections.
 6. Secondary (acquired) immunodeficiency
It represents a group of disorders in immunocompetent patients.
Immunocompetence means that a person has lower resistance to infections and it
can occur due to malnutrition, dissemination of malignant process, HIV infection
and others.

AIDS (acquired immunodeficiency syndrome): This is a high lethal, epidemic

disorder caused by HIV infection. HIV virus is sexually transmitted and it affects
CD4 and CD8 lymphocytes. Virus causes direct damage in them and by infiltration
in thymus it stops their maturation in thymus so persons suffer from lack in cellular
immunity. Patients usually get B cell lymphoma or Kaposhi sarcoma and get
infected often by candida albicans, toxoplasma gondii and viral hepatitis.

Secondary immunodeficiencies are seen also in other disorders. In leukemia

malignant cells infiltrate bone narrow and thymus so immunity is damaged. In
cases of radiation lymphocytes are destroyed because they are sensitive to it.

7. Mechanism of autoimmune disease

Main characteristic of our immune system is that it can attack foreign antigens but
not its own. This is called autotolerance. If somehow mechanisms that control
autotolerance fail then immune system will attack its own antigens and this is
called autoimmunity. There are many hypothesis how autoimmune disorders occur.

Molecular mimicry: Structure of antigen from foreign microorganisms is similar to

structure of antigen in our immune system. In rheumatoid fever connective tissue
antigen is similar to streptococcal antigen.

Changes in determinants by random mutations can change our antigen hence

special antibodies are formed so it’s destroyed.

Anatomical barrier: Periphery antigens usually don’t come in contact with T

lymphocytes. If contact occurs they are recognized as foreign and damage will
occur.
Ignorance of autoantigen: Usually antigens in our body are not presenting
themselves to T lymphocyte so there is no reaction. But if autoantigen presents
itself somehow then T lymphocyte will attack.

Policlonic activation: Potentially autoreactive T and B lymphocytes are not

removed by process of deletion and they can be triggered by many factors.

*Big role in these mechanisms have also infections. When person is infected local
response activates ANTIGEN PRESENTING CELL production which can activate
autoreactive lymphocytes. There is also a correlation to genetical predisposition for
autoimmune diseases (family history)

8. Immunopathogenic mechanisms in autoimmune diseases.

Mechanism of tissue damage in autoimmune diseases can be divided in processes
mediated by antibody and by cells. Antibody can have a role in pathogenesis by
inactivation or stimulation of receptors, formation of immune complex or
cytotoxicity. Cells can damage tissue by cytokines formation or cytotoxicity.

Depending on parts that these mechanisms affect they can be organ specific and
systemic.

In organ specific antibodies are produced for antigen that is located in one specific
organ. for example in Hashimoto thyreoiditis antibodies are produced for antigen
in thyroid gland which leads to lesion formation.

Systemic lupus is an example of systemic disease where antibodies are found in

many organs and by their effectory mechanism activation they provoke damage in
many organs. In this case the organs are: kidneys, joints, skin, blood vessels, cns.
This is considered as a hyperreactivity of humoral immunity.

9. Type I hypersensitivity reaction

This reaction is caused by extreme release of mediators from mastocytes
(histamine) in sensibilized persons and it’s mediated by IgE antibodies. When
person first comes in contact with specific antigen (allergen) IgE antibodies are
produced. IgE surround mastocytes in connective tissue and this process is called
sensibilization and it lasts up to 14 days. When person comes in contact with same
allergen after sensibilization is done then degranulation of mastocytes will occur
and hence mediators will be released which act on smooth musculature and blood
vessels.
Allergens like pollen and dust can act on eyes and provoke conjunctivitis. If they
are also inhaled in upper respiratory airways they can cause allergic rhinitis while
in lower allergic bronchitis.

Allergens that are swallowed which are mostly found in strawberries or milk will
cause vomiting or diarrhea.

Most severe type of this reaction in anaphylactic shock that occurs due to massive
degranulation of mastocytes due to systemic presence of antigen. It’s characterized
by extreme vasodilation that results in low blood pressure. Since blood flow is
slowed down transudation occurs and edema is seen (mostly in larynx). With some
general symptoms like nausea, vomiting, eventual loss of continence.

10. Type 2 hypersensitivity reaction

This type of reaction is mediated by IgG and IgM antibodies which when bound to
antigen provoke damage or death of cells. Damage can occur due to phagocytosis,
cellular lysis or cytotoxicity dependant on antibodies.

By this type of reaction occur: Post transfusional reaction, hemolytic anemia,

hemolytic fetal disease, rejection of foreign bodies and God Pascher syndrome.

Post trasnsfusion reaction: Due to transfusion of blood that is not in adequate ABO
group. Antibodies bind to blood antigen and cause red cell aggregation or lysis.

Hemolitic fetal disease: When mother who is Rh+ carries a Rh- fetus. During
delivery mothers blood can come in contact with fetus blood hence she will be
sensibilized. During next pregnancy if fetus is Rh-, IgG can pass placenta and
cause erythrocyte lysis.
Hemolitic anemia: antibodies in autoimmunity bind to antigens of erythrocytes and
platelets.

God Pascher: Autoreactive antibodies bind to basal membrane of capillaries in

lungs and kidneys and provoke damage.

11. Type 3 hypersensitivity reactions

This type of reaction is mediated by IgG and IgM which bind to antigen and form
immunocomplex that are sedimented themselves and activate complement system
and phagocytosis. This type of reaction can be general and local. If there is more
antigen present then it will be general, if more antibody then local.

Local reaction is also called reaction by Arthus. After application of antigen

complex between antigen and IgG is formed which activates complement system
and inflammation occurs. This occurs in farmer lung disease, pigeon keeper
disease.

General is seen when sensibilized person receives a big amount of antigen. Classic
example for this is horse serum disease when horse serum was used to cure tetanus.
Immune complexes are flowing thorugh systemic circulation and activate
mediators. Mediators will retract blood vessel walls so immunocomplex can
sediment there and provoke inflammation, body temperature increase, rash, pain in
joints, etc.

12. Type 4 hypersensitivity reaction

This reaction depends on T lymphocyte and by immune response it differs only by
intensity. T lymphocytes can provoke damage cy direct cytotoxicity which lyses
the cell (specific for antigen)

Second way of provoking damage is lymphokines formation that is specific also

for antigen but can act non specifically. This is possible only in persons who are
sensibilized and by next contact with antigen lymphokines are produced.
Lymphokines act on capillaries so they are more permeable – edema can be seen.
Macrophages provoke damage and tissue necrosis can be seen. Classic example for
this is tuberculin probe. When applied to persons that are senisibilized redness will
be seen on puncture spot. It will get hard also due to fibrin infiltration. After
several days tissue necrosis can be seen.

This reaction can also be general when there is excess antigen so symptoms as
fever, joint pain, headache, nausea etc. can be seen.

13. Hereditary diseases by chromosomes

Normal human genome has 46 chromosomes. 22 pairs are autosomal and one pair
are sex chromosomes. For males sex chromosomes are XY while in females XY.
Chromosomes are arranged in 7 groups A-G and they are arranged by size.
Most severe disorders in chromosomes are seen when there is one chromosome
more o one chromosome less. This is called aneuploidy and it can come in 2 forms.
Trisomy when there is excess of chromosomes and monosomy when there is 1
chromosome less. These chromosomal aberrations occur in meiosis when
chromosomes are split from 46 to 23. If anything goes wrong, one gamete will
have 22 and other will have 24 chromosomes. If aberration happens on big
chromosome organism can’t develop but if it is on smaller ones then it develops
with certain consequences.

Monosomy: Turner syndrome 45,xo. Individual is female, there is no follicles in

ovaries so it suffers from infertility, and lack of secondary sexual characteristics
with normal mental development.

Trisomy: Down syndrome, 47xx aberration on 21st pair. Imediately after birth we
can see wide openings between eyelids, short fingers, macroglossia, flat nose etc.
Individuals develop with mental retardation.
Edwards syndrome, 47xx aberation on 18th pair. Children suffer from severe
consequences and die usually soon after birth.
Klinefelter syndrome, 47xxy aberration on sex chromosome. Individual is
obviously male due to Y chromosome but it has strongly expressed female
characteristics. Normal mental development, infertility, female voice,
gynecomastia.

In structural chromosome aberrations only one part of chromosome is changed or

missing. This can occur due to processes of deletion or translocation.
Consequences are not lethal but physical and mental retardation is seen.

14. Hereditary disorders caused by gene mutation

Mutations occur spontaneously in process of DNA replication. Beside spontaneous
they can be induced by many factors like radiation for example. If enzymes don’t
repair DNA mutation then it gets transmitted to other generations.

By length of DNA that is affected they can be DOT (one base or more) and
POLYGENIC mutations.

DOT: Chromosome that is affected is not morphologically changed so in order to

diagnose it advanced DNA technologies must be used. If structural gene is affected
then protein that is synthesized out of it will have a different structure hence
different biochemical function. If regulating gene is affected then speed of
synthesis affected. Lower speed of synthesis is more common where protein levels
are decreased or missing totally. If enzymes are low synthesized then metabolism
slows down due to low enzymatic activity. Clinical manifestations of these
mutations are morphological defects, metabolic disorders, decreased immunity,
lack of some organ functions, etc.

POLYGENIC: More genes are affected and disease will manifest itself only by
action of other etiological factors. Diseases that belong to this gropu for example
are coronary heart insufficiency, diabetes, infertility etc.

15. Autosomal dominant and recessive disorders

These are disorders located on autosomal chromosomes. In dominant type if only
one of 2 homologous genes is affected the disease will manifest itself. so these are
visible in heterozygotic states. Sometimes there is a autosomal disorder but person
is clinically healthy.

If one sick person has kids with healthy person – 50% sick

If 2 sick persons have kids – 75% sick

In recessive type both allele genes must be affected in order for disease to manifest
itself. If only one allele gene is affected and other one is healthy then that person is
considered as an conductor (carrier of disease)

If one sick person has kids with one healthy person – all conductors

If conductor has kids with healthy – 25% conductor, rest healthy

If 2 conductors have kids – 25% healthy, 25% sick, 50% conductors

16. Disorders of sex chromosomes

These disorders can be recessive or dominant. Dominant type is not so common
but we can say that males are diseased and that females are conductors. In
dominant type pathological gene is located on X chromosome and disease will
manifest itself also in females. If father is sick then all male kids are healthy (Y
from father, no X). If mother is sick then all kids are sick.

Recessive is the most common again with pathological gene located on X

chromosome. In females there is another X chromosome so the disease will not
manifest itself but they will be conductors. In males there is only one X
chromosome so they will be diseased.

If father is healthy and mother is conductor – 25% sick *males, 75% healthy (25%
carrier)

If father is diseased and mother is healthy – males are healthy, females are cariers

Only if male is diseased and female is a conductor – there is a possibility that

homozygote female can be diseased.
Diseases that are transmitted in this manner are: hemophilia, color blindness,
muscle dystrophy.

17. Disturbances in total protein and albumin in serum

In normal metabolism proteins are found in concentration from 60-80g/l. Disorders
can go in range of hypoproteinemia and hypoproteinemia. Both of them can be
absolute and relative.

HYPERPROTEINEMIA

Absolute is seen in immunoglobulins when there is some chronic immune disease

present like systemic lupus erythrematosus. In relative there is no change in actual
concentration but amount of water decreased (dehydration)

HYPOPROTEINEMIA

Relative hyperproteinemia is seen when concentration of water increases with

protein content unchanged.

Absolute can occur due to increased loss of proteins, low synthesis or increased
catabolism. Low synthesis is seen when there is no enough amino acids for their
formation (low protein intake, maldigestion, malabsorption). Increased catabolism
is seen in hormonal problems where hormones that have catabolic effects are
increased. Loss of protein can occur via urine, stool or burns. If loss via urine is
greater than 5g/l then that state is considered as a nephritic syndrome. Via stool
(exudative enteropathy) persons can lose up to 40% of protein amount while
healthy lose 1% only. When burns occur persons can lose up to 30g of protein per
hour.

ALBUMIN

Albumin represents half amount of total proteins. Disorders with abnormalities in

albumin synthesis are analbuminemy and bisalbuminemy. In bisalbuminemy there
are two types of albumins and this is not correlated to pathologies. In
analbuminemy there is low synthesis and edema can be seen.

Higher concentrations can be seen in states of dehydration

Lower concentrations occur due to low synthesis, increased dissolution or loss. For
doctors concentrations under 35g/l should take interest and if that concentration
drops under 20g/l then edema is seen. (Has oncotic activity)

18. Disturbances with decrease of globulin fraction

Precise information about protein metabolism can be obtained by electrophoresis
of proteins where we get 5 fractions: albumin, alpha 1 globulins, alpha 2 globulins,
beta globulins and gamma globulins.

Hypoalphaglobulinemia is not so common but it occurs usually due to loss of

antitripsine, ceruloplasmine or haptoglobine. Antitripsine neutralizes lysosomal
elastase so if there is lack in its concentrations damage of blood vessels can occur.
Ceruloplasmine is needed to transport copper in a non toxic form and haptoglobine
reduces loss of hemoglobin via urine.

Low beta fractions are usually related to hypolipoproteinemias. Transferine also

belongs to this class (binds Fe) so low beta fraction can also indicate anemia.

Hypogamaglobulinemia: It’s always associated with immune disorders since this

fraction contains immunoglobulins and hence frequent infections are seen. It can
be primary and secondary. In primary type plasmocytes synthesize low amount of
them due to genetic disorder. In secondary they are low due to some disease that
can influence their low synthesis, degradation or loss.

19. Disturbances with increased globulin fractions

These disturbances are seen in practice since protein concentrations tend to
increase during inflammations.

Hyperalphaglobulinemia is seen in acute states of inflammation, after surgery,

rheumatic fever, tumors, nephritic syndrome.

Hyperbetaglobulinema is seen in states where lipoproteins are increased and in

nephritic syndrome. In this fraction we have transport proteins and tumor markers.
Hypergammaglobulinemia is very important because this fraction is made of
immunoglobulins so we can determine states where immunoglobulins are produced
in excess. These disorders can be influence more classes of immunoglobulins or
only one. (poly/monoclonic)

Polyclonic: All Ig classes increase due to chronic inflammation, vaccination,

infection etc. By order first IgM increase (7-10days) then IgG (after 14dayss. Some
diseases give rise to certain classes of immunoglobulins. Increased IgG is seen in
chronic hepatitis or systemic lupus. IgA rises in inflammations of digestive and
respiratory tract. IgM in bile cirrhosis and hepatitis.

In monoclonic disease plasmocytes that are pathologically changed synthesize one

pathologically changed class that is called paraprotein. Increased paraproteins are
seen in multiple myeloma, Waldenstrom (lymphoplasmocitic lymphoma), heavy
chain disease.

20. Disorders in plasma fibrinogen concentration

Fibrinogen is a globulin whose concentration in plasma goes from 2-5g/l and
disorders can go in range of hyper and hypofibrinogenemy.

Decreased concentrations can be primary and secondary. In primary the cause is

always low synthesis and we have 2 disorders: congenital afibrinogenemy and
hypofibrinogenemy. In afibrinogenemy there is total lack of fibrinogen, clinically
its manifested as hemophilia. Bleeding can be seen when cutting umbilical cord in
neonates hence it can be lethal. In hypofibrinogenemy concentrations of fibrinogen
are from 0.2-1g/l and its not so severe as afibrinogenemy.

Secondary hypofibrinogenemy can occur due to low synthesis or fast usage of

fibrinogen. Low synthesis is seen only in states where whole liver parenchyma is
damaged like terminal stages of liver cirrhosis. Fast usage is seen in disseminated
intravascular coagulaton where big amount of thromboplastine goes in blood and
activates coagulation with usage of fibrinogen (pregnancy complication) or in
increased fibrinolytic activity where fibrinogen is dissolved by plasmine and fibrin
(metastasis of prostate cancer).
Hyperfiibrinogenemy is seen in all inflammations since mediators like interleukine
are stimulating its production in liver. Fibrinogen has great diagnostical value for
laboratory. When concentrations of fibrinogen go back to normal it means that
inflammation stopped.

21. Etiology, pathogenesis and stages of diabetes mellitus

development
Degradation of glucose to water and carbon dioxide presents a central metabolic
pathway for every cell. This pathway can go towards producing energy deposits in
forms of tryglicerides, glucagon or proteins and towards usage of these energy
deposits in states like starvation.

Glucose is usually found in our blood in concentrations from 4.2-6.1mmol/l.

Homeostasis of this concentration is obtained by many mechanisms. Increased
concentrations (hyperglycemia) is prevented by insulin while lower concentrations
by cortisol, glucagon, ACTH, TSH, adrenaline hence hypoglycemia is better
supported and there is bigger risk for hyperglycemic state to happen.

Hyperglycemia is a main disorder of glucose homeostasis that has 3 stages. Fasting

(ogtt – not more than 7.8 mmol/l), postprandial (ogtt – 7.8-11.0 mmol/l) and
diabetes mellitus (ogtt bigger than 11.0 mmol/l)

Diabetes is classified in 4 groups: type 1, type 2, gestational and secondary that

follows other diseases.

TYPE 1: Complete lack of insulin due to autoimmune disorder that is destroying

pancreatic B cells that produce it. It’s characterized by early manifestation before
30 years of life, sudden symptoms, application of insulin throughout life. In
formation of this type of diabetes several moments are important:

1st – specific genetic constitution (HLA antigen)

2nd – autoimmune process beginning triggered by unknown factor

3rd – Destruction of B cells in stages

4th – Application of insulin is making the rest of healthy B cells to decrease their
synthesis of insulin but in time they will be destroyed by autoimmune process
(honeymoon phase)

TYPE 2: Seen in people with genetic predisposition and unhealthy lifestyle. These
persons have increased insulin resistance so B cells are working more than usually.
By time these cells are exhausted so person transfers from hyperinsulinic state to
hypoinsulinic state so hyperglycemia occurs. This type of diabetes usually
develops for 12 years, hits 5% of population and can lead to atherosclerosis.

SECONDARY is seen in other diseases due to endocrinopathies where antagonists

of insulin are more secreted (hypercorticism). Also it can be seen due to infection
or usage of some medications (corticosteroids, diuretics)

GESTATIONAL occurs in pregnancy due to increase of insulin antagonists and

vanishes after delivery is done.

22. General pathophysiological disorders in DM

Insulin stimulates entrance of sugar in muscles and fat tissue, stimulates glycolysis,
synthesis of glycogen, proteins etc. Also it inhibits synthesis of glucagon. by lack
of insulin connected pathophysiological changes occur.

1st Due to low stimulation of insulin transporters glucose can’t enter tissues so it
circulates in blood – hyperglycemia

2nd When concentrations of glucose exceed 10 mmol/l it can be seen in urine –

glucosuria

3rd Glucose is osmolary active substance and it binds water – increased amount of
urine

4th Loss of water – dehydration

5th Due to dehydration CNS thirst centre is activated – polydipsia

6th – Since there is no glucose in muscles and energy levels are low we crave for
food
7th There is no energy from glucose so energy is obtained from fat tissue by beta
oxidation

8th Krebs cycle is stopped (not enough AcCoA) so there is no ATP, but ketone
bodies (energy), acetic acid and hydroxybuteric acid is formed in liver.

9th Ketonemia, ketonuria

10th Metabolic acidosis (ketones), and loss of weight by lipolysis regardless that
patient eats a lot.

23. Acute complications of diabetes mellitus

Patients who suffer from diabetes nowadays due to modern therapy can live almost
like completely healthy persons. Acute complications can occur when patients are
exposed to stress since insulin antagonists are secreted and disorders that can occur
are : ketoacidosis, hyperosmolar coma, and lactate acidosis. Also there are some
general symptoms from expressed hyperglycemia like fatigue, increased urination,
increased food intake etc.

Ketoacidosis: Lack of insulin decreases entrance of glucose in tissues so

catabolism of proteins and degradation of fat. By degradation of fat we get ketone
bodies (acid) which provokes metabolic acidosis. For compensation H+ ions go in
the cell while K ions come out the cell so there is extracellular hyperkaliemia.

Hyperosmolar coma: When glucose is excreted via urine it binds water also o there
is dehydration. If somehow there is another dehydration inducer (vomiting,
diuretics) then depression of CNS and coma can occur due to brain dehydration.
There is some insulin circulating in blood so there is no ketosis and degradation of
fat.

Lactate acidosis: pH value of blood drops down and lactates increase over 5
mmol/l . This is seen in insulin lack, liver damage, hypoxia.
 24. Chronic complications in DM
Chronic complications of DM occur due to changes in blood vessels from
increased glucose levels and increased lipoproteins. These complications are called
diabetic angiopathies and can be divided in microangiopathies and
macroangiopathies.

MICROANGIOPATHY: Hyaline material is accumulated between muscle cells in

small arteries. Their wall gets thicker and blood flow is decreased. Polyolic
alternate pathway of glucose metabolism gives sorbitol which has toxic effect on
endothelia and glycosamine pathway gives glycoprotein (sediment). Mostly
affected by these angiopathies are vessels of kidney, retina and vasa vasorum
hence diabetic patients have problems with eyesight, nervous system and kidneys.
Structural changes of blood vessels lead to reduced blood flow in organs hence it
can damage their function.

MACROANGIPATHIES: represents earlier manifestation of atherosclerosis. It

affects coronary, cerebral, limb arteries. This can lead to infarction of organs,
coronary heart disease, cerebrovascular diseases, obstructions etc.

25. Hypoglicemia and consequences

Hypoglycemia is a state where conc. of glucose is under 4.0 mmol/l and symptoms
are always seen when concentrations are under 3.0mmol/l. Hypoglycemia can
occur due to low entrance of glucose in blood (starvation) or due to big amount of
glucose leaving blood due to insulin.

Fasting hypoglycemia: Usually related to starvation or excessive physical activiry.

Also it can occur due to malfunction of glands that secrete insulin antagonists or
due to some tumors of pancreas that secrete insulin all the time.

Postprandial: Related to hypoglycemia after meal and it can be alimentary,

idiopathic or pre-diabetic functional hypoglycemia.

1st Alimentary is seen after stomach resection when meal that is rich in
carbohydrates gives rise in blood sugar levels and insulin is secreted in excess
2nd Pre-diabetic is seen in persons who have genetic predisposition for diabetes
type 2

Other: excessive insulin intake

Hypoglycemia in children: seen after birth whose mothers have diabetes because
they have been surrounded by hyperglycemic blood so insulin apparatus was in
hyperfunction.

Pathogenesis: First group of symptoms occur from CNS due to low energy hence
its decreased activity (decreased focus, irritability, headache, muscle cramps).
Second group of symptoms occur when sympathetic nervous system is stimulated
to compensate hypoglycemia by gluconeogenesis and glycogenolysis (fear, tremor,
cold sweat, tachycardia)

26. Primary hyperlipoproteinemia

Lipids in our body can be endo and egsogeneous by origin. Fatty acids have and
tryglicerides have energetic value while phospholipids and cholesterol have
structural value. Lipids can’t be dissolved in water so they are transported
throughout our body with lipoproteins that represent a complex made of lipids and
protein. These lipoproteins are classified in chylomicrons, VLDL, LDL, IDL and
HDL. Proteins together with lipoproteins are called apolipoproteins and they act as
cellular receptors. Apo 1 is seen in all HDL, Apo 2 in 2/3HDL and Apo B is
structural protein in other classes of lipoproteins.

Hyperlipoproteinemia represents a state where cholesterol and tryglicerides are

increased due to raise in lipoproteins (increased synth, low degradation). They are
classified in primary and secondary. Primary are divided in hyperlipoproteinemia
with increased LDL but normal tryglicerids and hyperlipoproteinemias with both
increased.

LDL increased with normal tryglicerides:

Familiar hypercholesterolemia is autosomal disorder that is characterized with

xantoms and atherosclerosis. Increase of cholesterol occurs due to low catabolism
of LDL and increased synthesis of LDL from IDL. This disorder is more expressed
in homozygote state where conc. go over 13 mmol/l with manifestation of
atherosclerosis before puberty. In heterozygote state concentrations don’t exceed
7.8 mmol/l.

Familiar defect of apo B: rare disease seen mostly in people with German origin.
Clinically is manifested as heterozygote familiar hypercholesterolemia.

LDL increased with tryglicerides

Familiar chylomicronemic syndrome: Deficinecy of lipoprotein lipase induces

dereased lipolysis. Chylomicrons are increased with VLDL and tryglicerides
exceed 11.3 mmol/l. This syndrome is seen in children and its characterized with
recurrent abdominal pain, translucent retinal blood vessels and eruptive xantoms
on the skin. There is no atherosclerosis.

27. Secondary hyperlipoproteinemia

Changes in lipoprotein levels can be seen in many disorders that affect lipid
metabolism.

Obesity is usually accompanied with it hyperlipoproteinemia. Increase in adipose

tissue together with insulin sensitivity has multiple effects on lipid metabolism.
Increased insulin stimulates secretion of fatty acids. These fatty acids go to liver
and they are esterified to tryglicerides that go in circulation together with VLDL.

Diabetes: In ketoacidosis tryglicerides increase due to great secretion of VLDL

from liver which is caused by bigger flow of fatty acids and low degradation of
VLDL

Hypothyreoidism is accompanied with LDL increase

Nephrotic syndrome is followed by hyperlipoproteinemia due to decreased

clearance and increased hepatic production of VLDL.

Liver (many ways)

Alcohol stimulates secretion of VLDL

Estrogen increases VLDL and HLD in liver

Cushing: increased corticosteroids increase VLDL in liver

28. Pathogenesis and consequences of atherosclerosis

Atherosclerosis is a process which thickens arterial intima due to infiltration of
white blood cells, lipids and collagen in subendothelial space. It can provoke
stroke, infarct and periphery artery disease. Usually is localized on bifurcation of
arteries where blood vortex occurs and most affected are coronary, splenic, renal,
cns, and periphery arteries. Growth of atherogenic plaque is happening in years
and clinically it can express itself as angina pectoris, ischemia and muscle pain.
Also it can happen acutely with complications like infarct. Primary etiological
factor for atherosclerosis is still unknown.

Due to damage on endothelia there can be collagen seen so aggregation of platelets

occurs. There is an release of coagulation factor XII so fibrin is produced.
Cholesterol and triglycerides pass through damage on intima and sediment
themselves in smooth muscle cells and macrophages hence cause necrosis which
leads to formation of atherogenic mash. Platelets release also mitogen factor so
transition of smooth muscle cells from tunica media to intima occurs. Three basic
atherogenic factors are: filtration of lipoproteins in arterial wall, aggregation of
platelets and smooth cell multiplication/migration in arterial wall.

Process of atherogenesis passes through several stages:

1st - endothelial damage

2nd – formation of fatty stripe on place of endothelial damage. These lesions are
small, rich in lipids, yellow colored and contain foamy cells. Foamy cells are
formed out of oxidized LDL that passed through phagocytosis.

3rd – transitory lesion. This lesion looks like fatty stripe but besides foamy cells it
contains also extracellular deposits (lipids). Monocytes and macrophages are
activated so there is an inflammatory response (cytokines). Cytokines stimulate
migration and multiplication of smooth muscle cells.
4th – Fibrous plaque. These lesions are going in lumen of blood vessel. They
contain lipid matrix, fibrous envelope and base that is made of smooth muscle
cells.

Lipid matrix – foamy cells, necrotic detritus and extracellular lipids.

Fibrous envelope – surrounds lipid matrix and it’s made of connective fibers,
fibroblasts, lymphocytes, mastocytes, macrophages and some smooth muscle cells.
It induces matrix growth since it increases components production that are found in
matrix (collagen, elastin)

Fibrous plaque can produce symptoms like ischemia. It represents a dynamic

formation that is growing constantly with a possible transition to complicated
plaque. Fibrous plaque can be stable and unstable. Stable ones don’t transform in
complicated plaques while unstable ones do. Unstable plaques contain big lipid
matrix, thin fibrous layer and active infiltration of inflammatory cells. Complicated
plaque will form when there is a rupture of fibrous layer. Rupture of fibrous
envelope exposes lipid matrix that has a strong thrombogeneous effect so
thrombosis can be seen. These changes can obstruct blood vessel fast and cause
acute ischemic consequences. Also, it can happen that atheroma content flows
through bloodstream (embolism).

Factors of risk for atherosclerosis:

Primary: males, diabetes, congenital hyperlipoproteinemias, arterial hypertension

Secondary: obesity. smoking.

29. Dehydration (isotonic, hyper, hypo)

Metabolism of water and electrolytes is a dynamic system where loss of water is
permanent while water intake is occasional. Body fluid is actually a solution of
different materials so there is actually no pure water. In body fluid all biochemical
reactions occur for basic metabolic processes (oxygen transport, elimination of
carbon dioxide, mediators transport, nutrition..). Body fluid is approx. 60% of body
mass and it’s divided in extracellular (40%) and intracellular (60%). Intracellular
fluid is found in the cells while extracellular in interstitium, plasma compartment,
lymphatic system and transcellular fluid (eye water, liquor).

Isotonic dehydration: In this type of dehydration water and osmolar active

particles are lost equally so tonicity in compartments is not changed. It’s seen in
vomiting, diarrhea, dieresis with diuretics, etc. Loss of isotonic liquid is usually
accompanied by electrolytic and acid-base disbalance. By vomiting acid is lost so
alkalosis is seen with decreased Cl and K. When burns occur some compensatory
mechanisms are activated so centralization of blood flow occurs, activation of
RAA system and centre for thirst activates so person drinks more. These
mechanisms are not enough so NaCl is administered. Clinically: hypovolemia of
plasma, low BP, colaps, tachycardia.

Hypertonic dehydration: loss of water is more expressed than osmolary active

particles. This happens due to low water intake or expressed loss of hypotonic
fluid. Volume is decreased in all compartments so this type of dehydration is also
called global dehydration. Usually it occurs due to increased perspiration of water
steam on high temperature, sweating and in some diseases where hypotonic urine
is excreted (AKI, CKI, diabetes). Clinically: tachycardia, thirst, dry skin and
mouth, irritability.

Hypotonic dehydration: Characterized by increased loss of osmolar active

particles. It’s seen in low salt intake or kidney diseases where retention of Na is not
possible. Clinically: most important are edema and increase in intracranial
pressure.

30. Hyperhydration (isotonic, hypo, hyper)

Isotonic: Water and osmolary active particles are increased equally with fluid
accumulation in intracellular space. Clinically it’s known as edema. Most common
mechanism that provokes expansion of intracellular space is low coloido-osmotic
pressure in plasma, higher permeability of capillaries, disorder in lymphatics, etc.
Decreased CO pressure can be seen in states where albumin is decreased so
hydrostatic pressure overcomes osmotic. Fluid transfers to intracellular
compartment. Low plasma volume activates RAA system which increases
hydrostatic pressure even more.

Hypertonic: accumulation of hypertonic liquid in extracellular space due to high

salt intake or its low excretion. Its seen in patients that go to dialysis whne their
water intake is higher than normal. Also it’s seen in Cohn and Cushing disease
(increased aldosterone, glucocorticoid). Clinically: increased blood pressure,
excitability of CNS, thirst.

Hypotonic: expansion of all compartments due to accumulation of hypotonic fluid

due to non controlled secretion of ADH or increased liquid intake in patiens with
CKI. All compartments are full. This is known as global hyperhydration or water
poisoning. Clinically most important is brain edema.

31. Isotonic dehydration and hyperhydration

32. Hyperkalemia and hypokalemia (Potassium)
From total amount of potassium 98% is intracellular and 2% extracellular.
Concentrations can vary in range of hypo/hyperkalemia.

Hyperkalemia: this is seen when intake of potassium is increased in kidney

diseases or when potassium is released from cellular space. Low excretion is seen
in AKI and CKI. Also it’s seen in Adison disease. In Adison low aldosterone
prevents active secretion of potassium and spironolactone (antagonist of
aldosterone) increases potassium.

Acidosis is also correlated to hyperkalemia. Compensatory mechanism for

correction of H+ ions is in transferring them to intracellular compartment where
H+ ions are exchanged for K. Neuromuscular excitability in hyperkalemia is
increased. Polarization is under action potential so the cell is depolarized and it
can’ repolarize its membrane again. On ECG T wave is bigger (increased
excitability of myocardium can lead to fibrillation)

Hypokalemia: this is seen due to low intake of potassium, increased loss of it or

transport from EC to IC compartment. Usually its seen in vomiting and diarrhea
that leads to alkalosis so loss of H+ ions is compensated on cellular level by
transfer of H+ from intracellular to extracellular where H+ is exchanged with K. In
kidneys retention of H+ occurs, Na is exchanged with K which decreases K even
more. Hypokalemia is followed by decreased neuromuscular excitability.
Polarization is above action potential so for depolarization much bigger stimuli is
needed. In striated muscles this is manifested as paresis or paralysis. In heart it’s
manifested as rhythm disorders (increased). On ECG QRS complex is big with
small or without T wave.

33. Disorders of acid-base balance: acidosis and alkalosis

Disorders of acid base balance can be life threatening especially when pH of blood
is under 7 (increased H ions) so patient can die from acidic coma or when pH is
above 7.8 so patient can die from tetany (seizures).

Acid base balance can be affected by many mechanisms like excessive formation
of H ions that overcomes lung and kidney capacity for excretion or due to
increased loss in vomiting.

Disorders can be respiratory and metabolic by cause, acute and chronic by duration
and compensated/non-compensated.

Acidosis: Based on mechanism for H ion increase it can be additional, retentive

and substractional. Aditional occurs when acid is added in anaerobic metabolism
(lactate), retentive in kidney insufficiency due to retention and substractional for
example when bicarbonates are lost in diarrhea so they are exchanged for H ions.

Metabolic acidosis: there is always bicarbonate decrease so other anions increase

like Cl. We differ acidosis with or without increase of Cl. Regardless the cause
increase in H ions is gradual so compensatory mechanisms are fully activated. Low
pH of blood stimulates respiratory centre so hyperventilation occurs which
eliminates carbon dioxide and carbonate acid. Kidneys are reabsorbing
bicarbonates.

Respiratory acidosis: Basic mechanism for its cause is low ventilation of alveoli
which brings down oxygen and increases carbon dioxide. It can be caused from
pulmonary diseases (pneumonia, edema, obstruction), depression of respiratory
centre or some injuries. It can be acute and chronic. Acute due to sudden
hypoventilation with expressed hypoxemia and hypercapnia. Hypercapnia
increases carbonate acid while hypoxemia increases lactates due to anaerobic
metabolism. In chronic due to prolonged hypoventilation cell puffer systems are
drained fast and compensation is obtained from kidney by secretion of H ions and
bicarbonate reasbsorption.

Alkalosis: low concentration of H ions due to increase in bicarobonates.

Metabolic: bicarbonates increase, pH, and pCO2 usually with hypokalemia. It can
occur due to loss of acid, vomiting, diuretics usage, hypofunction of adrenal
cortex. In physiologic circumstances kidney eliminates bicarbonates so alkalosis
will occur only if hypoperfusion of kidney is present.

Respiratory: occurs due to hypoventilation of lungs and increased excretion of

CO2 which decreases pCO2 and conc. of carbonate acid. It can be caused by many
factors and its divided in acute and chronic. Acute is characterized by low pCO2 of
limited time due to expressed fear, increased temperature, poisoning with aspirin,
etc. In all cases its consequence is stimulation of respiratory centre. Due to its
sudden character compensation is limited only to cell puffer system. H ions are
exchanged for K. Chloride goes out of red blood cells while bicarbonates enter so
bicarbonates concentration is increased but not enough. Chronic is not so common
and it occurs due to prolonged decrease in pCO2. It’s seen in adaptation to new
surrounding that is located on increased heights. Compensated by kidney.

34. Disturbance in energy balance – malnutrition, obesity

If in short time energetic intake is decreased or increased compensatory
mechanisms will take action like usage of reserves when energetic level is
decreased or increased thermogenesis and elimination if energetic intake is
increased. In bigger amount of time if intake is decreased always spending of
reserves will occur while if intake is increased excess will be stored as fat.

Malnutrition: It can be primary/secondary, acute/chronic.

Acute: it occurs due to sudden stop in intake of food. It can be lethal in 8-10 days if
water intake is stopped too or after 2 months if water intake is normal.

First phase of acute starvation lasts from 3-5 days. In this phase before fat and
muscle tissue glycogen reserves are used. Main organ for compensation is liver.
Liver is forming glucose so energy for brain is obtained and ketone bodies so
energy for muscles is obtained. Fatty acids that are formed with aceto aCoA go in
the liver. Since Krebs cycle is not possible beta oxidation occurs and ketone bodies
are formed. By gluconeogenesis energy for brain is formed. Protein synthesis,
enzyme synthesis and hormone synthesis is stopped.

Second phase represents adaptation of organism. Brain starts to use ketones for
energy. Protein catabolism is stopped due to ketones. Insuline is decreased hence
glucose utilization in tissues.Kidneys synthesize ammonia which puffers H ions
while from the rest of it gluconeogenesis occurs.

Third phase represents catabolism of proteins since all reserves are spent with
lethal outcome.

Chronic: occurs due to low energetic balance for prolonged time. Organism gets
adapted so lean mass is preserved, energetic needs drop down. Ketone is used for
energy and physical activity is decreased. Main characteristic is gradual
degradation of body fat and decreasing body weight. Edema can be seen in
abdomen due to water mobilization in order to fill places where fat was. In more
advanced cases protein degradation is increased, atrophy of all organs is seen
except brain.

Marasm - form of severe malnutrition characterized by energy deficiency

Kahexia – seen in terminal stages of malignant diseases, total body exhaustion.

Kwashikor – malnutrition due to food intake without proteins

Obesity: BMI above 30.0

Genetically it’s seen in families but it’s hard to determine genetic role from
environmental role. It can be primary (in some syndromes) and secondary

There are three types of obesity: lower body affected, upper and mixed.
Lower body fat deposition is associated with venous insufficiency and mechanical
complications

Upper – disorder in glucose tolerance, fat metabolism disorder, atherosclerosis, etc.

Mixed – hyperlipidemia, joint changes, sex hormones disbalance, atherosclerosis,

etc.

35. Pathophysiology of hypo and hypervitaminosis

Vitamins can be lipid soluble (A, D, E, K) and water soluble. Water soluble are
easily excreted by kidneys so there is no deposit formation while lipid soluble are
transported with chylomicrons and are not excreted easily.

Hypovitaminosis A: Vitamin A, known as retinol is lipid soluble vitamin. Its

reserves are located in liver and it has a role in formation of rodopsine and
rodopsine pigments. In its deficit keratinisation of skin occurs and decrease in
number of photosensitive molecules.

Hypovitaminosis D: Vitamin D is a sterole derivate. In nature is found in form of

ergosterole and dehydrocholesterole. These two forms with act of UV light become
cholecalciferole and ergocalciferole. Active vitamin D or hormone D is correlated
with calcium levels (induces absorption). Deficiency is manifested with low Ca
and P in blood, increased neuromuscular activity, decreased mineralization of
bones, bloating etc.

Hypovitaminosis E: Vitamin E is transported by chylomicrones and it makes its

reserves in liver and fat tissue. Its an antioxidant and important factor in
erythropoesis. It has vasodilative and antiagregational properties. Hypovitaminosis
occurs due to malabsorption of lipids so lipid peroxide accumulates which can
damage tissue due to oxidation. It can cause hemolytic disease and atherosclerosis
due to oxidation of LDL and lack of vitamin effect on blood vessels.

Hypovitaminosis K: Vitamin K is synthesized in intestines. Deposit is not formed

so deficit signs are seen in 3 weeks. In deficiency of vitamin K non active forms of
coagulative factors are formed so basic pathophysiological syndrome is bleeding.
Hypovitaminosis B: Vitamin B is found in cereals, reserves in our body are low
and mostly they are found in muscles.

B1 (thiamine): This vitamin is a coenzyme in metabolism of carbohydrates and it’s

significant also for transmission of periphery nerves. Deficit can occur due to
alcoholism or by low intake of this vitamin with food. Clinically cardiovascular
disorders are seen due to metabolic disorders and low energy levels. In muscles
atrophy is seen and bleedings in CNS. Bery Bery is a disease caused by vitamin B1
deficiency and it represents a heart insufficiency with edema (wet form) or weight
loss with muscular atrophy (dry form).

B2 (niacin): dermatitis, dementia, diarrhea (3D)

B6 (pyridoxine): anemia, periphery neuropathy, stones in urinary tracts and

dermatitis. It represents a risk factor for atherosclerosis and deep vein thrombosis.

B12: It has a role in DNA synthesis and myelin formation and it is associated with
megaloblastic anemia, changes in myelin sheath with damage of spinal cord.

Hypovitaminosis C: This vitamin acts as a cofactor for many oxidative enzymes.

It’s one of the most efficient antioxidants. Its deficiency is followed with low
synthesis of collagen, dentine, bony tissues. Clinically is known as scurvy where
changes of skin are visible, changes in bones and joints and frequent bleeding.

Hypervitaminosis: Usually its associated with lipid soluble vitamins since they
make reservers. Hypervitaminosis of vitamin E is not known and hypervitaminosis
of vitamin K is a very rare condition. Hypervitaminosis D is associated with
hypercalcemia, hypercalcuria and secondary hyperparathyroidism.
Hypervitaminosis A: toxic effects, loss of appetite, sleepiness and vomiting.

36. Effects of chemical factors on human body

Modern way of living has got us exposed to many chemical agents that are used in
industries, homes, etc. Every chemical substance in adequate dosage can provoke
damage. Toxin is a substance that can damage our organism even if the
concentration is small. Intoxications can be outer and inner.
Outer: Entrance of toxins is provided by food intake, water intake or inhalation.
Toxins that enter respiratory system are diffused in alveoli and go towards left
heart and then they pass in systemic circulation. By this liver detoxication is
bypassed. Usually other toxins enter our body through GIT which has a good
mechanism of detox provided by specific reactions that occur in liver. Toxins that
are soluble in water go in all tissues and organs while lipid soluble bind to plasma
proteins and release themselves in tissues for which they have bigger affinity.

Inner: Inner intoxication occurs due to accumulation of metabolites. It can occur

due to increased synthesis, insufficiency of organs for detoxication or low
excretion. (toxins example: combustive toxin in burns)

Mechanism of intoxication: Toxins can provoke damage on entrance site, on other

cells and tissues or on elimination spot. Local toxic effects are seen on entrance
site (mucosa of GIT, RT). If toxin is highly acidic then immediate necrosis will be
seen while if it represents a low irritant then transudation will occur with
hyperemia. On cellular level it affects the enzymes by their inactivation so
substrates accumulate. In elimination spot (kidney) it can damage tubules if
concentration of toxin is adequate.

Acute intoxication: nausea, tachycardia, pain, vomiting, diarrhea, etc.

Chronic intoxication: It will damage the organ or tissue where it acts the most.

Defense from intoxication: Done mainly in liver by P450 enzymes (cytochrome)

which are catalyzing biotransformation of toxins. This is also called metabolism of
xenobiotics and it can modify, conjugate or excrete toxins. Modification will
transform toxin in non toxic metabolite (or more toxic) for second phase reaction.
In conjugation substances pass to water soluble substances by reactions which
include sulfuric acid and glutathione. When substances are water soluble they can
be excreted by kidneys.

37. General and local effects of heat on human body

Humans have advanced thermoregulatory system which keeps body temperature at
36.5 degrees and it is more vulnerable to increased temperature.
For increased temperature organism includes all compensatory mechanisms to
maintain normal temperature which represents a compensated phase of
hyperthermia. When temperature still increases with all compensatory mechanisms
activated then this is called non compensated phase. In compensated phase
cardiovascular system is affected. Blood goes towards skin so it can giveaway the
heat. Respiration is increased. Tachycardia is present with increase in systole and
minute volume. Also sweating is present. If this reaction is prolonged then all
symptoms increase even more which can lead to dehydration. Afterwards
metabolic processes slow down which increase metabolism and temperature.

In non compensated phase CNS gets damaged, especially thermoregulatory centre.

Control over cardiovascular system is lost. Blood pressure drops, respiration
becomes difficult, hard and arrhythmic. Due to anoxia CNS is damaged, muscle
cramps occur with possible coma and death.

Hyperthermic collapse is not so severe disorder and it’s characterized by loss of

conscience in persons that are sensitive to heat. Vasodilation in compensated phase
is strong so blood pressure drops down expressively and acute ischemia of brain
occurs so patients lose conscience.

Heat stroke: this disorder is more severe and occurs when sweating is not possible
while person is physically active. Sweating stops due to damage of
thermoregulatory centre caused by temperatures that exceed 43 degrees. Skin is
warm, red and dry. Tachycardia, respiratory dysfunction and CNS damage.

Heat cramps: this is characterized by lots of sweating in compensated phase which

can lead to dehydration hence muscle cramping.

Adaptation to increased temperature: increased heart rate, temperature, sweating

and respiration. These become normal after time.

Local effects (burns): Known characteristics occur. For patients survival most
important is the skin % that is affected. In first 48h burn shock occurs where more
factors have a big role but plasmorhea is most important. Plasmorhea is increased
due to mediators which increase vasodilation. Consequences are hypovolemia,
isotonic dehydration with decreased blood pressure and hypovolemic shock. When
danger for burn shock has passed in first 7 days combustive toxins are formed
which are damaging all organs. If patient survives this then there is a new risk
since in this phase metabolism prefers catabolism. Water is evaporating out of the
injury site so bigger temperature must be generated and there is a possibility that
patient will fall in state of hypothermia. Most severe consequences occur due to
catabolism because there is no synthesis of immunoglobulins which leads our
patient to fall in state of immunodeficiency. Due to this infections can occur. Burn
when is opened and with exudates present represents a great platform for growth of
bacteria.

38. Effects of atmospheric pressure on human body

Atmospheric pressure at sea level equals 101kPa or 760mmHg. Changes in AP can
lead to damages if they are big enough and last long. Basic mechanisms are
changes in partial pressure of gasses in our body especially oxygen. Decreased AP
can occur in a fast or slow manner hence consequences differ.

Acute: Occurs due to expressed change in AP. This can occur for example when a
plane is rising fast on increased heights. Hypoxia occurs due to decrease in partial
oxygen pressure and CNS gets affected first since it’s most vulnerable to decreased
saturation. On 2.5km headache occurs. On 3km lack of interest, muscular
weakness and possible vomiting. On 5.5km muscle cramps are seen and on 7km if
there is no acclimatization patients can fall in coma. In acute hypoxia its important
to know that patient can lose conscience without any symptoms before. Also, on
heights more than 20km body fluids start to boil which can’t be connected to life.

Chronic: When staying longer on increased heights hyperventilation occurs so

hypoxia is compensated. Erythropoietin is more secreted so number of erythrocytes
is increased and capillary network grows in order to obtain more oxygen.

Chronic mountain disease: seen in sensitive presons on heights more than 3km.
Due to hypoxia hematocrit is increased with viscosity of blood which increases
blood volume and it can weaken the heart. Fatigue, loss of appetite, vomiting and
redness of eyes and face is seen.

Increase of pressure can occur when people are under the sea. Long staying with
increased pressure is seen in divers for example. Pressure on sea level is 1atm and
with every additional 1m it increases for 1atm. In prolonged staying in
circumstances of increased pressure solubility of gases increases hence certain
amount of nitrogen will dissolve. If the diver comes to the surface fast due to
increased pressure and decreased solubility of gases nitrogen will be released in
form of gas bubbles which can lead to embolism. By gradual coming to the surface
(main rule in scuba diving) nitrogen is released slowly through air. However if
symptoms like unconsciousness, colaps, bleeding in ears, etc. are present then
person is inserted in hyperbaric environment where pressure is close to 3atm and
free oxygen is given also to increase saturation.

39. Effects of speeding, vibration, sound and US and UV

Speed: small alterations in speed like traveling in planes or paragliding don’t have
any consequences but speeding in space shuttles or army planes for example have
since speeding is more than 1G. Consequences occur due to movement of small
structures in our body that are not in fixed position (blood, cerebrospinal fluid).

Speeding in cranial direction: 1G heaviness in lower limbs, 2 heaviness in all limbs

and feeling of pressure, 3-4 difficult movements and tachycardia with tachypnea, 5
black out and chest pressure, 6-8 coma.

Speeding in caudal direction: 1G pressure in chest from abdominal parts, 2 pain in

the face with red eyes, tachycardia and possible vomiting, 5 coma/death

Kinetosis (sea disease) occurs due to constant movement with vibrations.

Consequences occur due to vestibular apparatus (coordination) and n. vagus
stimulation (bradycardia, sweating, vomiting)

Vibrations: Mechanical oscillations on professions which can be local and

general. Damages that are local occur when using pneumatic hammer for example
so joints, blood vessels and bones are affected. Whole organism is affected when
the surface is vibrating (tractor driving). Tonus of muscles is increased, pain,
paralysis with headache and fatigue, beeping in ears, headache. Prolonged
exposition to vibrations lowers sensitivity to temperatures and pain. Tonus of
muscles and blood vessels is changed so arterial hypertension can develop.
Sound: Consequences can occur in range of acute acoustic trauma or chronic.

Acute can occur for example in explosions and usually the hearing ability is
damaged temporary. After sound strikes receptors for sound it lowers their
sensitivity so there is beeping, unclear hearing and feeling that our ears are
clogged. These are functional changes. If noise is over 120dB then ear drum can be
damaged, bony structures and Corti organ. Corti organ damage is the most
important. One fact is that damage is going to be greater if there is no perforation
of ear drum.

Chronic: when we are expressed to increased noise in prolonged amount of time

(85-95dB). Corti organ is affected. Hearing is first damaged for high frequencies.
Low concentration, fatigue and contraction of capillaries is seen. Total silence also
is not physiological and it’s expressed with feeling of anxiety.

Ultrasound: In medical usage ultrasound frequency is from 1-15MHz and it can

giveaway energy of 50mW(diagnostic), 3W (therapy) and 10W (surgery). Energy
that’s transmitted is converted to heat and mechanical energy with has multiple
effects. Physical effect is heating and mixing of fluids with particle oscillations that
can leave empty field in tissues. Chemically: reactions are faster, chemical bonds
are broken easily and ionization. Biological: low energies increase vital functions
and act as a stimulant. Increased energies can provoke cell death due to gel
aggregate state.

40. Effects of ionizing radiation on human body

Human body is always exposed to radiation which are basically electromagnetic
oscillations of different frequencies which posses different energy depending on it.
By energy radio waves are smallest in energy then IR, visible light, UV and X,
gama. All except X and gama rays don’t produce disorders.

UV effects: UV is electromagnetic radiation of 140-450nm. Sun is the biggest

source of this radiation. Its pure energy would be lethal but thanks to ozone energy
that is delivered to earth surface is about 290nm. Sun rays are classified in UVA
(400-315), UVB (315-280) and UVC (280-200). UV rays are absorbed by the skin
so they activate molecules which make photosensitive reactions (vitamin D). By
UV light photophysical, chemical and photobiological reactions occur.
Photophyiscal: absorption and activation of electrons. Photochemical: reactions
that occur due to absorption which make new structure. Denaturation of protein for
example. Biological effect: until some amount of UV they are good since they
have regenerative ability, catalysis of vitamin D, melanine formation but they can
have also bad consequences like solar dermatosis, changes in eye, cancerogenic
effect, etc.

Ionising radiation is form of electromagnetic radiation which gives away part of its
energy to surface that it came in contact. Electromagnetic rays are rendgen and
gama while corpuscular are alpha, beta and neutron rays. Sources of ionizing
radiation are everywhere due to natural radioactive elements like radone, radiation
from rocks, medical, cosmic, etc. Radone is seen only in places where uranium and
thorium are present because radone is formed out of them. Its HL is 3-8 days and
ventilation is effective for its elimination. Cosmic radiation is formed out of
protons, electrons and heavy ions. People who live on increased heights are more
exposed and pilots, astronauts, etc. In interaction between radiation and material
ionization occurs. It can provoke regeneration or death of the cell.

Factors influencing damage

Dose: 10Gy death in 1-2days due to CNS damage, 5-10 lethal due to GIT
complications, 0-5 changes in bone narrow and it’s not lethal.

Dosage: If one dose is received at a time it will make more damage than if givenin
parts.

Type of radiation: alpha and beta act on skin, rendgen and gamma on deeper
tissues.

Source: if outer radiation then distance, dose and time are important. If inner then
half life of isotope and type of organ that is affected are important.

Type of tissue: cells that divide the most are sensitive like lymphocytes, bone
narrow, stomach and intestinal epithelia and germinative cells while least sensitive
are hyaline cartilage cells and osteoclasts.

Acute radiation: it’s seen when big dosage is administered at once.

Initial phase: seen in 1st 48h after exposure. Vomiting, fatigue, loss of appetite and
other general symptoms are seen.

Latent phase: people look healthy

Manifestation phase: if dose is 1-3Gy then hematological consequences, more than

3 – hematological and digestive symptoms. Bigger dosages up to 20Gy can cause
cerebral damage. If 30 days pass patient has good chances for survival.

Recovery phase: it lasts from 3 months to 1 year. If death occurs it’s due to
infections. In this phase we should take care about patients hydration, possible
anemias, tumors etc.

Chronic: It occurs due to prolonged exposure to low doses and it can give
different symptoms.

Radiodermatitis: thin skin with ulceration and without hair

Cataract: blurring of eye lens

Leucopenia, anemia and infertility are seen often.

41. Etiology, pathogenesis and classification of heart failure

Heart failure is the state when heart can’t provide adequate minute volume of
blood according to physiologic needs. Minute volume is usually around 5l/min but
it can be increased up to 6 times. The cause of failure or insufficiency is usually
decreased contractility of heart muscle. This can occur by two mechanisms:
directly when pathology changes the heart structure (cardiomiopathy) and
indirectly when heart uses its reserves which leads to hypertrophy of heart which is
known as increased heart load.

Cardiomiopathies are different types of disorders which affect mechanism and

structure of heart. They can be dilative, restrictive or hypertophic.

Dilative are most seen. Pathologic process which affected myofibrils lowers heart
contractility. In diastole heart is freely filled up while in systole contraction is
decreased so the heart even in systole is enlarged. Systole and minute volume are
decreased so heart failure develops with all symptoms. To this form of failure
bring myocarditis, metabolic cardiomyopathies, connective tissue diseases,
ischemic changes etc.

Restrictive is when a pathologic process infiltrates heart with sediments or

connective tissue so heart is rigid and not able to enlarge good. This can occur due
to infiltrative process or granulomatous diseases.

Hypertrophic is not so common. Wall of left ventricle and septum is hypertrophic

and diastole is decreased due to rigid walls. Occurs usually due to genetic disorder
in heart structure.

Increased load can happen due to many disorders where heart uses its reserves

Preload: its enlarging myocard before beginning of contraction so heart in systole

pushes out bigger amount of blood

Afterload: every force that confronts blood pump in systole so myocard in systole
must use bigger force.

Consequences of load: Since heart must use bigger force to push out the same
amount of blood walls will become hypertrophic which will help for a moment. By
time heart becomes weaker and while contracting it cant push all the blood out so
blood will congest inside the heart – congestive heart failure.

Congestive heart failure is a sign that heart has used up all reserves. Heart is
hypertrophic and changes can’t go back to normal. Only muscle is hypertrophic
while blood vessels did not increase. This means that oxygen must pass bigger path
in order to enter mitochondria. Heart is in state of chronic ischemia and lack of
energy. Ca is not entering the sarcoplasm properly due to lower density of ion
channels in enlarged sarcoleme. This weakens contraction overall. Blood pressure
and minute volume drop down and this is stimulating baroreceptors to activate
adrenal system. Adrenaline influences vasoconstriction and increases
contraction/frequency. At the same time cells of juxtoglomerular apparatus activate
RAA system for water and Na retention in order to correct hypovolemy and
hypotension. This correction in state of heart insufficiency increases preload of the
heart hence worsens the situation even more.
Classification of heart failure:

Systolic when heart contraction is decreased so there is not enough blood pumped
out – dilative cardiomiopathy

Dyastolic when muscle is rigid so heart is not filled up adequately – restrictive and
hypertrophic cardiomyopathy.

Absolute: when heart with reserves can’t obtain desired amount of blood in
working and resting states

Relative: reserves in steady state are enough but not in working state

Hypovolemic: heart needs 5l but it provides 4l

Hypervolemic: heart needs 10l but it provides 8l

Retrogard: failure in front of heart so blood is accumulated in veins

Anterogard: failure behind the heart due to lower amount of blood in arteries

Acute/Chronic

Left/Right heart

42. Left heart failure

This represents signs and symptoms when left ventricle insufficiency is present.

Etiology: All diseases which affect left heart. Most common is arterial
hypertension when pressure is increased in aorta so left ventricle works more in
order to pump out the same amount of blood which represents afterload leading to
hypertrophy.

Pathogenesis: Myegenous dilation of left ventricle so blood in systole is not

pumped out enough hence blood congestion and increased pressure occurs in left
ventricle, atria and pulmonary veins. Lower amount of blood is pumped out in
periphery circulation.
Retrogard consequences: First consequences are seen in heart due to dilation and
enlargement of fibrous ring on mitral valve with functional mitral insufficiency.
First symptoms seen are inceased blood amount and pressure in lungs (congestion),
subjective feeling of choking, loss of breath and shortness of breath. Due to
increase of hydrostatic pressure there is transudation in interstitial space which
decreases elasticity. Muscles are using bigger force to maintain normal ventilation.
Dyspnea forces patient to breathe, there is no adequate oxygenation in musculature
so hypoxia occurs, acid metabolites accumulate so breathing is even more difficult
(due to H ions increase). By progression orthopnea (breathing heavy in laying
position) forms due to bigger amount of blood from limbs and abdomen that goes
in lungs. Patient is forced to stand up so symptoms can vanish. Later on cardial
asthma develops where interstitum and bronchial blood vessels are congested so
patient is coughing and choking. Pulmonary edema is the most severe
manifestation because congestion increases hydrostatic pressure in pulmonary
capillaries with transudation to alveoli so there is no diffusion of gases.

Anterogard: due to low amount of blood in aorta hypoxia of all organs occurs.
Kidneys, cns and skeletal muscles are affected the most. In brain respiratory centre
is affected by hypoxia. It’s less sensitive to increase in partial pressure of carbon
dioxide so there is cyclic change in apnea and hyperpnea. also changes like
confusion, anxiety, headache and memory decrease occur. In kidneys
hypoperfusion stimulates rennin secretion which acts on angiotensine and adrenal
cortex (aldosterone). Aldosterone is providing retention of Na which stimulates
ADH that reabsorbs water and leads to oliguria. Ischemia of skeletal muscles:
hypoxia, weakness, acid metabolites increase.

43. Right heart failure

This disorder occurs in those states where right ventricle must do more work. This
occurs usually due to barriers in pulmonary circulation. It’s seen mostly in
pulmonary hypertension.

Right heart deficiency forms due to dilation of right ventricle. Less amount of
blood is pumped in pulmonary circulation and right atria, ventricle and veins
accumulate blood. That represents a myogeneous dilation which is not capable to
pump out all blood in systole hence in front of right heart congestion of blood
occurs and increase of pressure in right atria, ventricle, cava veins and in big
venous creeks.

Retrogard: They happen first in heart due to dilation of fibrous ring dilation of
tricuspid valves. First symptoms occur due to blood congestion in cava veins and
its big creeks. Superior cava vein gives stasis of veins on the neck while inferior
provokes blood congestion in liver. Veins in liver are congesten and there is
pressure on hepatocytes and their ischemia, necrosis, reparation with connective
tissue which is called cardiac cirrhosis. Blood congestion soon takes over whole
venous system which gives cardiac edema due to transudation in intersitium of all
tissues. There is hypovolemy in arteries and RAA can’t compensate it. Secondary
hyperaldosteronism stimulates ADH so there is oliguria. Retentioned water goes in
edema – isotonic hyperhydration.

Anterogard: die to small amount of blood in pulmonary artery – cyanosis. There is

also a disbalance in perfusion/ventilation ratio so blood is not oxygenated good.
Later on patients are adynamic, skinny and weak – cardiac kahexia.

44. Disorders in mitral and tricuspid valves

Hemodynamic disorders in mitral valve:

1. Mitral stenosis: this worsens blood flow through valve from left atria
towards left ventricle during systole. Systole volume in left ventricle and
pressure in aorta is decreased. Left atria is overloaded and it dilates with
blood congestion in it so it goes back to pulmonary blood vessels which
leads to pulmonary congestion. All retrogard symptoms are seen (dyspnea-
ortopnea-cardiac asthma-p.edema). Later by progression left atria dilates
more, systole volume decreases which leads to pulmonary hypertension and
insufficiency of right heart. Also it can lead to absolute arrhythmia and
thrombus formation in brain.
2. Mitral insufficiency: blood from left ventricle goes back in atria during
systole. In diastole blood flow in ventricle is increased, it becomes
 hypertrophic so it maintains normal minute volume in aorta. This by time
leads to left heart insufficiency.

Hemodynamic disorders in tricuspid valves:

They are not seen so often and occur usually with mitral stenosis.

1. Tricuspid insufficiency develops in time of myogeneous dilation and right

heart insufficiency when fibrous ring dilates together with valves. Disorders
occur due to congestion and it can be seen instantly on neck veins (bigger)
and liver that becomes bigger.
2. Tricuspid stenosis: blood flow through valve from right atria to right
ventricle is more difficult during systole so left atria is under bigger pressure
so there is increase in diastolic pressure which goes back and congests big
veins. Main hemodynamic disorder here is possible regression of blood from
right ventricle in atria during systole which leads blood back to veins. These
pulsating dilated veins can be seen on the neck.

45. Disturbances in aortic valve disorders

Usually normal aortic orifice is 3cm^2 in cut section. When it goes under 1cm then
severe hemodynamic disorder occur which makes difficult blood flow through
aorta from left ventricle during systole. Ventricle is hypertrophic. Systole volume
is decreased and blood in aorta comes slower and in decreased amount. Pulse is
low and prolonged, systolic pressure is decreased while diastolic is increased.
Perfusion of all organs is decreased – hypoxia. Left ventricle is dilated and it can
lead to left heart failure.

Insufficiency of semilunar valve:

Blood flow through aorta in systole is without any disturbances but during diastole
there is regression of blood from aorta to left ventricle. Systole volume is
decreased by that part that came back while in aorta is the real systolic volume. In
diastole blood from left atria comes to ventricles plus the blood from aorta so
systolic volume is increased. Systole volume/effect systole volume should be 1/1
but here is 1.5/1 or 2/1. When it passes 4/1 then severe hemodynamic
consequences occur. Pulse wave is fast and high and its seen in capillaries. Systolic
pressure is increased while diastolic is decreased. Left heart insuficinecy.

46. Heart rhythm disorders – etiology and consequences

In order to perform its function heart besides using certain amount of force must
have rhythmical beats in certain frequencies. If arrhythmia occurs it can lead to
heart insufficiency due to decreased systolic volume. Arrhythmia also can
represent some myocardial damage so it has a great diagnostic value. Heart can
push out blood only if there is circular shortening of all muscle fibers at the same
time. Also relaxation is important and that atria fill up before ventricles so heart
can fill up adequately. All of these conditions are provided by autonomous work of
the heart. Normally conduction is generated in frequencies from 60-80 per minute
in sinus notch. From sinus notch it goes towards atrio ventricular notch where stays
a little and then through bundle of His is released on whole heart muscle almost at
the same time. In normal process of generation and conduction of excitation two
disturbances can occur: disturbances in generation and disturbances in conduction
of excitation.

47. Disturbances in creation and conduction of myocard

excitation
Disturbances in creation of conduction can be normotropic and heterotropic.
Normotropic are made in usual place but in different manner while heterotropic are
made in another place.

Normotropic: Conduction is made in sinus notch but in increased or decreased

frequency. Cause of this is always extracradial influence on sinus notch (neurotic,
humoral). Here belong:

Sinus tachycardia: Frequency is generated at 100-140 per minute. This can occur
due to increased blood flow through the heart or when blood pressure drops down
so baroreceptors inhibit n.vagus and sympaticus overtakes. It’s seen in physical
work, hypotension. febrile states, etc.
Sinus bradycardia: Frequency is generated under 60bmp due to vagal stimulation
from increased intracranial pressure, expressed hypertension or hypothyreoidism

Respiratory arrhythmia: Person has increased frequency during inspiration and

decreased frequency during expiration. This is physiological in younger people and
it vanishes by time.

Heterotropic: Ectopic centre that generates frequency is located outside the heart
(peacemaker). From inner centres every part of the heart can become ectopic centre
but it must have faster depolarization than sinus notch.

These arrhythmias can be divided by place of centre (atrial,ventricular), frequency.

Extrasystoles: impulses that lead to early contraction of the heart. Systole volume
in extrasistole is decreased while in normal systole it’s bigger so there is no
influence on minute volume.

Heterotropic tachycardia: 140-220bom generated by ectopic centre. Minute volume

decreased because heart in diastole cant fill up good.

Flatter: 220-350bpm

Fibrilation: over 350bpm Severe hemodynamic disorder, minute volume is

decreased, pulse is in deficit because contractions are weak. Usually it can happen
due to atherosclerosis, mitral stenosis, toxications, etc.

Disorders in conduction:

Excitation is made in normal place but not conducted well. More common is
decreased conduction. It can occur by extracardial factors (n.vagus) which
decrease excitability of the heart and slow down the conduction or directly by
damage of heart muscle (ischemia)

Decreased conduction or conduction block is divided in 3 degrees and by place it

can be sinoatrial, atrioventricular, branch block, branching block.

Sinatrial: SA notch cant conduct excitation forward but ectopic centres take lead so
there are no changes.
AV block: slower conduction from atria to ventricles. 1 st degree is only slower
conduction, 2nd every 2-3 impulse is conducted (bradycardia), 3rd stopped fully
(possible death)

Block of branch or branching: myocardium is depolarized by other ways so there

are no changes in hemodynamics.

48. Myocardial and pericardial diseases

Myocarditis: inflammation of myocardial wall due to infective agents which can
produce damage by direct invasion, toxins or damage by immunologic reactions.

Viruses are usually the cause and they damage heart by immunologic processes.
It’s hard to diagnose since it’s not much different from other viral infections that
produce only general symptoms. Its seen only when it brings to heart failure.

Pericardial: Diseases of heart sack. Some factors that influence relaxation of the
heart and contraction (fluid accumulation, ingrowth of heart with sack) can lead to
insufficiency.

Fluid accumulation: accumulated fluid presses the heart and makes diastole more
difficult. Hemodynamic changes depend upon amount of fluid and rate of
accumulation. If 200-300ml is accumulated at once it can stop diastole totally
(tamponade). If accumulated slowly, diastole is more difficult, minute volume
decreases and tachycardia is a compensatory reaction.

Ingrowth: when pericardium is thickened by fibrous tissue. Diastole and systole

more difficult. Tachycardia for compensation.

49. Arterial hypertension

Arterial hypertension is a state where arterial vlood pressure is above normal (110-
140/65-90) where diastolic has a bigger diagnostic value. It can be acute and
chronic.

Primary arterial hypertension (essential)

It’s a disease where hypertension is the only disorder with unknown primary factor
and by pathogenesis it occurs due to disturbances in mechanisms that are
regulating blood pressure (Na, minute volume). It has high incidence and risk
factor is atherosclerosis and heart diseases.

Possible etiological factors: genetic, adrenal nervous system (stress – cortisol),

kidney (increased rennin and Na sensitivity), retention of Na (blood pressure
increase and volume of blood).

Development is divided in three phases: 1st occasional increase of blood pressure

occurs that is connected with stressing situations and only systolic pressure rises. It
occurs due to sympatic nervous stimulation (tachycardia, volume increase)

2nd is fixed hypertension: Constant increased BP. Minute volume is normal.

Hypertension occurs due to vasoconstriction of small blood vessels which
increases periphery resistance (angiotensin is the cause). This phase can last long
and it leads to fixed tightening of arterioles so 3rd phase occurs.

3rd phase: hypertension with complications. On blood vessels there is hyaline

material so it leads to their decrease in diameter and ischemia of all organs.

Secondary hypertension (following other diseases)

Renal: almost all kidney diseases are followed by hypertension. It can be

parenchimal and renovascular. Parenchimal is seen in many diseases that produce
dysfunction of endocrine and excretory role of kidney. Renovascular is seen in all
diseases where ischemia of kidney parenchyma occurs it activates RAA system.

Endocrine: due to diseases mostly in adrenal, thyroid or hypophysis. In Cushing

disease mineralcorticoids are providing retention of Na and water. Some tumors of
adrenal medulla secrete adrenaline (increase in freq) and noradrenalin
(vasoconstriction). Usually most seen endocrine hypertension is correlated with
hyperfunction of thyroid gland because its hormones stimulate sympaticus and
increase sensitivity to adrenaline and noradrenalin.

Other: heart disease, changes in blood viscosity, pregnancy, tumors, drugs.

 50. Pulmonary hypertension
Pulmonry hypertension is a state where pressure in pulmonary artery is over
35/15mmHg and it occurs usually due to other diseases.

Due to mechanism of development there are 3 types:

1st passive pulmonary hypertension: seen in states where blood congests in lungs or
in cases of increased resistancy – cardiomiopathies, aortic and mitral disturbances,
hypertension (systemic).

2nd hyperkinetic pulmonary hypertension: due to increased blood flow through

lungs - atrial and ventricular septal defect.

3rd obstructive: when blood vessels are obstructed due to histological changes in
them. It can occur due to pulmonary diseases like COPD where capillaries are
reduced from destruction. This is the most severe form of pulm. hypertension.
Hemodynamic consequences: left ventricle gets less blood so minute volume is
decreased and increased resistance must be overtaken by right ventricle which
leads to its dilation and insufficiency.

Acute pulm. hypertension: It can occur due to massive embolism. Obstruction of

some bigger branch of pulmonary artery leads to hypertension which influences
heavily right heats. Symptoms are sudden: tachycardia, dyspnea, sweat, fear, pain.
Minute volume in heart drops down – hypotension – hypoxia – shock.

Chronic pulm. hypertension: Due to diseases which slowly increase resistance to

blood flow in lungs. Most common changes from chronic pulm. hypertension are
seen in right heart due to overload: dyspnea, tachycardia, cyanosis, thickened
fingertips (chronic pulmonary heart) Diseases that can lead to this are divided in 2
groups: parenchyma/airway diseases and diseases that limit movements of chest.

51. Arterial hypotension

Low pressure under 110/65mmHg and it can be expressed in several forms.
Primary: in some persons whose constitutional characteristic is 100/60mmHg and
that is normal for them. Some persons may experience it when passing from
horizontal to vertical position (dizziness) and it occurs due to late response of
adaptive mechanisms (vasoconstriction of blood vessels in lower limbs)

Secondary or chronic: pathological decrease in blood pressure in persons that had

usually normal BP and it can be a symptom of many diseases like adrenal
insufficiency, diarrhea, malnutrition, myocarditis, aortic stenosis, etc.

Tertiary or acute: expressed drop in BP that leads to unconscious state – syncope.

Causes of this can be vasomotor and cardiac

Vasomotor: drop in BP due to vasodilatation that can be seen in stressful states. It

never happens instantly so before it symptoms like sweating, nausea, weakness,
etc. are seen.

Cardiac: occurs instantly due to decrease in kick volume which influences blood
flow in brain (asystolia, fibrillation, infarct). Patient is without conscience, pale,
adynamic and without pulse.

52. Etiology and pathogenesis of shock

It represents inability of circulation to maintain adequate perfusion of vital organs
due to disturbance in capacity of blood vessels and blood volume. Crucial
pathophysiological change is slow and long lasting drop in arterial BP (mean
dynamic under 60mmHg)

Shock is classified due to causes of hypotension:

Hypovolemic – drop in blood volume usually due to bleeding

Cardiac – Most severe type of shock due to severe damage of heart muscle and
decrease in minute volume (infarct, infection, pulmonary thromboembolism)

Septic – due to invasion of bacteria in circulation

Neurologic – hypotension occurs due to vasodilatation that is caused by vasomotor

centre in CNS
Anaphylactic – 1st type hypersensitivity reaction mediated by histamine.

Disorders in microcirculation: Precapillary arterioles are under control of sympatic

nervous system from vasomotor centre which maintains their tonus. When arterial
vlood pressure drops microcirculation is putting effort to maintain the same
pressure for periphery tissues. Desinhibition of adrenergic part of VMC occurs
which o one side gives tachycardia and increased contraction and on other side
vasoconstriction in arterioles and sphincters. Vasoconstriction is mostly in skin and
spleen but if hypotension is prolonged then it affects other organs also.
Vasoconstriction in precapillary arterioles helps a little but it stops circulation
through capillaries. If hypotension cause is not removed microcirculation of tissues
is stopped (blood clotting). Also cellular metabolism is affected. due to hypoxia
cells pass to anaerobic metabolism so acid metabolites accumulate. Endothelia is
damaged and it becomes permeable for water and proteins. If at this point
circulation is recovered liquid part of blood goes out of capillaries and erythrocytes
accumulate even more which blocks capillaries definitely so necrosis will occur.

Clinical manifestations: in first phase tachycardia is seen and in second is

increased even more (up to 140bpm). Contraction of heart is decreased which leads
to insufficiency and in lungs inflammation and damage of alveoli lead to
respiratory insufficiency. In kidneys function is damaged which gives acute kidney
insufficiency with anura. Long ischemia affects first spleen and necrosis of
interstitial epithelia occurs (clinical sign: melena – blood in stool). Liver is
damaged also and bilirubine increases. Blood flow in cns is saved in first phase but
in second it is damaged so it can lead to depression and coma.

53. Etiology and pathogenesis of coronary insufficiency

Coronary insufficiency is the state when heart doesn’t get enough oxygen in
consideration with its needs and it can occur in 2 ways: low oxygen due to disorder
in systemic circulation or changes in coronary arteries.

Primary CI: due to atherosclerosis where it develops fast in coronary arteries due to
variations of blood flow (stop in systole, flow in diastole)
Biochemical changes in ischemia of myocard: Heart is capable to use many
supstrates for ATP production. In normal circumstances ATP is obtained via beta
oxidation of fatty acids and via lactate or glucose when needs are greater. In
ischemia and hypoxemia anaerobic pathway is used which from glucose gives
lactates and smaller amount of ATP. Lactates accumulate with H ions – acidosis.
Metabolic changes occur, no fat oxidation, no protein synthesis and ion pumps are
working in a slower manner. Ischemia decreases heart contraction and increases
relaxation. Kick and minute volume are decreased which represents acute heart
failure.

Electrophysiological changes: Ion pumps are slower and repolarization is late.

Repolarization goes from epicar to endocard which is inverted so inverted T wave
is present. Biochemical lesion gives elevation in ST segment.

Secondary CI: decreased blood amount in coronary vessels due to disorder in heart
or circulation. Disorders like aortic stenosis decrease blood systole volume in aorta
and coronary arteries. Changes in circulation that can lead to this state are
hypovolemic states such as bleeding or shock.

Degrees of CI:

1st – ins. only when states of increased needs are present but in steady states
normal.

2nd – both

3rd – blood flow stopped fully in one part of myocard: infarct.

54. Angina pectoris

This represents a symptom of coronary insufficiency. We differ stable angina in 1 st
degree of CI and non stable in 2nd degree of CI.

Basic characteristic is angious pain in chest that is periodical. Pain spreads in

shoulders, left arm, jaw and sometimes towards stomach. Pain is present due to
lactates from anaerobic metabolism which stimulates sympatic nervous system and
radiation of pain is due to transmission of sensitive fibers.
1st degree: Pain is related to precipitating factors (work, stress, digestion). Pain
lasts around 10 mins and vanishes when cause is removed.

2nd degree: Blood flow decreases so myocard is not working properly. Its
manifested with strong chest pain that can come unexpectedly. Pause between
attacks is usually around 1 month and then it gets more frequent. It lasts around
30mins. Vasodilators show effect after prolonged use.

Prince Metal angina is a rare form of angina due to spasm of coronary arteries with
or without atherosclerotic changes. Spasms occur due to hyperreactivity of
sympatic nervous system. It’s characterized by strong pain in younger persons that
occurs without any provoking factors.

55. Myocardial infarction

This is a state seen in 3rd degree of CI. Most common cause is thrombosis from
coronary arteries. Severity of clinical syndrome depends on amount of necrotic
myocard and speed of aterial clogging. If it took time new collateral blood vessels
decrease ischemia and other disorders. If it occurred suddenly then a big spectrum
of disorders occurs and even sudden death.

Biochemical changes: Oxygen reserves are used in 10sec, glycogen reserves are
spent by glycolysis and lactates are giving tissue acidosis. Ion pumps work slower.
Calcium accumulates and after 2mins there is permanent contraction and after 20
mins necrosis definitely occurred. Afected part is not contracting which affects
movements of myocard. Contraction is decreased overall, kick volume and minute
volume drop down together with blood pressure. Also this affected part cant relax
in diastole so diastolic pressure is increased and blood congestion can occur which
leads to acute heart failure.

Hemodynamic changes: decreased blood pressure activates baroreceptors resulting

in tachycardia. In normal circumstances it would be good but since heart is
damaged it makes the situation even worse and BP is not fixed. Pain occurs which
is similar to angious pain but is more intense and peristant. Another characteristic
of this pain is that it irradiates in all directions. This leads to cardiac shock.
Cateholamines are released and patient sweats but has cold skin (vasoconstriction).
Glucose is released from liver and fatty acids from fat – pseudo diabetic state.

Ecg: deep and wide Q tip.

Evolution: if patient survives 24h then demarcational inflammation occurs.

Enzymes remove necrotic tissue which gets changed with scarring tissue after 6
weeks.

56. Abnormal breathing patterns

QUANTITATIVE
Bradypnea: decreased frequency under 10pm – drugs usage

Tachypnea: increased over 24pm – excitement

Hypopnea: decreased breathing volume with normal frequence – sleep

Hyperpnea: increased breathing volume with normal frequence – athletes

Oligopnea: slow and shallow breathing with decreased volume and frequency –
sedation, cns disorder, increased partial pressure of carbon dioxide

Polypnea: fast and deep breathing with increase in frequency and volume – fear,
head injury, decreased partial pressure of carbon dioxide

Kussmaul breathing: hyperventilation with great increase in respiratory volume

without breaks – acidosis, intense work

Limited: hypo and olygopnea due to diseases where lungs are not elastic – fibrosis

Obstructive breathing: bradypnea, hyperpnea with specific sound of obstructed

airways.

QUALITATIVE:

Dyspnea: subjective feeling of difficult breathing in which we cant get enough air.
Seen in respiratory, CV, endocrine and other disorders. Objective signs are
trembling of nostrils and retraction of intercostals space. Clinically first manifested
when increased lung function is required. It can be acute (asthma) and chronic
(fibrosis). Dyspnea of CV origin is seen in left heart insufficiency or blood flow
disorders in left heart due to lung congestion se we need bigger pulmonary work
for proper ventilation.

Orthopnea: Clinical sign when patient sits to decrease dyspnea that is present in
laying position.

PERIODIC BREATHING

Chain stokes: changing periods between increased and decreased breathing volume
and apnotic breaks. Apnea lasts up to 50secs and it’s followed with increase of
ventilation to the peak and then back again gradually to apneya. Breathing hase
lasts from 30-40 cycles due to every state that decreases blood flow in brain.
Hyperventilation – hypocapnia – decreased ventilation

Biot breathing: severe disorder with disbalance in rhythm and depth of breathing.
Apnea shifts with deep or shallow breaths. It’s a sign of resp. centre disorder due to
tumor, heat stroke, intracranial pressure increase, etc.

Agonal breathing: complication of biot breathing that has a lethal outcome. Apnea
lasts longer and longer.

Singultus: sudden deep and fast inspirium with specific sound from epiglottis.
(hiccup)

Sleep apnea: apnotic attacks that last up to 20sec. They wake up the patient. Seen
due to cns damage, pulmonary obstruction, etc.

Hypoventilation in obese persons: mechanical due to fat tissue.

*** Normal breathing frequency: 12-20

57. Cough, respiratory bleeding, cyanosis, pain

COUGH – mechanism of airway cleaning with explosive expirium that is provked
by foreign particles, bodies, mucus, etc. It serves to protect lungs. It can be acute,
chronic, productive and nonproductive.
Productive or wet cough: mass is expelled out from lumen of airways or until
glottis and then swallowed. Depending on inflammation it can be purulent
(inflammation present) and squishy (no inflammation).

Nonproductive or dry cough: there is no coughing out. Acute is seen in initial

phase of inflammation. Chronic is seen in hypersensitivity of airways. Edema,
foreign body and pulmonary congestion for example produce this type of cough.

Abnormal sputum: In pathological states sputum mass increases or it can content

different cells. Increased amount is seen in bronchiectasia and tuberculosis. This
sputum has 3 layers. On bottom is dense, blurry and purulent. Mid layer is serous
and blurry colored green or yellow. Top layer is foamy and there can be seen some
purulent particles. Big amount of sputum is also excreted in drainage of pulmonary
abscess and this sputum has 2 layers. Bottom is again blurred and purulent and
upper is serous.

By look and consistency cough can be: serous, squishy (jelly like), purulent, with
blood, foamy, etc. Jelly like cough is seen in asthma. Foamy with blood is seen in
edema. Brick red color of sputum is seen in pneumonia. Black/gray is seen in coal
miners and smokers. Red and squishy is seen in pulmonary malignancies.

RESPIRATORY BLEEDING

Sputum with red filaments is called hemoptysis and when sputum is totally red
then it’s called hemoptoya. Hemoptysis indicates localized disorder like infection
or inflammation of bronchi and parenchyma. Hemoptoya can be caused by
carcinoma, edema, malignancy, congestion etc.

RESPIRATORY PAIN

This pain can come from pleura, airways or thoracic wall. Most common is pleural
pain which tightens pleura in infection or inflammation. Pain is localized on
thoracic wall above affected part. Pain is increased during coughing and laugh.
Pulmonary pain is registered as central chest pain and its location is retrosternal.
This pain also increases during coughing and laughing and it’s seen in patients
with inflammation of trachea. Thoracic wall pain is muscular or pain that comes
from ribs caused by excessive coughing.
CYANOSIS

Cyanosis is bruising or purple coloration of skin and mucosa. Visibility of cyanosis

is influenced by several factors like: skin thickness, capillaries and type of dermal
pigment. It occurs due to hypoxia and when in blood there is more than 5gr of
denaturated hemoglobin. There are two types of cyanosis:

Central – caused by excess of reduced hemoglobin in blood. It occurs in chronic

pulmonary diseases. Cyanosis is seen in buccal mucosa, tongue and lips. It
vanishes after inhalation of oxygen.

Periphery type – Mucosa is normally red and bruising occurs only on endings of
body (fingertip, nose, chin, nail bed). Hemoglobin is in normal range but blood
flow in capillaries is slowed down so skin that surrounds tissues provides increase
in desaturation of blood. Caused by decreased minute volume, vasoconstriction,
etc.

58. Disorders of ventilation

HYPOVENTILATION: alveoli space is not filled up with enough air so
oxygenation is disordered in capillaries and it leads to hypoxemia, hypercapnia
(increased pp of CO2) and respiratory acidosis. We can differ global and partial
hypoventilation of alveoli. Global is rare and it’s seen in advanced stages of
pulmonary parenchyma disorders, injuries, neuromuscular diseases of respiratory
muscles (tetanus, myasthenia gravis, dystrophy) and other. In partial type only
parts of lungs are affected.

Hypoxemia – causes cns disorder, hypertension of lungs/heart and heart

insufficiency.

Hypercapnia – causes disorders in cns regulation. Respiratory system is not so

sensitive on hypercapnia. Blood vessels in brain dilate which increases intracranial
pressure.

HYPERVENTIALTION: Occurs due to stimulation of receptors or respiratory

centre by brain diseases (meningitis), hypoxia, acidosis etc.
Hypocapnia: leads to fatigue, excitability, and dizziness due to vasoconstriction in
brain. Calcium drops down also so nerves are easily excited which leads to muscle
cramping

OBSTRUTIVE DISORDERS IN VENTILATION: Occurs due to decrease in

diameter of trachea and bronchi for 50-60%. It can occur suddenly or in stages
(tumor). Also it can be complete and partial. Most common cause is pathological
anatomical change in small airways (asthma, emphysema) with obstruction that is
chronically or acutely present. Main characteristic of OPD is difficult expiration.
Bigger force from muscles is needed or lung emptying is slower or there are both
present. Etiologically most important is smoking, pollution and professional
exposition to gases. Obstruction on level of small airways occurs in 2 ways: endo
and egsobronchial.

Endobronchial is caused by: decreased diameter due to mucus accumulation,

edema, bronchial spasm caused by histamine or cold air.

Egsobronchial: caused by increase in pulmonary elasticity that is reducing pushing

force and causes hyperinflation of lungs. When volume of air in lungs is ½ of vital
capacity influence of thoracic wall on inspiration is lost. Bronchial space gets
tighter and by time we have disorders in pulmonary cleaning – chronic bronchitis –
COPD. Consequences: pulmonary tension. Obstruction influences intrapleural
pressure with increased negativity on end of inspirium and positivity in expirium
(close to atm pressure) which leads to decrease in venous flow in right heart and
decrease in kick volume.

59. COPD and asthma

Asthma: reversible obstruction of airways by inflammation or hypersensitivity. It’s
a chronic inflammation with mastocyte, lymphocyte, neutrophil and eosinophilic
infiltration. Obstruction can be partially or completely reversible. Symptoms are
cough, expectoration of hyaline sputum, choking attacks and tension in thorax.
Provoking factors can be diseases such as infections or bronchitis, allergens,
inhalators, changes in temperature, etc.

Extrinsic asthma is allergic and it’s mediated by IgE (hypersensitivity type I)

Intrinsic: domination of indirect mechanisms in mid aged people caused by
infections and non specific stimuli. Pathogenesis is abnormality in autonomic
regulation of airways with increased release of mediators and vasoconstrictors. In
first minutes by cytokines edema is formed, constriction of bronchi and obstruction
lasts up to 1 hour. After 6 hours eosinophilic infiltration and inflammatory damage
is present after 24h.

COPD: Chronic obstructive pulmonary diseases are referring to chronic obstructive

bronchitis (endobronchial) and emphysema (egsobronchial). In chronic bronchitis
obstruction occurs due to inflammation, mucus and pus accumulation with
hypertrophy and bronchial spasm. In emphysema alveolar walls are damaged
which leads to loss in their elasticity and air gapping. Obstruction of airways is not
fully reversible and reduction of air passage is progressive. Etiological factors are
smoking and professional exposition to gases. COPD is common cause of right
heart overload.

Patophysiology of chronic bronchitis: Defined as hypersecretion of mucus with

wet coughing that lasts up to 3 months per year. Inhaled irritants increase mucus
and size of glands in resp. epithelia with harder mucus secretion that is a good base
for bacterial colonization. Alveolar obstruction leads to their hypoventilation –
hypoxia – hypercapnia – respiratory acidosis. Hypoxemia leads to vasoconstriction
in lungs, increased minute volume of heart, increased erythrocytes – hypertension
in lungs and right heart overload.

Patophysiology of emphysema: Permanent increase of acinous with destruction of

alveolar walls and capillary network. Cause of obstruction is loss in elastic forces
due to changes in lung parenchyma. Emphysema starts with dissolution of elastic
fibers in pulmonary connective tisse and destruction of alveolar septa so they lose
elasticity. Affected alveolar wall cant support and open bronchioles. Expirium is
difficult and air amount in acinous increases. Hyperinflation of alveoli makes big
air spaces. Septal destruction eliminates capillaries - hypertension. Hypoxemia also
occurs due to disturbed diffusion of gasses.
 60. Restrictive ventilator disorders
Disorders due to low compliance or elasticity of pulmonary tissue or walls that can
occur from:

*Thoracic diseases: all that influence expansion of thorax like deformations,

ankylosing spondylitis, fractures, fat deposition, etc.

*Respiratory muscles disorder: in severe weakness of muscles (myasthenia gravis)

*Pleural disease: in pneumothorax or pleural effusion due to pressure on

pulmonary tissue.

*Parenchimal destruction and decrease of active tissue (inflammation, tuberculosis,

tumor), decreased compliance (fibrosis) and collapse of tissue (athelectasis)

Patophysiological consequences: Disorders in pulmonary mechanics with lower

value and capacity. Alveolar hypoventilation occurs with disorder in air
distribution. Often blood capillaries are lost so disturbances in diffusion are also
seen, Hypoxemia with normocapnia or hypocapnia. Pulmonary work is increased
so dyspnea and tachypnea are seen. Right heart is overloaded which leads later to
insufficiency.

61. Pneumothorax, pleural effusion, atelectasis,

bronchiectasis,..
PNEUMOTHORAX is a presence of air or gas in pleural space which divides
visceral and parietal serous membrane that is pressing lungs and leads to their
retraction. It can be caused by rupture of pleura or thoracic wall.

Etiology: spontaneous is seen in young males due to rupture of visceral pleura with
unknown etiology. Sudden pleural pain is seen with tachypnea. Dyspnea with
possible collapse of lungs and hypoxemia is seen also. Secondary pneumothorax is
caused by trauma of chest, rupture in COPD and mechanical ventilation of lungs.
Pathophysiologically we have open pneumothorax and under tension. In open air
in inspirium enters pleural space and in expirium leaves. In tension place of rupture
allows entrance of air in inspirium but in expirium it’s not leaving out. This affects
lungs and leads to athelectasis. In mediastinum heart is moved with blood vessels.

PLEURAL EFFUSION is presence of fluid in pleura from blood or lymphatics.

Efussion is a result of disbalance between flow and absorption of fluid and proteins
from pleural space through vessels. Consequences are depending on amount of
fluid, type and speed of accumulation. It can change or move mediastinal content
and compress lungs.

ATHELECTASIS: collapse or non ventilated pulmonary tissue. It occurs due to

tumors, gas or liquid pressure (compressive athelectasis). It can occur also from
obstructed alveoli (absorptive athelectasis).

BRONCHIECTASIS is abnormal dilation of bronchi with obstruction of their wall

usually with other diseases. It can be cilindric, varicose, primary and secondary.
It’s caused by obstruction with mucus, athelectasis, aspiration of foreign body,
tuberculosis, etc.

DIFFUSE PULMONARY DISEASES: It contains more than 100 diseases with

different etiology. In common for all of them is pulmonary syndrome: diffuse
shadow is seen on x ray, low elasticity of lungs and restricted ventilation. Damage
of pulmonary parenchyma can occur via inhaled air or via blood. In inhalational
first alveoli are damaged and in systemic (via blood) first diffusion of blood
content in interstitum ad formation of inflammatory exudates occurs.

FIBROSIS: it can be a consequence of reparative tissue formation after disease.

Lesions can be focal and diffusive. Extensive fibrosis damages architecture of
lungs. Obliteration of alveoli occurs which leads to lungs with deformed cystic
alveolar space where alveolar epithelia changed and alveoli are smaller.

62. Disorders of ventilation – perfusion ratio (V/Q)

Decrease in this ratio occurs due to hypoventilation and it indicates existence of
functional shunt (venous-arterial shunt in non ventilated alveoli). In anatomical
shunts (congenital heart disease) we can differ that patient inhales concentrated
oxygen that decreases arterial-venous difference in pO2. Decrease in perfusion
ratio is seen in obstructive disorders of ventilation and atelectasia. Blood that
comes through is not well oxygenated which leads to hypoxemia. Hyupercapnia is
compensated by hypoventilation from normal pulmonary parts. Increase in this
ratio indicates alveoli that are not well ventilated and we talk in increase of blank
space or non useful ventilation of alveolar space. Increase in this ratio is seen in
embolism.

63. Disorders in diffusion/perfusion

Diffusion depends on alveolar properties and pressure of gas between alveoli and
capillary blood and partial pressure of gas in alveoli that is obtained by ventilation.
Factor is perfusion also which determines pp value in pulmonary capillaries. In
diffusive disorders we think on those that occur due to thickening of alveolar-
capillary membrane, thickening of capillary wall and expansion of intersitital space
(fibrosis, edema, infiltrations). Thickening of membrane will be seen also in
chronic blood congestion in lungs and in insufficiency of left heart. Due to basal
membrane thickening of capillaries diffusive surface is decreased. This is more
common cause and it’s seen in bronchitis, pneuomonia, edema, etc. Consequences
are decreased pO2 and pCO2 so hypoxemia occurs which leads to decrease in
blood volume in lungs and prolongation of contact between blood and alveoli.

Disorders in perfusion can be seen due to edema, pulmonary hypertension,

embolism, etc.

Pulmonary hypertension: pressure in pulmonary artery is over 30/15mmHg. It’s

not developed fast due to great adaptability of pulmonary blood network. Usually
it’s a secondary disease caused by any cardiac or pulmonary disease that increases
volume of blood or causes obstruction so resistance to blood is increased.

Embolism: occlusion in vascular network with embolus. Depending on severity

embolism gives different stages of hypoxic vasoconstriction, edema or atelectasis.

Pulmonary edema: it can develop slowly or fast. Typical is dyspnea in work with
progression to dyspnea in steady state. Orthopnea, hypoxemia and increased
breathing in work are seen also. Fluid gets accumulated due to disorder between
hydrostatic and oncotic pressure, increased permeability or decreased drainage via
lymphatics. Pulmonary edema is classified in:

 cardiac: pulmonary capillary transmural pressure is increased. It can be an

outcome of increased pressure in left atria, pulmonary venous hypertension
or increased volume of capillary blood in CKI. So cardiac edema is
hemodynamic edema. Hydrostatic pressure increases, fluid comes in
intersitium and it gets eliminated by lymphatics in beginning. Edemal fluid
here is trasnudate (protein content under 30g/l)
 non cardiac: it occurs due to increased permeability of blood vessels in acute
diffusive disorder of lungs (damage of capillaries or alveoli by toxins for
example). By pathology this is angiomural edema. Damage of alveolar-
capillary membrane occurs directly or indirectly. In lung damage main
factors are granulocytes, macrophages, platelets and mediators. Due to
damage and increased permeability plasma together with proteins leaves
capillaries and enters interstitium which increases oncotic pressure. when it
comes closer to hydrostatic pressure fluid goes to alveoli. Here we talk about
exudates since protein content is above 30g/l. Pathophysiology: transudate
or exudates in intersitium is decreasing functionality of lungs. Breathing is
shallow and fast. Dyspnea is seen with dry cough due to receptors activation.
Alveolar edema decreases compliance even more. More pulmonary parts are
with low V/Q and hypoxemia is seen too. Sputum is liquid that is foamy and
pinkish colored. Dyspnea, cyanosis, sweating, hypercapnia.

64. Patophysiology of respiratory insufficiency

It’s a disorder of pulmonary functionality caused by any cause that leads to direct
damage of lungs by hypoxic action that can be with or without hypercapnia. It’s
classified in hypoxic resp. failure and hypercapnic resp. failure.

Acute resp. failure is usually hypoxemic due to non adequate exchange of oxygen
between alveoli and capillaries. It can be caused by aspiration of foreign body,
atelectasis, cardial edema or pneumothorax. Chronic is usually hypoxemic with
hypercapnia caused by non adequate ventilation (toxins, cardiac arrest, shock, head
injury)
Pathophysiology of chronic

V/Q disorders: first disorder in pulmonary function is seen in patients with chronic
pulmonary diseases caused by non equal ventilation due to obstruction, perfusion
disorders or embolism. There are more stages. First alveolar hypoventilation
occurs which leads to respiratory failure. In hypoventilated alveoli saturation of
blood is low. This blood gets mixed with blood that is normally saturated (from
non affected alveoli) so there is a venous-arterial shunt that leads to hypoxemia.
This is chronic respiratory failure of distributive type. Diffusive type of respiratory
insufficiency is caused by diffusive disorder that originates from reduced capillary
network in fibrosis and emphysema. In this type hypercapnia is not compensated
which is depressing resp. centre in cns so it worsens the situation even more.

Low volume of minute ventilation: this is seen in states that decrease sensitivity of
respiratory centre and diseases that limit pulmonary movements. In chronic
disorders insufficiency develops slowly and it’s followed by hypoxemia and
hypercapnia that are well compensated. When saturation of blood by O2 is less
than 70% and pCO2 exceeds 60mmHg then it cant be compensated anymore.

Patophysiological consequences: Clinical symptoms depend on speed of

development. Defects are first seen in cns. For cns hypoxemia that is under
50mmHg will provoke damage and if it’s under 20mmHg then it’s lethal.
Hypercapnia above 90mmHg will depress respiratory centre and if it exceeds
120mmHg patient will fall in coma. Compensatory reaction from cns is increase of
minute volume by tachycardia which damages hearts contractility.
Vasoconstriction in splenic region with hypertension leads to transudation in blood
and muscles. Subepidermal edema is seen and increased sweating also. Central
cyanosis and polyglobulism gives a specific facial expression/look with sparkling
eyes. Terminal complication is cardiac arrest.

65. Patophysiology of hypoxemia and adaptive mechanisms

Hypoxia can occur due to disorder of any determinant of oxygen diffusion in
tissues. First affected are cells that are located away from capillaries.

HYPOXIA DUE TO INCREASED TISSUE ACTIVITY

This type of hypoxia is relative hypoxia that is seen when tissue increases its
activity and oxygen needs are bigger. In anaerobic metabolism we have oxygen
debt so muscle work is limited. due to lactates we get tired easily and lower pH
limits glycolysis. Protone circulation increases Ca binding to sarcoplas which
decreases contractility. Oxygen dept is seen in the beginning of muscle load and in
hypoxemy. It represents a difference between used oxygen and actual need for it.
also it can be defined as excessive use of O2 needed to metabolise accumulated
lactates and for ATP renewal.

PATOPHYISIOLOGICAL CONSQUENCES OF TISSUE HYPOXIA

Central disorder is on decrease of oxygen which decreases concentration of

compounds that are rich in energy and it increases reduced redox compounds (free
radicals). If hypoxia is circulatory also other nutritive compounds will decrease
aswell elimination of metabolic products. Regulatory mechanism with adenosine
monophosphate kinase in centre lead to change metabolism from aerobic to
anaerobic but here glycolysis is limited and metabolites increase. This increases
osmolarity and it can lead to cellular death. Lactates go in liver for
gluconeogenesis but in state of hypoxia liver function is limited so lactates
accumulate – acidosis. Due to stimulation of periphery receptors by hypoxia
hyperventilation will occur which eliminates more CO2 (alkalosis). Alkalosis
decreases sensitivity of hemoglobin for oxygen and increases diphosphoglycerate
in erythrocytes. Erythropoietin increases together with mass of erythrocytes and
blood is more viscous (resistant). Blood flow and O2 distribution decrease.
Systemic dilation confronts resistance which increases blood flow and minute
volume. Baroreceptors stimulate sympatic activity so vasoconstriction is seen in
skin, intestines and kidney (centralization of blood). Clinical symptoms can be non
specific. Fatigue, cyanosis and hyperventilation is seen.

66. Hyper/hypoparathyroidism
Parathyroid glands are endocrine glands and they synthesize PTH. Levels of Ca++
in blood by receptors regulate its activity, synthesis and secretion of PTH.
Cateholamines, cortisol and beta adrenergic stimulation increases PTG activity
while hormone D inhibits. PTH is considered as most potent regulator of
hypocalcemic states due to good mechanisms of detection and fast response.

HYPERPARATHYROIDISM

Primary: Disorder is in PTG with increased PTH in blood. Often is caused by

adenoma of gland. Dominant are two patophysiological mechanisms.
Hyperproduction of PTH and loss of action of PTG on increased Ca due to change
in gland itself. Increased PTH in blood affects kidney and bones directly while
enterocytes are affected indirectly. In kidney increase in PTH increases retention of
calcium. In bones it stimulates osteoclastic activity which increases calcium in
circulation. PTH increase in blood stimulates enterocytes to secrete calcitriole so
calcium is more absorber. Phosphate levels decrease. Clinical signs: in kidneys
there is nephrolithiasis, nephrocalcinose, damage of kidneys, polyuria, polydipsia,
nausea, ulcer, pancreatits, decreased bone mass, etc.

Secondary: it’s caused by pathologic changes that have prolonged decrease in

calcium so PTH is increased as a physiologic response. Primary cause is outside
the gland. Chronic decreased Ca levels can be caused by decreased intake or
malabsorption. Also its seen in terminal phase of CKI. Low Ca and P in urine.

Tertiary: it’s caused by autonomic hyperproduction of PTH as a response to

decreased Ca in late stages of CKI and patients on dialysis. In order for tertiary
hyperparathyroidism to occur first secondary must be prolonged.

Pseudo: when hypercalcemia syndrome and other manifestations are not followed
by increased PTH. Actually it’s decreased due to PTHRP which is secreted from
neoplasm in kidney or lungs and it has the same activity as PTH.

HYPOPARATHYROIDISM

Primary: seen when gland gets damaged by radiation, autoimmune diseases or

bleeding in glands. Most common cause is surgical removal which decreases PTH
since there is no gland. Clinically after 2-3 days due to low Ca muscular excitation
is increased – tetany (lock jaw, heavy muscle cramp)

Seccondary: PTG is intact which physiologically responds to increased Ca in

blood. Increased osteoclastic activity or vitamin D hypervitaminosis is the cause.
Pseudo: disorder is hereditary and seen mostly in females. It’s manifested as low
sensitivity of bone and kidney on PTH so there are no biological effects from this
hormone. Gland is intact. In blood calcemia is decreased and phosphatemia is
increased. PTH is increased.

67. Disturbances in calcium homeostasis

Hypercalcemia is a state where ionized and often total Ca are above reference
values. Causes of hypercalcemia can be divided in several groups with most
important ones that increase absorption, reabsorption and demineralization of
bones.

In primary and tertiary hyperparathyroidism PTH acts on bones, kidneys and

intestines so calcium levels are elevated. In some malignancies PTHRP is secreted
which has same action as PTH. Osteolitic metastases destroy bone tissue and
elevate Ca levels. Hypervitaminosis D and increased hormones in Adison disease
can cause elevation of Ca. In acidosis affinity for Ca binding is decreased so its
conc. is elevated in blood. Macrophages in some inflammations can synthesize
hormone D (increases Ca absorption)

Hypocalcemia: caused by disorders that decrease effects of hormone D and PTH

and by alternative mechanisms of Ca decrease. Hypovitaminosis D and decreased
production of hormone D in liver decrease absorption of calcium in GIT. Low PTH
in primary hypoparathyroidis and loss of biological effects of PTH on efector cells
shut down metabolism of bones so Ca is not released. Acute deposition of calcium
in soft tissue and hypocalcemia are seen usually in pancreatitis. Tissue is degraded
by pancreatic enzymes and free fatty acids bind to Ca so ionized Ca levels are
decreased.

68. Metabolic bone disease

In base of all metabolic diseases is one of modeling processes. Change in one of
many modeling factors can switch physiological to pathological way of bone
metabolism. Most common cause of metabolic bone disease is faster metaboolis
then decreased formation of bone with normal metabolism and as a rare cause
increased bone formation connected with non changed resorption. Fastened
metabolism of bone induced by any afctor increases level of formation/destruction
where osteoclatic activity is more dominant. Clinically most important are
osteoporosis and osteomalacia.

Osteoporosis most common bone metabolism disorder that is seen in mid aged
persons where females are more affected. It can be idiopathic and secondary. Basic
mechanism is increased metabolic activity with reabsorption of bone dominating in
the process. Loss of bone mass is seen mostly in lumbal part of back, upper parts
of femur and hip joints. Mechanical resistance is decreased and these can be places
of pathologic fractures. Concentration of calcium, phosphate and PTH are not
changed. It’s diagnosed by densitometry.

Osteomalacia: all diseases where mineralization of organic matrix is disordered by

vitamin D deficiency, metabolism of vitamin D or sensitivity to hormone D. When
bones that are developing get affected then disease is called rahitis. Both diseases
develop when osteoblasts produce osteoid but its mineralization is not sufficient
hence its thickness and volume increase but hydroxyapathite crystal impregnation
is disordered. Bones cant hold normal mechanical load so they deform. Usually it
occurs in long bones of legs, ribs and thorax. Most common cause of these diseases
is vitamin D deficiency due to low exposure to sun. Heavy damage of liver and
antiepileptics or tuberculostatics decrease hormone D production also. In vitamin
D dependant type of rahitis there is no vitamin D synthesis – type I. In type II
hormone D is usually elevated but sensitivity to it is decreased. Values of calcium
and phosphate decrease. PTH is slightly elevated.

69. Etiopathogenesis of caries

It’s a disease of hard dental tissue characterized by process of re/demineralization.

Demineralization occurs due to physical-chemical process between carbohydrates,
products of their metabolism and bacteria from plaque. On plaque bavetia
metabolise CH and produce organic acids and some proteolytic enzymes. Acid
diffuses through plaque and comes to the surface of tooth where it dissolves and
produces H+ ions. These ions get used up but calcium and phosphates from
hydroxyapatite induce degradation of acid hence new H ions are produced. From
enamel due to demineralization ions of Ca, OH, PO4, CO3, Na and Mg are
released. Process lasts until acid inflow is stopped. If ions of calcium and
phosphate diffuse slowly then balance between these two processes is obtained but
since new CH form new acids this cycle continues. Loss of mineral compound is
followed by disintegration of organic matrix which leads to cariogenic defect. In
normal circumstances tooth is always wet from saliva which can remineralize early
stages of lesion since it contains Ca and P ions in it. It means that carious lesion is
characterized by process of destruction and repair. Ca and P go thoruh and
remineralize damaged hydroxyapatite crystals. It can be spontaneous (saliva) and
stimulated (fluoride). For caries development 4 factors are needed: plaque, time,
carbohydtrates and spot that has great affinity for carious lesion formation.

70. Etiopathology of paradontopathies

Paradontopathy is caused by dental plaque and there are accessory factors that are
divided in two groups.

First: all agents which facilitate and fasten accumulation of plaque like anatomy,
food impaction, bad habits, lesions in gingival tissue and caries.

Second: all factors that influence general resistance of organism and fasten the
action of damaging agents in plaque like blood diseases, endocrine diseases,
toxins, aging, etc.

Dental plaque as primary etiological factor: this is a colorless, squishy sediment on

teeth usually made of bacteria. Other materials like materia alba (debris of food)
and pigmentations fasten accumulation of plaque. Base for plaque formation is
pellicle that is invisible sediment made out of glycoprotein and salivary lipids.
Pellicle evolves to plaque and microorganisms colonize. It’s formed on places that
are not able to self clean. It’s accumulated also in periodontal pockets so we differ
supra and subgingival plaque. Time for development and amount depend on
hygiene, salivary rate and type of food that we eat. 80% of plaque is water and
20% is organic or nonorganic with microbes dominating. Organic besides bacteria
has desquamated cells, mucine and leukocytes. Denatureated mucine is one that
makes aggregation of bacteria possible: after 2 ddays on pellicle gram+
streptococcus and baccilus are seen, after 4 days fusiform and gram- (mature
plaque) and after 9 days spiral bacteria can be seen. Locally it’s inflaming gingival
tissue.

Pathogenesis: paradontopathy starts with small asymptomatic lesions on gingival

tissue so it’s not seen in the beginning of diseases. Its caused by microorganism
and inflammation is a response to them. It’s exudative type of inflammation with
vascular reactions and those are first changes that are seen. Further on alternative,
degenerative and productive processes occur. Inflaming and destructive
degenerative processes need time to develop and they can never be stopped
spontaneously. There is degeneration of ligaments and other structures of
periodontium so in alveolar bone there is not enough support. Movements of teeth
with expulsions are seen.

71. Hypothyroidism
It’s a set of biochemical and clinical disorders caused by increased function of
thyroid gland with elevations in hormones.

Primary: in most cases is due to disorder in gland itself. Increased thyroid

hormones boost up basal metabolic rate and due to increase in oxidative processes
there is big amount of heat produced with increased energy usage. Food intake is
greater, absorption, spending of lipid materials with stimulation of glycogen and
protein degradation. Increased thyroid hormones stimulate sympaticus and
influence heart. Body temperature increases also.

Autoimmune hyperthyroidism as the cause of primary: Basedow disease

(enlargement of gland) is usually the cause. For this disease are characteristic
immunologic abnormalities, cellular infiltrations, genetic predisposition and
uncontrolled stimulation of thyroid gland which increases thyroid hormones. Its
said that autoreactive T lymphocyte or abnormal presentation of antigen are basic
mechanism for its development. In these patients autoantibodies for antigens of
thyroid gland are produced. Most important role in development have thyreo
stimulating immunoglobulins (TSI) that are made in cells of infiltrate and
extrathyroid lymph nodes. TSI bind to extracellular fragments of TSH receptors on
thyreocytes and activate them to synthesize thyroid hormones. Increased t3 and t4
block TSH but TSI works still.

Toxic adenoma: thyreocytes in nodular changes of thyroid gland increase thyroid

hormones. This nodal secretion is autonomic and non dependant on needs of
organism. Etiology is not so clear but probably there is a mutation on TSH
receptor. T3 and T4 increase and TSH decreases. Normal tissue of thyroid gland by
time becomes unfunctional

Thyreoiditis: Damage and necrosis in this inflammation can excrete TH reserves in

bloodstream. During and after therapy hypothyreoidism is possible (reserves spent)

Extrathyroid production of TSH: from ectopic tissue in teratomas of ovary or from

secretory metastasis of TG carcinoma.

SECONDARY: by changes in hypothalamus and hypophysis and it’s usually rare.

Hypersecretion of THS from changed thyreotropic cells in adenohypophysis. T3,

T4 and TSH increased.

Hypophysis resistance on TH: mutation on TH receptors in hypophysis occurred so

they are not sensitive to changes on TH in blood.

72. Hypothyroidism
State due to low secretion of TH and decreased biological effects. Mostly the
cause is due to disorder in TG due to inflammation, autoimmune or other
destructive disorder where parenchyma is damaged hence functionality. Low
TH can also be caused by iodine deficiency.

Secondary and tertiary hypothyroidisms occur due to non adequate stimulation

in hypothalamus or hypophysis. Low TH decrease metabolic processes, BMR,
heat, and inhibit sympaticus (bradycardia, hypotension, cold skin, etc.).
Decreased metabolic processes accumulate water soluble polysaccharides
which results as edema.

PRIMARY
Autoimmune: Hashimoto. In beginning gland is enlarged then infiltration
occurs that by time destroys gland. Lymphocytes are sensibilised on antigene of
thyreocytes. Most important are thyreoglobuline A and B. When TH decreases
TSH increases to maintain normal levels of TH.

Iodine deficit: decrease in TH. There is no adequate development of synapsis,

myelin formation is decreased and even mental retardation can be seen. Bones
are affected also which develop slowly.

Juvenile: decreased TH, slow development, decreased mental capability and

sexual development.

Other: after inflammation or radiation damage occurs. Reserves are used up so

hypothyroidism occurs which can be acute and chronic.

SECONDARY

Low TSH due to damage in adenohypophysis by tumor, bleeding, ischemia.

TSH decreases and in healthy TG there is decrease of TH.

TERTIARY

Cause is morphological and functional change in neurosecretory cells that

secrete TRH (thyroid releasing hormone). When we suspect this state skull base
must be examined and by lab thyrotropic cells and thyreocytes must be intact.
TRH test in these persons with low TSH and TH shows increase in them.

GOYTER

Enlargement of thyroid gland diagnosed by ultrasound or scintigraphy. It can be

enlarged diffusionally and nodally. It’s caused by tumor, inflammation and
edema. In simple Goyter usually we talk about enlargement that is caused by
prolonged stimulation with TSH or autoantibodies. Enlargement of thyroid can
be hyperthyroid, hypothyroid and enthyroid.

Low TH – adenohypophysis – TSH – TG – hypertrophy.

If TSH obtains normal TH levels then enlargement is enthyroid. If TSH can’t

obtain normal TH levels then it’s hypothyroid.n
 73. Disorders in adeno and neurohypophysis
Hypothalamic hypophysis complex is a functional connection between nervous and
endocrine regulation. Hypothalamus and hypophysis connection is direct. For
example anti diuretic hormone (ADH) and oxytocin are hormones of posterior
hypophysis lobe. These hormones are secreted in hypothalamus but stored in
hypophysis. Connection between hypophysis and adenohypophysis is obtained by
portal blood circulation. On peptidergic cells of hypothalamus adrenergic,
cholinergic, dopaminergic and serotoninergic fibers end which controls release of
peptides in portal circulation which later go to endocrine cells of adenohypophysis
and make effect. In hypothalamus 4 clinically significant stimulating peptides are
secreted:

TRH – thyreotropine releasing hormone which stimulates release of TSH and

prolactine

LHRH – gonadotropin releasing hormone stimulates FSH and LH

GHRH – somatotropine releasing hormone that stimulates growth hormone

CRH – corticotropine that stimulates adrenocorticotropine (ACTH)

In hypothalamus also inhibitory factors are secreted: somatostatine, opioid and

dopamine (inhibits prolactine)

DISORDERS OF ADENOHYPOPHYSIS

Hormones of adenohypophysis that stimulate other glands are: TSH, LH, FSH and
ACTH. TSH stimulates thyroid gland. LH induces ovulation and yellow body
formation in females. In males it stimulates Leydig cells to produce androgens.
FSH stimulates estrogen secretion and growth of ovarian follicles. In males
stimulates spermatogenesis. ACTH stimulates glucocorticod formation and
andorogeneous hormones.

Hormones that act directly on tissue are: growth hormone, prolactine and melano
stimulating hormone. Growth hormone stimulates multiplication of chondrocytes
and hyperplasia of sarcomere in musles. Indirectly it acts on metabolism in
anabolic manner (no catabolism, usage of fat, retention of ca for bones). Prolactine
stimulates milk production and it’s an antagonist of FSH and LH. Prolactine is
regulated by TRH and dopamine. TRH increases and dopamine decreases
prolactine. MSH stimulates melanin production in melanocytes.

HYPERFUNCTION OF ADENOHYPOPHYSIS (hyperpituitarism)

Usually affects one hormone and it can occur in 4 ways: due to tumor that secretes
hormones, tumor that is outside and acts as an ectopic centre, excessive stimulation
of hypophysiotropic hormones and when gland is damaged where its hormones act
so there is no inhibition of them.

Hypersecretion of tropic hormones

TSH due to tumor and in primary hypothyroidism

Increased FSH and LH are seen in states where primary hyperfunction of sex
glands is present.

Increased ACTH is usually due to autonomic production from tumor.

MSH is increased in hypocorticism (cortisol is the inhibitor) so skin and mucosa

are too dark

Hypersecretion of growth factors

Tumor in adenohypophysis or overstimulation by GHRH is the cause. It leads to

increase in metabolism that is seen in bones mostly. If hyperfunction occurred
before bone closing then epiphysis in long bones is affected (gigantism). If
hypersecretion occurs in adults then bones will be thicker. Also nose, lips and ears
get bigger. Persons have characteristic look (acromegaly) and organs get bigger
(visceromegaly). By visceromegaly heart is affected since coronary blood vessels
are not big enough. Systolic volume increases, ischemia and a. hypertension are
present which leads to congestive heart failure. Glucose tolerance is decreased so
there is hyperglycemia. Insulin is secreted more and by time B cells are used up so
this can lead also to diabetes.

Hypersecretion of prolactine

It occurs primary due to secretion from autonomic tumor which compresses other
structures or microadenomas. In secondary form there is no inhibition by PIH
(prolactin inhibiting hormone). Regardless the cause symptoms are galactorrhea
and amenorrhea.

HYPOSECRETION OF ADENOHYPOPHYSIS

Hyposecretion leads to lack of hormones from one group (selective) or all of them.
Selective is seen in hereditary diseases and affects one hormone or decreases
stimulation (seen in cns disorder)

TSH hyposecretion will result in secondary hypothyroidism. Decreased levels of

FSH and LH will lead to infertility and loss of secondary sex characteristics.
Decreased ACTH leads to secondary adrenal cortex insufficiency with pale skin
due to low MSH so its easily differentiated from primary form. Decreased
prolactine leads to hypo or agalactia. If decrease of growth hormone is present in
kids then they will develop slow and metabolically they will have hypoglycemia
due to increased insulin that is dominating.

HYPOSECRETION OF ALL HORMONES (PANPITUITARSISM)

Tumors of hypophysis or metastases that produce severe damage are the cause.
There is no secretion. If it develops in kid then that kid is going to be a midget with
hypothyroidism. Sexual characteristics will not be seen. Fatigue and hypoglycemia
present. This is a severe disorder which leads to drop in all functions and loss of
body weght. People suffering from this are not resistant and usually die from
adrenal insufficiency.

NEUROHYPOPHYSIS DISORDER

From neurohypophysis ADH and oxitocin are released. ADH acts on distal and
collective tubules so there is reabsorbtion of water. If osmolarity of plasma
increases then osmoreceptors in hypothalamus will secrete this hormone, transport
it to hypophysis and excrete. Urine is more concentrated and osmolarity is back to
normal.

Oxytocine acts on milk secretion and contractions of uterus in females. In males it

aids to push out spermatozoids in seminal fluid.

Hypersecretion of ADH: it can occur due to disorder in cns which affects secretion
(meningitis) or due to drugs usage. Commonly increased ADH comes from ectopic
tumors (lung, pancreas). Secondary increase of ADH is seen in all states that affect
plasma osmolarity (hydration). Consequences are increased water retention which
leads to hypotonic hydration and hyponatremia. Urine is hyperomolar and plasma
is hypoosmolar. Symptoms are headache and by progression water poisoning is
possible (bradycardia, cramps, coma)

Hyposecretion of ADH occurs usually due to damage in cns. Consequence is

increase of urine with low osmolarity. In plasma hypertonic dehydration induces
increase in water intake – diabetes inspidus. Hyposceretion can also occur due to
low sensitivity of tubules to ADH.

74. Hyperaldosteronism
Aldosterone is increased due to changes in zona glomerulosa itself or due to
disorder that stimulates this zone.

Primary: change in adrenal cortex. In 90% of cases the cause is adenoma that
autonomously secretes aldosterone , hyperplasia of this zone or some carcinoma.
Clinical symptoms are called Conn syndrome and this is seen more in females.
Increased aldosterone keeps Na in kidney with water together so hypervolemia will
occur with hypertension. Due to hypervolemia in heart there is peptide secretion
that doesn’t allow retention of Na in proximal tubules so there is no edema.
Chronic hyperproduction of this hormone will lead to hypertonic hyperhydration
and acid base balance disorder. Hypocalcemia and alkalois are present and
sometimes hypochloremia. Alkalosis leads to cramps. Due to hypervolemia in
arterioles of kidney there is decreased activity of RAA system, rennin is
decreased.

Secondary: it’s not a disorder. It’s fully physiological response to increased RAA
activity that has a role to remove hypoperfusion of arterioles in kidney which
stimulate RAA. Basal cause is outside adrenal part and they can be divided in:

1st – arterial nephrosclerosis in CKDs and changes in arteries of kidneys

2nd – all changes that reduce volume of blood or blood pressure are the cause so
RAA gets activated. All factors of dehydration, insufficiency of heart, decrease of
arterial tonus, etc. lead to this. Regardless the cause it indirectly activates RAA
which leads to 2nd hyperaldosteronism and aldostenore compensational response
cant be universal. If 1st etiological factor isn’t removed then this mechanism of
kidney can get contraproductie (congestive h. failure, edema). In blood rennin and
aldosterone are increased.

75. Hypercorticism
CRF (corticotrophin releasing factor) from hypothalamus stimulates ACTH in
hypophysis. In adrenal cortex ACTH stimulates production of cortisol and adrenal
androgens. It’s not having effect on mineralcorticoids. Cortisol inhibits ACTH.

Cushing syndrome: here belong symptoms that occur due to increase in levels of
cotisol. Increased levels are caused by hyperproduction in zona fasciculate by
adenoma or carcinoma, ectopic secreting centre of ACTH or nodular dysplasia of
adrenal cortex. Increased cortisol decreases CRF and ACTH. Since there is no
adequate stimulation of adrenal cortex by ACTH it atrophies slowly and cortisol is
constantly increased by autonomic adenoma production. By ectopic production of
ACTH (tumor in lungs or pancreas) due to permanent stimulation there is
hypertrophy of adrenal glands with increase in cortisol. In egsogeneous Cushing
(medication): atrophy and loss of gland function.

Cushing disease: hyperproduction of ACTH and increase of it in blood which leads

to adrenal hyperplasia and increased cortisol levels. In adenoma of
adenohypophysis ACTH increases and stimulates cortisol. Levels of ACTH and
cortisol can’t be brought down by corticosteroids. Clinically redness is seen, fat
deposition in neck, shoulders and waist. Skin is thin and fragile, muscle mass is
decreased, bone demineralization, psychic disorder, etc.

76. Hypofunction of adrenal cortex

Changes in adrenal cortex are primary form and disorders in regulation are
secondary form of hypercoticism.
Adison disease: primary hypofunction of adrenal cortex which affects all three
zones (global failure). Usually the cause is autoimmune destruction or tuberculosis.
In beginning secretion of adrenal hormones is fine and signs of failure are
expressed in stress (infection) when functional reserves decrease and they cant
produce enough cortisol. When 90% of parenchyma is destroyed patients are prone
to hypoglycemia. Low cortisol levels stimulate CRF and ACTH. Besides ACTH,
MSH is also released so there is hyperpigmentation. Global destruction of adrenal
cortex decreases aldosternoe so there is no water retention. Sodium levels are low,
hypotonic dehydration present, plasma volume is decreased and hypotension
occurs. All of these changes can lead to shock. Hypovolemia of kidney arterioles
increases rennin and production of angeotensine but there is no aldosterone so K
and H ions in tubules aren’t removed which means that there are hypercaliemia and
acidosis present.

Secondary hypofunction: disorder is in hypothalamus. ACTH is decreased hence

cortisol. If ACTH decrease is persistent there is atrophy and functionality loss in
adrenal cortex. Destruction of secreting cells in adenohypophysis usually occurs
due to ischemia, bleeding, tumor, etc. so adrenal failure is followed also by
decreased GH, PRL, TSH and gonadotropic hormones. Since there is no ACTH
there is no MSH also and skin is pale.

Acute insufficiency: this is a severe urgent state that occurs due to expressed fall in
hormones. It’s seen as a consequence in stress after trauma, surgery and severe
infections.

77. Hyperfunction of adrenal medulla

Medulla together with sympatic nervous system is sympaticomedullar functional
system. In medulla adrenaline, noradrenaline and dopamine are made. These
cateholamines are released by sympatic activation (work, hypovolemia, glucagon,
hypoxia). They make their effect by binding to specific alpha and beta receptors.

Hyperfunction will increase cateholamins in blood. Tumor production

(pneochromocytoma and paraganglion) can also increase these levels. tumor
production of cateholamines is characterized by higher levels of noradrenaline than
adrenaline. Clinical sign in tumor production is hypertension that is constant or
provoked by heavy emotions (tachycardia, sweat, redness). Also this production
induces glycemia and in muscles glucose is metabolized to lactates.

78. Disorders in sex glands

DISORDER IN FEMALE SEX GLANDS

Hypofunction of ovaries is reproductive life is manifested by menstrual cycle

disorder, lack of ovulation and even infertility. Due to low estrogen in patients (age
dependant) there is sexual infantilism or loss of secondary sexual characteristics.
Before puberty there is regression of primary sexual characteristics with lack of
secondary. If it happens in puberty amenorrhea is seen. Also it can lead to
osteoporosis and arteriosclerosis.

Primary hypofunction: due to damage of parenchyma so there is no enough

estrogen. Due to low estrogen there is secretion of LH and FSH from
adenohypophysis byt there is no compensation which is called
HYPERGONADOTROPIC HYPOGONADISM. Causes are: surgical removal,
climacteric atrophy of ovary or genetic diseases.

Turner disease is a hereditary disease where there is no X chromosome with lack

of estrogen production and disorders in growth. In climax there is loss of number
of ovarian follicles. Special entity is syndrome of polycystic ovaries. This disorder
contains elements of primary, secondary and tertiary hypogonadism. These patients
are obese, with amenorrhea and they are infertile. Potential cause is disorder in
hypothalamic-hypophysic base. Insulin/resistance is increased together with
androgens. There is aromatization of fat from androgen to estrogen which inhibits
FSH/increases LH. Decreased FSH blocks development of ovarian follicles so
there is no ovulation and increased LH leads to hyperplasia of ovary cells and
theca cells which secrete androgens.

Secondary hypofunction: cause is not in ovary but in adenohypophysis.

HYPOGONADOTRPIC HYPOGONADISM. Usually this is seen in
panhypopituitaris, bleeding and tumor of Turkish saddle.
Tertiary hypogonadism: changes which decrease LH-RH so there is no FSH and
LH which leads to loss of menstrual cycle. Usually it’s caused by inhibition from
cortical and subcortical structures of cns on secretory action in hypothalamus.
Functional causes of amenorrhea are emotional swings, fatigue and anorexia. Also
centre for hunger is affected so patients gain weight.

DISORDER IN MALE SEX GLANDS

Hypogonadism is decreasing reproductive and endocrine function of testicles

(testosterone, spermatogenesis). It can be primary, secondary and tertiary. All
hypogonadism states are characterized by drop in testosterone levels. Regardless
the cause clinical manifestations are similar. In kids there are no primary and
secondary sexual characteristics. If it occurs in adults then they will lose libido and
potency.

Primary: damage is in testicle itself. Low testosterone stimulates FSH and ICSH
(interstitial stimulating cellular hormone) to correct it. This is
HYPERGONADOTROPIC HYPOGONADISM.

In Klinefelter (XXY trisomy) besides normal hypogonadism there is gynecomastia.

Spermatogenesis is not present.

Castration and massive trauma are also causes of hypogonadism and if it occurs
after pubery secondary sexual characteristics will slowly degrade

Secondary: HYPOGONADOTROPIC HYPOGONADISM. FSH and ICSH are

decreased which results in low testosterone production and decrease of
spermatogenesis in healthy testicle.

Adiposogenital dystrophy and Callman syndrome are usually the causes that
damage neurosecretion of LH-RH. In Callman syndrome there is also disorder in
perception of smell.

Tertiary: hypogonadism from hypophysis usually caused by inflammation,

bleeding, ischemia or compression of adenohypophysis. There is no proper
function of testicle due to decrease in gonadotropic hormones.
 79. Etiopathogenesis and type of anemia
Anemias are hematological disorders where blood has decreased ability for oxygen
transport (decrease in erythrocytes, hemoglobin). Anemia decreases oxygenation
of tissue and provokes damage. Compensatory mechanism which are able to
correct anemia include: changes in hemoglobin dissotiation, centralization of
circulation, changes in cardiovascular system and increase in erythropoietin.

In anemias that are sudden (bleeding) all blood contents are lost equally and
clinically: dyspnea, tachycardia, decreased pulse, decreased pressure and shock. If
anemia occurs gradually symptoms are seen usually in working states: fatigue,
dizziness and pale skine. With progression heavy breathing occurs, arrhythmia,
angious pain, cramps and decreased focus.

Anemias are classified:

Due to disorder in erythrocyte maturation – hypoplasia of bone narrow, disorder in

nucleoprotein synthesis

Due to disorder in hemoglobin – metabolism of Fe disorder, synthesis of hema,

synthesis of globine

Hemolytic anemias – corpuscular or extracorpuscular

Blood loss anemia are classified due to size of erythrocytes (normocytic,

micro/macrocytic), hemoglobin content (normo, hypo, hyperchromic)

80. Anemia due to stem cell disorder

Aplastic anemia: disorder is in pluripotent stem cell. In bone narrow there is
reduction of hematopoietic tissue that contains lymphocytes and reticulocytes
which gets changed with fatty tissue. In blood red blood cells, platelets and
granulocytes are decreased (pancytopenia). Besides signs of anemia there are signs
that occur due to decrease in platelets and granulocytes. It can be acquired and
hereditary.
Hereditary besides aplasia has disorder in other organ systems. Acquired occurs
due to drugs usage, radiation or severe infections.

Heavy aplastic anemia: white blood cells are under 0.5x10^9 and platelets are
under 20x10^9. It’s diagnosed by biopsy of bone narrow, normocytic with
decreased reticulocyte number.

Isolated aplasia of red cell line: disorder of certain stem cell for erythropoesis and
it’s characterized by normocytic and normochromic anemia. Acute form is usually
due to aplastic crisis of hemolytic disease or infection while chronic occurs due to
autoimmunity.

Paroxisimal nocturnal hemoglobinuria: acquired stem cell disorder with changed

membrane of hematopoietic cells so they are sensitive to complement. Hemolytic
anemia is in the beginning and by progression it passes to aplastic. Etiology is
unknown. After activation of complement hemolysis occurs. Often thrombosis is
seen due to activation of platelets and ADP that comes from denaturated
erythrocytes. This anemia is normocytic, normochromic and characterized by
hemoglobinuria.

Myelodysplasia: Clone disease of stem cell characterized by dishematopoesis

(disorder in proliferation, differentiation and maturation). Anemia, decreased
platelets and granulopenia with normo or hypercellular bone narrow. Etiology is
unknown and it’s seen in older people.

81. Anemia due to Fe disorder

Every molecule of hemoglobin is consisted of two globin chain pairs with hema
molecule that contains Fe that is necessary for oxygen binding and transport.

Metabolism of Fe: absorber in duodenum and jejunum. When it passes epithelia it

binds to transferin and goes in tissue. Feritine is also important (complex of Fe and
apoferitin) and hemosiderine that is found in erythroblasts in bone narrow. Up to
50% of erythroblasts contain granules of hemosiderine and they are called
syderoblasts. Feritin amount = reserve of Fe in organism. Low Fe can occur due to
many factors: food, diarrhea, bleeding, etc. If not treated it can lead to syderopenic
anemia. Besides basic symptoms these are seen: fatigue, dyspnea, tachycardia,
tongue is smooth and red with inflammation.

Syderopenic anemia: occurs gradually. In first phase Fe reserves decrease,

hemosiderine is decreased also so there are no sideoblasts. Feritine decreases with
normal Fe in serum and transferine saturation. By progression transferin is more
synthesized in lver and serum Fe drops down. Organism uses all Fe to synthesize
hemoglobin. Hemoglobin also drops down and erythropoesis decreases.
Erythrocytes are normal in beginning together with white blood cells while
platelets increase. Diagnosis is set: low feritine, no sideroblasts, Fe decrease and
transferin saturation decreases.

Syderoblastic anemia: characterized by ring like syderoblasts where mitochondria

are full of Fe around nuclei, hyperplasia of red blood cell line, non efficient
erythropoesis, microcytic hypochromic red blood cells in blood with increased
feritine and transferin. It can be acquired or congenital. Congenital affects more
males (x chromosome).

82. Megaloblastic anemia

Occurs due to disorder in DNA synthesis and affects cells and tissues that are
divided fast (hematopoesis, GIT tract). Most megaloblastic anemias occur due to
decreased B12 and folic acid. B12 is found in milk and meat while folic acid in
most of fruits and vegetables. This vitamin is not degraded due to complex with
inner factor from parietal cells so it is binding to recetpros and eneters erythrocytes
in terminal ileum where factor is only degraded. Transcobalamine takes B12 and
transports it to other tissues. Active form of B12 is metilcobalamine. Common for
all megaloblatic anemias is megaloblastic erythropoesis in bone narrow, decreased
DNA synthesis and decrease in multiplication of cells. Red blood cells are bigger
than usual (megalocyte). It affects also platelets and granulocytes.

Pernicious anemia: Loss of B12 due to autoimmune gastritis is the cause.

Hematological: fatigue, exhaustion, dizziness, loss of air, arrhythmia, angious pain.
GIT: red tongue, anorexia and diarrhea. Neurological: demyelinisation of neurons
that can lead to death.
Deficit of folic acid: correlated with malnutrition or pregnancy when fetus has
increased needs for folic acid. Besides megaloblastic anemia decreased follates can
neurologically damage fetus. Lab diagnosis: megalocytes in blood, decrease in
platelets, reticulocytes and granulocytes.

83. Anemia due to hemoglobin disorder

ANEMIA DUE TO COMPLEX MECHANISM OF DEVELOPMENT

Anemias in this group don’t react on therapy but are corrected with removal of
primary disease: anemia in chronic diseases, uremia, endocrine diseases, liver
diseases. These anemias besides syderopenic anemias are most common in chronic
diseases. Usual infections that are followed by anemia are: TBC, pneumonia,
endocarditis, osteomyelitis and infections of urinary tract. Non infective diseases
followed by anemia: systemic lupus e., rheumatoid fever, rheumatoid arthritis.
Malignant diseases followed by anemia: Hodgkin, non Hodgkin, sarcomas and
lung carcinomas. There are three basic mechanisms: disorder in Fe metabolism,
decrease in red blood cell life span and insufficiency of bone narrow. All of these
are caused by proinflammatory cytokines (interleukine). Anemia is slight,
normocytic with hemoglobin value from 90-110g/l. Lower hemoglobin values will
lead to GIT bleeding so Fe and transferin will decrease also. Feritin increases
which is used to differ this type of anemia from syderopenic.

Anemia in chronic kidney insufficiency (CKI): Degree of anemia depends on

disease. There is low erythropoietin production. Red blood cells decrease due to
effect of uremic toxins on bone narrow. Life span of red blood cells is decreased.
Fe loss favors also development of anemia.

Anemia in endocrine disease: growth hormone, thyroxin, glucocorticoids and

testosterone affect production of hemoglobin directly (proliferation) or indirectly
(consumption of oxygen). Anemias are seen in hyperthyroidism, hypogonadism,
hypocorticism, etc.

ANEMIA DUE TO DISORDER IN HEMOGLOBIN SYNTHESIS

Two types of anemia belong to this group. In first type synthesis of one or more
globulin chains is decreased which represents a quantitative disorder that is called
talasemia while in second type there is structural change in these chains and
disorder here is called hemoglobinopathy.

Talasemia: autosomal recessive disease with many manifestations from benign

states in red blood cell morphology to life threatening anemias. Hemoglobin chains
are normal but production is decreased. Depending on type of chain we differ two
types of talasemia: alpha and beta. Alpha type is a hemolytic anemia, hypochromic
with increased target cells in blood. In beta type production of alpha chains is
bigger than total amount of gamma, delta and beta chains. Free alpha chains are
not stable and soluble so they accumulate in erythroblasts/cytes causing
permeability disorders. These red blood cells easily undergo phagocytosis. In
homozygote state anemia is heavy with bad prognosis while in heterozygote
talasemia is minor with slight micricytic hyperchromic anemia.

Hemoglobinopathy (Sickle cell anemia): usually caused in disorder of one globulin

chain (dot mutation). That form of hemoglobin can cause severe hemolytic anemia
or it can pass without any. First described hemoglobinopathy is sickle cell anemia
where glutamine is changed with valine in beta globulin chain so hemoglobin type
S is produced. Disease is caused by shape shift of red blood cells and hemoglobin
from oval to sickle shape. These sickle shaped red blood cells are not elastic as
usual so they can get stuck in capillaries. Also they aggregate more easily and they
can cause thrombosis. Basic symptoms are: hypoxia, infections and vasoocclusive
crisis.

84. Pathophyisiology of hemolytic anemia

Normal life span of red blood cells is about 120 days. Hemolytic anemia will
develop when bone narrow can’t correct increase in degradation of red blood cells.
In healthy individuals bone narrow can produce 6x more red blood cells with its
reserves. Hemolytic anemia is seen when red blood cell life span is about 20 days.
Causes of this can be acquired and hereditary and they are divided in two groups.
Anemia due to disorder in red blood cell is corpuscular while anemia due to
disorder outside red blood cell is extracorpuscular. Copruscular are also divided in
three groups more: disorder in membrane of red blood cell, enzymatic disorder in
production or usage of energy and metabolism of hemoglobin disorder.

Increased red blood cell degradation is followed by degradation of hemoglobin

which increases bilirubine. When non conjugated bilirubine overcomes functional
ability of liver for excretion then hyperbilirubinemia is seen. Released hemoglobin
binds to haptoglobin and oxydised hem binds to albumin and hemopexine. All of
this gets transported to liver where it is metabolized. When hemoglobin overcomes
haptoglobin and hemopexine then hemoglobinuri will occur which can lead to
kidney insufficiency. Compensatory reaction includes increase in RBC,
reticulocytes and erythroblasts.

Acute: headache, vomiting, pain in back, ribs and sometimes shock, hypotension,
tachypnea with anemia after several days

Chronic: depending on hemolysis degree. Latent: cholelithiasis and bile calculus

with slight anemia. In severe form: anemia with jaundice and splenomegaly. Lab:
increased bile pigments, decreased haptoglobine, hemosiderinuria,
hemoglobinuria.

CORPUSCULAR ANEMIA

Hereditary spherocytosis: hemolytic anemia due to disorder in membrane with

increase of red blood cells in number that are spherical in shape. Degradation of
RBC is increased in spleen. This is autosomal dominant disease characterized by
anemia, jaundice and increased spleen.

Deficit of 6-phosphate dehydrogenase: hereditary disease on x chromosome.

Metabolic disorders in red blood cells occur due to lack of energy and reductive
compounds which are needed for keeping Fe in fero form and protection of
proteins.

Deficit in piruvate kinase: autosomal recessive, no ATP – HEMOLYSIS

EXTRACORPUSCULAR

Imunne hemolytic anemia: increased degradation of red blood cells by antibodies

that is seen for example in blood transfusion when blood type is not corresponding.
Autoimmune hemolytic anemia with warm antibody: presence of IgG which react
with RhD antigen on erythrocytes that are active on normal body temperature.

Anemia from medication: kinines, tuberculostatics

Immunohemolytic anemia caused by cold agglutinins: consequence of

agglutination and lysis of red blood cells by act of IgM antibody which bind to red
blood cell membrane on temperatures that are lower than normal. It’s idiopathic in
infections

Paroxisimal hemoglobinuria on cold: most rare form. Caused by IgG that react
with P antigen on red blood cell membrane. Characterized by acute episodes of
intravascular hemolysis with abdominal pain and cyanosis.

85. Post hemorrhagic anemia

Normocytic normochromic anemia due to blood loss and clinical picture depends
on amount of blood that is lost. If 10-20 % is lost in steady state nothing will
happen while in working state tachycardia occurs with decrease in blood pressure.
Loss of 30% and more stimulates sympaticus and leads to thirst, dizziness,
tachycardia, sweat and hypotension in steady and working state. When more than
40% of blood is lost then minute volume drops down, blood pressure decreases,
puls increases, skin is wet, cold and loss of breathe. More than 50% is severe and it
leads to shock state with lactate acidosis and eventual death.

86. Polycythemia absolute and relative

Polycythemia is a disease where proportion of blood volume by red blood cells
increases. Hematocrit is bigger than 55%. It can be due to an increase in red blood
cells (absolute) and due to decrease in plasma content (relative).

Absolute: overproduction of cells may be due to primary process in bone narrow

(myeloproliferative) or it may be a reaction to low oxygen levels.
Primary: due to intrinsic factors for red blood cell precursosrs. Polycytemia vera or
rubra vera is a state when red blood cells are produved as an abnormality in bone
narrow with excessive platelets and white blood cells. By progression it can
transform in acute leukemia. In these patients erythropoietin is decreased, there is
affinity for thrombosis. Sypmptoms occur due to decreased blood flow in
microcirculation (ischemia). Headaches, angious pain, slight disturbances, etc.
Patinent is having a red cyanotic color, increased blood pressure and
splenomegaly. By laboratory red blood cells, hematocrit and hemoglobin increase.

Relative: erythrocytes are increased due to decreased blood plasma caused by loss
of body fluids (burns, dehydration, stress)

87. Quantitative disturbance in white blood cells

Myelopoesis – process of making red blood cells, granulocytes, monocytes and
platelets. These proceeses are done in hematopoietic blood organs: bone narrow,
thymus, lymph nodes and spleen. All blood cells start from pluripotent blood cell
(differentiation in whatever cell). By maturation they lose ability of differentiation
and that’s when they are called oligopotent and then unipotent stem cell. Stem cells
for gtanulocytes and lymphocytopoiesis by frowth factor matrurate in forms seen
in blood. First that can be recognized is myleoblast that passes to promyeloblast
and then myelocyte. Myelocyte by multiplication passes to metamyelocyte which
maturates in granulocyte.

Maturation and production of lymphocyte is done in thymus, spleen, lymph nodes,

etc. Stem cells in bone narrow differentiate in precursors of T and B lymphocytes.
B lymphocytes maturate in bone narrow and pass in blood while T go to thymus
and maturate there.

Process of granulocyte maturation from myeloblast to granulocyte lasts up to 10

days. In periphery blood one half adheres to endothelium (reserves that can be
activated by adrenaline) and migrate to tissues.

Monocyte lineage starts from CFU-M stem cell towards promonocyte in bone
narrow and then monocyte. When monocyte passes from periphery blood in tissue
then it’s called macrophage.
Based on origin and role white blood cells are divided in phagocytes (granulocytes,
monocytes) and immunocytes (lymphocytes, plasmocytes)

Phagocytes: provide phagocytosis (removal of MO, foreign antigen, etc.) while

lymphocytes have role in humoral and cellular immunity.

Disorders in white cell lineage can be qualitative, quantitative, morphological and

malignant.

QUANTITATIVE DISORDERS

Increase in number over 10x10^9 is lecucytosis while drop under 4x10^9 is

leucopenia. They usually occur due to quantitative disorder in neutrophilic
granulocytes.

Neutrophilia: Increase of n. granulocytes over 7x10^9. When it passes 30x10^9

then we talk about leukomoid reaction since there is a lot of young cells from
granulocytic lineage. Pseudoneutrophilia occurs die to passage of marginal
neutrophils in circulation under influence of adrenaline, stress or cold. Neutrophilia
can be congenital and acquired.

Neutropenia: represents a drop in neutrophils inder 1.5x10^9 and when under

0.5x10^9 then it’s called agranulocytosis (increased risk for infection if it’s under
1x10^9)

Mechanism of development: low production due to decrease in stem cells in bone

narrow, non effective granulocytopoieses, destruction by inflammations or
accumulation on periphery.

Hereditary form is rare. Most common is cyclic neutropenia due to use of

cytostatics or immunosuppressive therapy in malignant disease or autoimmune
disease treatment.

Eosinophilia: number is over 0.7x10^9. Expressed eosinophilia is seen in

trichinella infection, allergies to drugs, systemic diseases of connective tissue and
malignancies.
Basophilia: Basophils in blood or periphery tissue (mastocytes) contain granules
that are released in reaction of hypersensitivity. Numver is over 0.2x10^9. It’s seen
in infections, urticaria, rheumatoid arthritis and malignancies.

Monocytes: more than 0.9x10^9 is seen in infection and it’s called monocyotisis.
Monocytopenia is seen in aplastic anemias.

88. Qualitative disorders in granulocytes

These disorders can be divided in morphological and functional.

MORPHOLOGICAL: it can affect nuclei, cytoplasm or size.

Macropolycytosis: granulocytes are bigger than normal with normal function. It

can be congenital and acquired (b12 defficiency)

Pelger Huet is benign hereditary disorder where nuclei is round or it has 2

segments.

Aurel poles: seen in cytoplasm of myeloblasts in acute leukemia and toxic

granulation in neutrophils during infections.

FUNCTIONAL

They can occur due to deficit in complement, autoimmune disease, hemodialysis,

decreased phagocyte function, decreased movements or due to deficit in
myeloperoxidase.

Most common is deficit in myeloperoxidase which is autosomal recessive and is

isolated so it’s not affecting defense of organism too much but when it’s followed
with other diseases like diabetes then patients get easily infected by fungi. Chronic
granulomatous disease: decrease in microcidal functions in neutrophils dependant
on oxygen.\
 89. Malignant diseases of white blood cell line
Leukemias are clone malignancies of hematopoietic stem cells which start in
proliferation of malignant clone in bone narrow with dissemination in blood,
spleen, lymph nodes, etc. It’s connected to genetic factors, radiation, etc.

Acquired diseases of stem cell like myelodysplasia and myoproliferative diseases

can evolve in acute leukemia.

Leukemia can be lymphoblastic, myeloblatic, acute and chronic.

Acute is characterized by presence of non differentiated or non maturated cells –

leukemic blasts, and in chronic maturated but with inappropriate function.

ACUTE: there is a stop in differentiation. Malignant cells are acculumated in bone

narrow so they compress normal hematopoiesis which leads to anemia, infections
and bleeding. Leukemic cells inhibit hematopoiesis by humoral and cellular
mechanisms. They first proliferate in bone narrow, pass in blood and they can
infiltrate many organs. There is French – American – British classification where
acute lymphoblastic leukemia has 3 types and acute myeloblastic 8 types.

CHRONIC GRANULOCYTIC LEUKEMIA: group of myeloproliferative diseases

characterized by increased production of blood cells. This is a clone malignant
disease of hematopoietic stem cell with characteristic genetic change that is called
Philadelphia of chromosomes. In this Philadelphia during translocation a fusion
gene is produced. This gene codes protein synthesis which has activity of tyrosine
kinase for proliferation. Genetic stability (non) of malignant clone leads to
transformation of disease from chronic type to acute type and then we can see also
some other genetic abnormalities besides Philadelphia. Disease starts with chronic
phase – acceleration – transformation (acute type). In chronic phase number of
leukocytes increases (over 200x10^9), First symptoms are fatigue, increased
sweating and temperature, decrease in body weight. Depending on platelets some
bleeding can be seen. Increased concentration of urine acids leads to arthritis and
damage of nephrons. In periphery blood leukocytosis, thrombocytosis,
granulocytes present with some non maturated forms, increased basophils and
neutrophils.
 90. Neoplasms of lymphocyte system
Lymphoproliferative or immunoproliferative disease that represents a stop in
differentiation at some stages (clonic proliferation) . Clinically it can manifest as
leukemia, malignant lymphomas, syndrome of immunoglobulin producing cell,
etc. These neoplasms are classified in leukemia and lymphomas.

Leukiemia is a disorder where bone narrow is infiltrated together with blood and
lymphoma is a disorder where besides these also lymphoid organs are affected.

Chronic lymphocyte leukemia: lymphocyte infiltration of bone narrow and blood.

It occurs due to malignant transformation of B lymphocytes. Basic disorder is
clonic expansion of pathologically changed lymphocytes with saved maturation but
apoptotic disorder. In same time normal lymphocytes are disordered which leads to
hypogamaglobulinemia. In clinical picture there is: anemia, increased size of
spleen and lymph nodes, infections and in blood lymphocytosis is seen. By
morphology we differ prolymphocytic leukemia (aggressive) and tricholeukemia
(rare, fibrosis of bone narrow, pancytopenia).

Lymphomas: malignant transformation of lymphocytes and histiocytes. Seen in

lymph nodes. Basic are Hodgkin and non Hodgkin

Non Hodkgin: heterogeneous group of lymphoproliferative disorders with malign

transformation of lymphocytes in lymph nodes. Cause is not known. It’s seen more
in persons with congenital and acquired immunodeficiencies, autoimmunities, etc.
Helicobacter Pylori is correlated with gastric lymohoma. Clinical symotosma are
compressive action of big lymph nodes on GIT and urinary tract. Infiltration of
bone narrow leads to insufficiency of myelopoesis with characteristic symptoms of
anemia, thrombocytopenia and granulocytopenia

Hodkgin: malignant neoplasm of lymphoid tissue where malignant transformed are

Reed-Sternberg cells. Etiology is not known. Increased risk s seen when infections
with Epstein Barr virus or HIV occur. There are 4 types: lymphocytic
predomination, nodular sclerosis, mixed cellularity and lymphocyte depletion. In
patients with Hodgkin function of T lymphocyte is damaged and tuberculin probe
is negative. Disease starts without pain and it’s mostly asymptomatic in the
beginning.
 91. Disorders of plasma cells
Disorders in plasma cells represent a terminal stadium in B lymphocyte maturation
characterized by disorder in immunoglobuline synthesis. They can be dividied in
reactive and neoplastic disorders. Reactive represent an answer to antigen
(polyclonic hypergamaglob.) while neoplastic represent monoclonic immunoglob.
production (M component).

Multiple myeloma: Most common neoplastic disorder affecting plasma cells due to
clone proliferation in bone narrow. These cells secrete M protein and prvoke
dissolution of bone tissue. Etiology is not known. In affected bones osteoclastic
activity is increased which increases calcium levels in blood and risk for
pathologic fractures. At the same time lower immunoglobulins will result in
decreased immunity. Most common symtoms are bone disorders, anemia,
leucopenia and thrombocytopenia. Concetration of creatinine and ureic acid
increases.

92. Disorder in hemostatic system.

Hemoostatic system is involved in hemostasis by many factors where the most
important is prevention of bleeding and thrombus formation. It is involved in
inflammations, wound healing, reproduction, etc. Basic components of hemostatic
system are blood vessels, platelets and plasma proteins that are divided in three
groups (coag factor, inhibitors, fibrinolytic factor.) Activation of these components
is localized on injury site. That’s why all components are found in circulation as
non active components. Activation occurs only for factor that is needed in given
phase and when it finishes its action is inhibited so next factor can be activated (all
in order to form a blood clot). Mechanism: when damage occurs first seen is
vasoconstriction is seen. Platelets are adhering to endothelium so they can
aggregatie and express coagulation. Blood clot is localized on damage of blood
vessel without any expansions to healthy endothelium. In blood clot platelets, RBC
and WBC are present. Coagulation represents a series of reactions where non
active form of coagulation constituents are transformed to active forms by
proteoplytic degradation (prothtombine – thrombine – fibrin). New amount of
fibrin that is formed is enough to exchange diluted fibrin in non dilutive fibrin
fivers (prophylaction). Many inhibiting factors stop coagulation where most
significant is inactivator of coagulation and inactivator of thrombine-
antithrombine. Active enzyme that has central role in fibrinolytic system is plasmin
that is formed from plasminogen.

93. Hemorrhagic syndrome

Bleeding can occur due to abnormality in morphology or function in blood vessels,
qualitative disorder in platelets, disorder in coagulation or fibrinolysis. Bleeding in
skin is called purpura, from nose – epistaxis, gingivorrhea, menorrhea (uterus),
GIT (melena), etc. Hemorrhagies can be congenital or acquired and they are
divided in 3 groups: vascular syndrome, thrombocytopathies and coagulopathies

Lab tests are showing that bleeding time increased, number of platelets increase
and prothrombin time increases.

Vascular hemorrhagic syndrome: group of disorders usually manifested with

bleeding in skin and mucosa. Bleeding occurs due to increase in permeability of
blood vessels, decreased resistance o blood vessels and inability of blood vessel to
contract after injuty. They can be congenital and acquired. Congenital is a
consequence of malsynthesis of elastic fibers or disorder in blood vessel
morphology. Acquired occur due to damage of structure, function and support of
blood vessel walls.

Congenital hemorrhagic teleangiectasia (Mb Reudo Osler Weber): Most common

hereditary disorder of blood vessel wall that is autosomal dominant. Basic
characteristic is widening of small blood vessels, red or purple color that is lost on
pressure. Seen in skin, mucosa and other organs. By aging bleeding increases.
Bleeding is usually occult and if it persists it can lead to syderopenic anemia.
Bleeding time and other tests are normal.

Acquired vascular purpura: due to malfunction in synthesis of elastic fivers or

accumulation of pathologic proteins in wall of blood vessel.

Vasculitis: heterogeneous group of diseases that are characterized with

inflammatory and necrotic changes in blood vessel walls.
Allergic anaphilactoid purpura: most common in type in incidence and its
characterized by palpable purpura. Localised on lower limbs usually, abdominal
pain and glomerulonephritis is seen. Disease formation is related to infection,
insect bite, drugs, etc.

Thrombocytopathies: Platelets are smallest blood cells and their number is 150-
450x10^9. They are produced in bone narrow from megakariocytes and circulate in
periphery blood around 8-9 days. Disorder can be expressed as thrombocytopenia
and thrombocytosis.

Thrombocytopenia: by mechanism it can occur due to low production, increased

degradation or sequestration. Low production occurs in states where bone narrow
is aplastic (Wiscott Oldrich – congenital). Increased degradation occurs due to
antibody formation against platelet membrane so they are removed by
phagocytosis. Life span of platelets decreases and there is an increase of
megakariocytes in bone narrow. Acute form due to this occurs in kids for example
after infection and it’s manifested as petechial bleeding. Chronic form is
autoimmune and is characterized by petechia, epistaxis, etc.

Coagulopathies: qualitative disorders that can be congenital or acquired. Genetic

defects in morphology of glycoprotein which damages function and adhesion.
Bernard Sullie is hereditary disease that decreases platelets. Clinically mucosal
bleeding is seen and increased time of coag. By histology gigantic platelets are
seen. Acquired is seen when patients use medication for preventive measures for
thrombosis.

94. Disorder in blood coagulation

Occurs due to lack or decreased activity of one or more factors of coagulation.
They can be acquired and congenital. Congenital usually occurs due to decreased
synthesis and it’s expressed as a lack of functional activity while acquired results
in lack of more factors.

Hemophilia A: lack of factor of coagulation FVIII which affects males while

females are carriers. Lack of this factor decreases activation of FX so there is no
thrombine – fibrin – blood clot. In severe forms where FVIII is under 1% present
bleeding occurs without any trauma.

Hemophilia B: lack of factor FIX and its 7x more rare than A type.

Von Willenbradt: most common with different degree of damage. Hereogeneous

group of disorders disturb VWF which is needed for adhesion of platelets and to
transport FVIII.

Fibrinogen (genetic disorder): occurs due to decreased synthesis or changed

function. Afibrinogenemia.

95. Acquired disorders of coagulation

Usually they occur from liver diseases, decrease in vit. K or disorders that activate
fibrinolytic system too much.

Disorder in liver diseases occurs commonly since liver is needed for production
and removal of coagulation factors. Bleeding is usually seen due to anatomical
damage and usually it’s caused from portal hypertension.

Vit. K is used for post ribosomal carboxilation of glutamine in molecules of

vitamin K dependant factors so they can bind to Ca and phospholipids on surface
of platelets. In obstructive biliary disease vitamin k cant be used so coagulative
factors decrease and that leads to bleeding in GIT and urinary tracts. Oral
anticoagulants influence vitamin k decrease when used in high doses and it can
lead to bleeding in cns.

Diseminated intravascular coagulation: DIC is a complex clinical syndrome that is

characterized by intravascular activation of coagulation resulting in fibrin
production and microthrombosis so all factors of hemostasis are used which leads
to hemorrhagic syndrome. It’s usually seen in pregnancy complications or sepsis.
Endothelial damage is the trigger when we talk about sepsis (endotoxins).
Endotoxins provoke release of cytokines which release tissue factor and VWF
from epithelial cells. At the same time they suppress degradation of fibrin which
all together can lead to thrombosis. During thrombus formation all factors are used
up so hemorrhagia occurs. In acute DIC hemorrhagic syndrome is expressed: seen
after venicpuncture, surgical wounds, recurrent hematomas, epistaxis, etc. GIT
bleeding here can lead to shock. Microthrombosis can affect most organs and cause
ischemia with consequences. In chronic type bleeding i seen in skin and mucosa.

Primary fibrinogenolysis: occurs due to increae activity of plasminogen where

fibrin is degraded. Herediatary is rare but seen due to decrease in alpha 2
antitripsin and it’s autosomal recessive. Acquired:occurs due to release of tissue
activators for plasminogen in big amounts. It’s seen in malignant tumors, after
surgery of prostate, trauma, cirrhosis, etc. It can occur also due to usage of
medication. Clinically: bleeding in GIT, UT, epistaxis, hematomas, etc.

96. Thromboembolism
Intravascular formation of blood clot is thrombosis. By blood vessels that is
affected it can be venous and arterial. Arterial is seen in places of increased blood
flow while venous is seen in places of slow blood flow. By increase of thrombus
size obstruction can occur. In arterial obstruction ischemia and necrosis of organ
can occur while in venous it will disorder blood flow towards heart. Part of
thrombus can rip off and by process of embolism go in pulmonary circulation or
distal part of arterial vessels causing necrosis and ischemia. Mechanism of
development includes damage of one or more components in Virchovi trias (wall
of blood vessel, blood flow, content).

Blood vessel wall damage: contact of platelets with subendothelial structures is

provided so there is adhesion and aggregation of platelets. Mostly it’s seen in
arterial thrombosis.

Venous thromboembolic disorder: thrombosis in veins. Usually in deep leg veins

that is seen as swelling of legs that is painful and cyanotic. Thromboembolism of
pulmonary artery can occur from thrombus of deep leg vein.
 97. Disorders in hunger and appetite
Hunger is a non pleasant feeling of gastric contractions and other manifestations
from sympatic nervous system produced by hypoglycemia. Person who didn’t take
any food for several hours will fell hunger contractions. Contractions make us feel
inder tension and sometimes we can experience trembling. Appetite is a wish for
certain food while hunger represents the actual need. After we take food we feel
good and that our need is fulfilled. Feeling of hunger is regulated by group of
nerve centres in hypothalamus. Lateral is for hunger and ventromedial is for
satiation. On these centers many factors can have effect. Hunger centre receives
information from fat about reserves which are used for long term regulation of
energetic balance. Short term impulses activate hunger centre only when GIT is
ready to take food.

ANOREXIA: loss of appetite is hyprexia while anorexia is total lack of it and it’s
seen in all disorders of digestive tract which act inhibitory on hunger centre so
desire for food is decreased. Seen in acute inflammations of GIT, obstructive
diseases, carcinomas in stomach (rare symptom: disgusted by meat). It can be seen
also in many other diseases and in all febrile states so it increases negative balance.
In congestive heart failure due to edema of red mucosa there is disorder in
secretion of intestinal jucies which inhibits hunger centre. Liver diseases also cause
anorexia due to metabolic disorders. Many endocrine disorders and hematological
also are followed by anorexia. Malignant due to toxic action on food centre also
cause it.

Panorexia: psychological disorder where people eat things that are not supposed to
be eaten.

Most important consequence of anorexia is decreased BMI with metabolic and

morphological changes

Polyfagia: increased will for food intake seen in diabetes and hypothyroidism for
example.
 98. Etiopathogenesis of nausea and vomiting
These are common disorders in GIT diseases.

Vomiting (emesis): act of releasing GIT content when GIT is over stimulated,
congested or spread. Impulse is going from GIT via vagal and sympatic nervous
fibers to bilateral centre in medulla oblongata. When this centre is stimulated
coordinated motoic actions are produced which let vomiting happen. These
impulses from vomiting centre to diaphragm are transferred via n. frenicus. Spinal
nerves transfer impulses to abdomen and to larynx, pharynx and esophagus
impulses come via vagus nerve. Act of vomiting starts with lift of hyoid bone and
larynx so cricoesopharingeal sphincter is open, glottis is closed, soft palate raised
and choanas are closed so there is no aspiration. After one heavy contraction of
diaphragm and abdomen occurs which will raise intergastric pressure and as a
consequence of that raise content will be expelled.

Nausea: is a unpleasant feeling that usually comes before vomiting so we can

consciously feel stimulation of vomiting centre. Nausea is sometimes caused by
spread or irritation of duodenum so it contracts and content goes back to stomach.
Vegetative system is stimulated so we are in pain, sweaty, salivating, decreased
heart rate which leads to vomiting. Consistent vomiting can lead to loss of liquid
and alkalosis. Muscle weakness, hypotension, etc.

99. Etiopathogenesis of abdominal pain

Abdominal pain is most common sign of GIT disease cause by many factors. This
pain cant be used for localization of pain since it’s not always where the affected
organ is. Stomach organs contain mechanoreceptors (spread) and nocireceptors
(pain) which are not so well arranged. Parenchyma is almost not sensitive while
peritoneum, capsules and cavities of organs are. Sensory stimulation results in
visceral pain. Parietal parts by many receptors provoke surface pain. Between
visceral and parietal pain there is one difference that localized damage in inner
organs rarely causes pain.
Causes: every stimuli for nervous fibers in bigger part of stomach causes visceral
pain. Ischemia causes pain with acid metabolites accumulation or bradykinine that
stimulates nerve endings. In people ulcer pain from HCl chemical irritation is
present. Strongest pain in abdomen occurs due to cramps of stomach musculature
caused by decreased blood flow in cramped muscles. Commonly pain is
rhythmical with increasing intensity and then it stops. Rhythmical cycle /
rhythmical contraction is called colic. This kind of pain is seen in gastroenteritis,
bile sack diseases, obstipation, etc. Increased load of stomach cavity spreads it or it
provokes edema with spread of fibrous capsule that causes pain. This spreading
can compress blood vessels.

Irradioation of pain: one characteristic is irradiation so visceral is manifested as

surface pain caused by two possibilities: parietal surfaces are innervated with
spinal nerve fibers which go from surface inward. When pathological process
stimulates there is pain of parietal wall in visceral cavity that is stromg and
localized above organ. Seconda case is when person feels pain in another part
away from affected tissue (part of visceral pain transferred one part of pain as
parietal). There are several reasons why abdominal pain is hard to localize. First
inner organs are not well introduced to sensory cortex as skin. Plus there are two
types. If visceral is over stimulated that stimuli will spread also to some neurons
for pain from the skin only.

100. Etiopathogenesis of GIT bleeding

Bleeding from GIT is one of advisory signs for disease of GIT. Bleeding can occur
from any part of tract with blood going in lumen where it will finish in feces or
emetic content. Blood in emesis is called hematoemesis and blood in stool is called
melena. Both suggest that bleeding is from upper part of GIT. Blood in emesis by
color depends on HCl. Cause of hematoemesis is always proximal from duodenum.
Bleeding that causes hematoemesis causes melena all the times. Stool in melena is
black, sticky and has characteristic smell. For melena to be seen 50-60ml of blood
which means that there is also a possibility for our patient to bleed out. Under 50ml
melena is difficult to determine macroscopically so occult bleeding tests are done.
If blood is black (contact with HCL – hemoglobin – chlorhematine) then it’s
proximally from duodenum. It it’s not digeested (red) then it’s distally.
Macroscopically if it is from lower intestine then blood is mixed with stool. If its
from rectum then it will be surrounded (envelope) by blood. Causes: in upper part
usually ulces and cancer whule in lower inflammations and cancer of colon or
rectum. If bleeding is massive then maybe its caused by rupture of venous vessel.
From upper part bleeding can come due to drugs that damage mucosa, ulcer,
ulcerations, alcohol, etc. Lower: hemorrhoids, inflammations, carcinoma.

101. Disorder in esophagus and stomach motility

Digestive tract disorders can be motor, secretive and digestive.

Motor: muscles in digestive tube are longitudinal in outer part and circular in inner
made from smooth muscles. These muscles provide food mixing and movement
towards rectum. Muscles of pharynx and 1/3 esophagus are striated and they are
inervated by glossopharingeal and vagus nerves so act of swallowing is voluntary.
Disorders in motility: Main motoric action of esophagus is swallowing that starts
with voluntary phase where tongue lifts toward soft palate so nasopharynx is
closed and food bolus goes towards pharynx and it activates oropharingeal
receptors so reflexive part of swallowing can begin (laryngeal/esophageal). Bolus
passage from primary esophageal factor is acused by first peristaltic move in
pharynx which activates opening of esophageal sphincter so it can enter stomach
(lasts around 15 secs).

Dysphagia is used to describe difficulties in swallowing, aphagia – impossibility to

swallow and oddinophagia describes painful swallowing. Dysphagia occurs due to
weak contractions or non coordinated muscle work. It can be acute and chronic
which leads to malnutrition, loss of body weight and aspiration of foreign body.

There are several MOTOR DISORDERS IN ESOPHAGUS:

ACHALASIA is a diseases of unknown etiology that is characterized by functional

obstruction on esophagogastric junction level caused by increased tonus of cardial
sphincter, loss of its relaxation or loss of peristalsis while swallowing. It causes
dysphagia, retrosternal pain and loss of body weight. Food stops in esophagus and
it spreads it. Primary: damage of cells/lack from myenteric plexus. Secondaru:
esophageal nerves damage by malignant infiltration.

REFLUX OF GASTRIC CONTENT represents a retrieval of acidic content to

esophagus that is characterized by heartburn. It can occur due to increase in gastric
volume, increased abdominal pressure or decreased tonus of esophageal sphincter.
Persistant reflux leads to inflammation of mucosa.

HIATUS HERNIA is a disease where one part of stomach or whole portion comes
through esophageal opening on diaphragm. It can occur in phases of work or it can
happen in certain positioning. Also it can be fixed. Clinically abdominal pressure is
increased, dysphagia, pain and heartburn. All of this can lead to complications such
as bleeding, clenching of hernia, valvulus.

MOTOR DISORDERS OF STOMACH

Stomach has a role in mixing of food and its transfer towards duodenum. This
process can be disordered as gastroptosis, hypomotility, hypermotility, vomiting,
hypotony or hypertony.

Gastroptosis: occurs in lower stomach where food falls in lowest part of prolonged
gizzard (gaster, stomach) so peristalsis and emptying are disordered.

Hypermotility is increased motoric action by visceral reflex mechanism and

hypomotility occurs due to decreased peristaltic waves and emptying which is seen
in gastritis or gizzard atrophy. Mechanical cause of this disorder is ulcer or some
malignancy.

Gastroparesis is a cause of digestive problems in diabetic patients: hypomotility,

dilation, pyloric spasm due to vegetative neuropathy.

Acute dilation: loss of tonus and emptying due to surgery, increased food intake.

Dumping syndrome represent symptoms after food intake caused by fast passage
of it through gizzard. Seen in resection of gizzard or from food that causes
increased motility. This syndrome has 2 forms:
*early: after fatty food that is hyperosmolar. Dystension of intestines is seen which
increases by fluid coming from extracellular parts to lumen. Hypovolemy is seen,
hypotension, tachycardia and possible collapse.

*late: occurs 2 hours after meal that is rich in carbohydrates due to fast absorption
of glucose. Hyperglycemia, hyperkaliemia.

102. Patophysiology of diarrhea

Diarrhea represents a frequent defecation with liquid stool in increased amount.
Defecation usually occurs 1-3 times a day (normal). Food has a major role in
diarrhea manifestations. By cause it can be acute and chronic.

Acute: occurs due to infections or medication. Many microorganisms can cause

diarrhea like shigella, salmonella, Escherichia Coli, clostridium, etc. Diarrhea by
vibrion infections or colera can cause death. Typical clinical picture: nausea,
vomiting, headache, liquid stool and increase in temperature. Appereance of stool
depends on cause of diarrhea. Those who produce strong toxins and stimulate
peristalsis will result in liquid stool in big amount that is followed by headache.
Liquid stool without nausea and headache is characteristic for cause that enter
epithelia without inflammation like some viruses. Shigella and salmonella cause
inflammation, fever, pain and stool that is liquid with melena. Biggest
complication of acute is development of isotonic dehydration with hypokaliemia
and acidosis due to loss of water and bicarbonates. Therapy in this case is
rehydration with antibiotics application.

Chronic occurs several tymes a day with semi liquid stool consistency. Mostly is a
consequence of other diseases. Based on their development they are classified in
inflammatory, osmotic, secreting, motor and pseudo.

INFLAMMATORY is seen in chronic inflammations which irritate mucosa and

fasten peristalsis. Usually is a part of idiopathic inflammatory disease like Crohn.
Diarrhea is followed by arthritis, skin changes, vascular uveitis, etc. It can occur in
some carcinoma, clostridim, HIV, etc.
OSMOTIC is seen when in intestinal lumen there is non digested or non absorbed
food which by osmotic action attracts water from blood vessels and tissue so much
that it overcomes capacity of colon for water reabsorption so stool is liquid. In this
stool we can find non digested food. It’s greasy and it has a characteristic smell.
Usually it’s seen in pancreatic disorders or gluten sensitivity.

SECRETING produces a big amount of stool with increased electrolytes and water
that is not correlated to food intake but hormones that stimulate intestinal juices or
carcinoma that secrete vasoactive substances.

MOTORIC is seen due to nervous regulation of intestinal motility (irritable colon

syndrome). Increased excitability of colon musculature stimulates
cholecystokinines and cholinergics. It can occur in several GIT levels (colon,
gizzard, duodenum, small intestines) and it’s followed by somatic changes (pain,
bloating, defecation problems)

PSEUDO is seen due to laxatives usage

Chronic diarrhea leads to decreased body weight, dehydration, malabsorption, etc.

103. Patophysiology if opstipation

Opstipation or constipation represents difficulties in defecation. Usually all stool
amount is in colon and sigma while there is no any in rectum. Peristalsis moves
stool to rectum so defecation is stimulated. Massive peristalsis in colon usually
occurs after first intake of food for htat day (food-gizzard-gastrocholic reflex).
When content passes sigmoid colon fills up ampulla which activates defecational
reflex. Defecation reflex starts with spread of rectal wall which emits afferent
signals towards sacral centre in spinal cord and by parasympatics goes back to
colon, sigma, rectum and anus. By mechanism of development constipation can be
functional and organic. Organic – barrier for stool passage that is located usually in
anorectal part. Fucntional can be protogenic, atonic and spastic.

Protogenic: there is a shut down in defecation reflex. Inner sphincter pushes feces
and activates outer sphincter. If voluntary its closure is prolonged then defecating
reflex shuts down until next amount of feces comes. If this kind of inhibition is
done in a prolonged manner it can shut down the reflex completely. Serious
constipation is caused by psychological factors (stress, fear, culture), pain in anal
tissues, hemorrhoids, damaged mucosa, etc. Organically is seen in neoplasms, Mb.
Crohn and tuberculosis of intestines.

Atonic: rare and weak peristalsis which is inhibited due to decreased food intake,
psychological factors like depression, hypothyreoidism, opioids, etc. In
hyperparathyroidism there is expressed atonia of colon musculature due to
hypercalcemia aswell in hypothyreoidism and hypokaliemia. It’s seen in elderly,
females, in cahexia, etc. and it’s not followed by expressive symptoms. There is an
increase in colon caliber.

Spastic occurs due to spasm from emotional or psychologic factors in younger,

nervous persons. It’s followed by intestinal cramps. Hereditary colonal amyliosis
leads to accumulation of feces and constipation (empty ampulla). Opiates also can
cause spasm in sigmoid colon so during physical check up in left part of stomach
descending part of colon is hard and palpable (decrease in caliber and peristalsis)

Organic: by organic barrier for food passage is present. Lumen is decreased by

expansive processes (inflammation, neoplasm). Mb. Crohn, carcinoma, lymphoma.

Consequences of constipation:

When constipation is prolonged it can provide reabsorbtion of toxins, products of

rotting which leads to headache, tension, increased body temperature, decreased
body weight. In extreme cases colon due to dilation can perforate – sepsis.

104. Patophysiology of illeus

Acute obstruction of intestines is called illeus and it’s a disorder in motorics and
passage that stops further movements of intestinal content. These obstructions can
be divided in mechanic, functional.

Mechanic/obstructive: decreased diameter due to many intralumenar, intraural or

extralumenar factors that lead to obstructions that can be obturational and
strangulative.
Obturational is accompanied by big loss of water and electrolytes and strangulative
occurs due to decreased blood flow in mural part of intestines.

Obturational: intraluminar (big bile calculus in lumen, polyp), intramural (atresion,

stenosis, tumor), extraluminar which are the biggest by the way (adhesions of
peritoneum from surgery, tumor, infections).

Dystension of intestine increases intralumenal pressure above the barrier.

Dystension occurs due to increased gas/liqudim with increased peristalsis in
beginning to confront blockage. Then antiperistalsis occurs (emesis). Intestinal
wall is swollen and water and electrolytes are excreted in lumen. Loss of liquid is
increased (up to 8l) and it leads to hemodynamic disorders. Vomiting leads to
dehydration and loss of electrolytes. Decreased circulation leads to ischemia in
intestinal wall, gangrene and eventual perforation that can cause death.

Strangulative illeus has 3 forms:

Valvulus: torsion of one segment in small intestine that causes obstruction by

anatomical anomalies.

Incarceration: when villi with mesenterium pass through opening of abdominal

hernia and get stuck there

Invagination: one segment with mesenteric part is in lumen. Seen in kids.

Functional: there is no obstruction but changes in peristalsis.

Paralytic: no peristalsis due to neuromechanical disorders so there is no movement

of content.

Spastic is rare and it’s seen in Pb poisoning, purpura, mechanical stimulations, etc.
Peristalsis is decreased in one segment.
 105. Disorders in secretion
In digestive tube there are many glands for digestion. In mouth amylase is
produced and in stomach HCl and pepsine.

Mouth: saliva (parotid, buccal, sublingual gland) is a major factor in oral

homeostasis. Carbohydrate digestion starts in mouth by ptyaline or alpha amylase.
Food is wet, soft so it can be more easily digested in stomach. Other important role
is antimicrobial action (washing). It contains also 2 more enzymes: canicreine and
antigens of blood group. Aptyalinism is decrease in salivation which leads to
xerostomia (acute, chronic). Acute occurs due to dehydration, infection of salivary
glands or increased tonus of sympaticus. Chronic leads to infection and caries
development.

Syaloreia is increased salivation that occurs due to increased tonus of

parasympaticus, inflammation or it follows other diseases like Parkinson.

DISORDER IN GASTRIC SECRETION

Gastric juice is produced in amount of 1500-3000ml a day. Main constituents are

water, HCl, electrolytes, enzymes, mucus and intrinsic factor.

HCl is most important (parietal cells) and it produces acidic pH. It has bactericidal
effect and it degrades pepsinogen to pepsine so proteins can be digested. HCl is
formed from parietal cells mostly in fundus and body of gizzard. Beginning of
secretion starts with synthesis of HCO3 from CO2. HCO3 gives H ions and
bicarbonate. H ions in lumen and bicarbonates in blood exchange for Cl. In
membrane of parietal cells we have muscarinic, histaminic and gastirn receptors.
Vagus nerve is main stimuli for secretion directly from acetyl choline that binds to
muscarinic receptors.

Gastrin cells give gastrine which goes in blood in form of amino acids. By blood
they come to all parts of gastric mucosa so they bind to G receptros of parietal
cells.

Pepsine is formed from chief cells as pepsinogen which is later transformed to

active form with HCl. Stimulation of pepsine and HCl secretion is done by
gastrine. Main way for HCl secretion cant be determined because acetyl choline
and histamine are main stimulants in cephalic phase while gastrin is in gastric and
duodenal phase. Strongest secretion occurs when all 3 stimulants act together.
Decrease of HCl can be achieved by blocking of receptors (medication).

Disorders in secretion of hydrochloric acid can be in range of decreased or

increased secretion.

In achlorihydria there is a disorder in digestion with possible bacteria

multiplication that leads to diarrhea. This is a consequence of gizzard atrophy
(gastritis)

Hyperchlorhydrioa occurs usually due to vagal stimulation with increase in number

of parietal cells or due to gastrin secreting tumors. Increased Cl goes in duodenum
and causes ulcers.

106. Eiology and pathogenesis of ulcer

Peptic ulcer is erosion of gastric or duodenal mucosa caused by HCl and pepsin.
It’s a result in disbalance of secretion between HCl and defensive mechansimsm in
mucosa. Concetration of HCl in gastric juice is 160 mEq/l and pH is 1.0 so with
pepsine is enough to tear gastric and duodenal mucosa. Mucus, alkaline juice,
saliva, duodenal juice are there to protect. So when this is disbalanced ulcer will
form.

Gastric secretion has 3 phases. Cephalic during hunger and it stimulates vagus
nerve so HCl is produced. Gastric is humoral/neural. Food content stimulates
vagus and G cells. Intestinal is seen 2-3 h after food intake. When food passes HCl
secretion is inhibited (humoral) byfat, carbohydrates, salt. Prolonged Hcl secretion
is seen due to mechanisms that stimulate vagus nerve.

Mechanisms of defense: mucus – glycoprotein from cells in epithelia. Mucus

comes in 2 forms: thin layer of stable non dilutional gel on mucosa, diluted with
intralumenal liquid that is above thin layer.

In 95% of gastric and 80% duodenal ulcers Helicobacter Pylori is seen that
produces enzyme urease so urea is formed that dissolves mucus, neutralizes HCl
and adjusts pH for its survival. Amonia-inflammation-increase in HCl-ulcer. For
ulcer however more factors are needed: decreased defensive mechanisms,
decreased circulation in mucosa, irritation, infection, etc.

107. Acute and chronic pancreatitis

Pancreas is a main secreting gland which secretes about 1.5-3l of alkaline liquid
containing 20 enzymes for food digestion.

Duodenal mucosa secretes secretin and cholecystokinine which acts as a stimulator

for pancreatic juice secretion. HCl-ecretin-pancreas-juice. Since p. juice is full of
bicarbonates it neutralizes HCl and brings pH to 8 which is optimal for pancreatic
enzymes. Fatty acids stimulate cholecystokinine-pancreas-enzymes. Most
important enzymes are: amylase, phosphoriylase, lipase, cholesterol esterase,
tripsine, hemotripsine, elastase, carboxypeptidase and aminopeptidase.

Secretion decreases in acute/chronic pancreatitis and cystic fibrosis of pancreas.

Acute starts by tripsine activation which by chain reaction activates others. 2 basic
causes are cholelithiasis and alcoholism. In biliar colic there is spasm of sphincter
and in alcoholism inflammation of duodenum leads to edema, obstruction and
decreased juice secretion.

With secretion of p. juice by secretin pressure in pancreatic canals increases which

leads to edema with symptoms. If pressure increases more then walls will crack
that activate tripsin and others. Elastase damages blood vessels which can lead to
bleeding. Lipase decreases fat tissue on surface of pancreas. Posphorylase damages
membranes of cells, lecithin is formed which has toxic action. Calicreine activates
bradykinine which provokes vasodilation and can lead to shock

Dg. of acute pancreatitis is one of the most dangerous states in abdominal

pathology. Enzymes digest pancreas with bleeding – abdominal cavity – septic
inflammation. In blood of patient: leukocytosis, hyperglycemia, hypocalcemia,
coagulation system activity. Only good part is that enzymes are easily found in
blood so it’s easy to diagnose.

Chronic: permanent inflammation with parenchimal damage and fibrosis of it.

Characteristic is also calcification. By etiology same as acute so chronic is actually
a repetition of acute episodes. Decrease in endo and egso pancreas leads to
malabsorption, maldigestion, insulin depending diabetes.

Cystic fibrosis of pancreas is auto recessive where salivary glands, bronchial

glands and egso pancreas secrete mucus that is not normal which can’t be excreted
so it congests in canals. Dilation occurs (cysts), degeneration of parenchyma,
fibrosis, decreased juice secretion, insufficiency of pancrease.

Insufficiency: decreased juice – uncoplete digestion, malabsorption. Without juice

25-30% of protein can be digested (enzymes from intestines) and fat. Some of the
fat and protein go in stool – steatorrhea, creatinorrhea.

108. Syndrome of malabsorption

For normal absorption food must be digested, absorptive surface must be big
enough, motility must be normal, lymph vessels must be free, perfusion normal
and state of mucosa must be good. If one of these factors is affected then
absorption will occur and organism will suffer the consequences: low nutritional
absorption.

Maldigestion: lack of chemical digestive processes in lumen or wall of mucosa

seen due to decreased enzymes (pancreatitis)

Malabsorption: in situation where intestine part is surgically removed or

anastomosis so abs. surface is not big enough. Also it’s seen in hypermotiliy (no
proper contact). Since lipids are absorved by lymphatics any obstruction in them
will cause malabsorption.

After maldigestion and malabsorption important factors are anatomical and

biochemical changes. In regional enteritis absorption in some parts is almost
impossible. Depends from urea, resections, bacteria, peristalsis.

Raidation enteritis: due to radiation there is atrophy of intestinal epithelia

Genetic lack of lactase: disaccharide stays in lumen and it ferments causing

cramps, bloats, diarrhea.

Diabetes: degenerative change in autonomic ganglia that decreases peristalsis

Malabsorption is classified in selective, partial, total

Dg.: diarrhea, decrease in body weight, pain, weakness. Specific symptoms:

anemia, bleeding, changes in oral cavity and bones. Lab: decreased Ca, K, protein.

109. Etiopatogenesis in tumors for digestion

Etiology: in tumors of digestive tract big role has clinical carcinogenesis for
development which is related to substances in food (by geographical incidence)

Some products have cancerogeneous properties or they can get them during
preparation or conservation: alfatoxins. There is a correlation between food habits
and carcinomas. Gastric carcinoma is caused by smoked food and nitrates.
Colonorectal: increased carbohydrates in food is the cause.

Important are precancerogeneous states. In gizzard: atrophic gastirits, hypertrophy

of mucosa, inflammations and polyposis for colon.

Patophysiology: Vegetative tumors grow in lumen and cause obstructions.

Depending on their location they can cause difficulties in swallowing, food
passage, illeus, etc.

Infiltrative tumors: illeus, stenosis and scaring with metastasis and vomiting.

Ulcerative: bleeding, perforation, peritoneitis. Besides bleeding early symptoms

are painful abdominal disturbances of different localizations depening on tumor
localization. Characteristic is early manifestation of nausea and disgust towards
food so there is loss of weight due to malnutrition and maldigestion.

Diagnostic: Zollinger Ellison syndrome, ulcers are forming on non usual places
and hypergastrinemy is present. It’s confirmed by endoscopy, biopsy and
pathohistologic examination. When symptoms occur usually it’s too late for
treatment. There is an early detection tst based on occult bleeding. If hemoglobin is
present then patient is sent to endoscopy.

110. Etiopatogenesis of allergic and autoimmune disorders of

digestive organs
In mucosa of digestive tube lymphoid tissue is found (peyer plate) and in epithelia
lymphocytes are found. Activated Peyer plate produces lymphocytes that go to
epithelia so they can react. Important constituent of this immunity are M cells also
which by phagocytosis take antigen and present it to antibody in Peyer plate.

This immune system has a role to protect against microorganisms and to form
tolerance for protein molecules from food. This system can change its function and
instead of protection it can develop local hypersensitivity reactions and
autoimmunities that are seen in genetically predisponed persons. There is increase
in diseases of digestive tract that are doubted to occur due to pathologic action of
immune syste: gastritis type a, allergy, gluten enteropathy, chronic intestinal
inflammation, etc.

CG type a: progressive atrophy of glandular epithelia with loss of parietal and chief
cells. Histologically it occurs gradually. First only superficial mucosa is affected,
then atrophy occurs which leads to final atrophic gastritis with thin mucosa. By
distribution there is type A and B. Consequences are achloridia, hypergastremia,
b12 defficiency.

Food allergy: unwanted immunologic reaction mediated by IgE. All states which
cause difficulties in GIT after food intake represent food intolerance. It can be
metabolic (no enzyme – lactase), pharmochemical, GIT (malabsorption),
psychological, etc. Allergy is seen in genetically predisponed persons usually
(nuts, fish, strawberry) so intestinal immune system secretes IgE.

Gluten enteropathy: autoimmune disease of small intestines in genetically

predisponed persons that manifests after cerals consumption. Clinially is
manifested by abdominal pain/cramps, diarrhea, bloating, decrease in body weight,
fatigue, anemia. All of this is caused by gluten, actually part of it (glialine) which
when in contact in epithelia provokes damage. This epithelia gets desquamated so
there is villi flattening. In crypts enterocytes regenerate and there is an
inflammatory reaction. Mechanism: autoimmunity due to tissue transglutinase
which forms complex with glialine (autoantigen). If cereals are excluded from food
menu changes vanish but if the cause is not discovered early then mucosa due to
changes in malapsorbative.
Chronic inflammatory intestinal disease: inflammation in intestines caused by
immune system. When it affects small intestines it affects all walls which leads to
thickening, infiltrations and ulcerations that fo in muscular portions provoking
fistules andpainful tumefactions. This form is seen in 20% of people and it’s called
regional enteritis (Crohn disease). When it affects colon it affects only
mucosa/submucosa and produces ulcerations on whole colon and then it’s called
ulcerative colitis (30%). Other 50% - ileocolic colitis due to inflammation that
affects small and big intestines. Disease occurs due to interaction between genetic,
bacterial, immunologic and environmental factors. These persons have sensitivity
to emotional stress. Nowadays its considered as autoimmunity where organism
attacks GIT. Clinically mucus and blood in stools is seen (ulc. colitis), Crohn –
abdominal pain, anorexia, nausea and increase in body temperature.

111. Etiopathogenesis of liver failure

It can occur in acute form (more than 80% affected) and chronic which develops
gradually. Also it can be primary and secondary (h failure, typhus). By degree of
damage it can be moderate, intermediate and severe. Etiologic factors are divided
in several groups: infective, toxic, chemical, drugs.

ALCOHOL AS ETIOLOGIC FACTOR: ETHANOL in our organism oxydises to

water and carbon dioxide and smaller percent is excreted by kidneys, sweating and
lungs. Oxidative degradation is done by 3 mechanisms:

Alcohol dehydrogenase acts in gizzard and it represents a first pass in metabolism

where 20% is degraded. Biggest portion of this enzyme is in cytosol of
hepatocytes. It’s responsive for biggest degradation of alcohol.

Microsomal ethanolic oxidative system is found in microsomes of hepatocytes.

Catalase does oxidation of methanol. If methanol poisoning occurs ethanol is given

so oxidative system is oxydising more ethanol and methanol oxidation is decreased
so smaller amount of it will transform to formic acid.

Security reference value for ethanol without consequences is 30-40g a day for
females and 40-60g for males. Dnagerous is 160g/day for 5 years.
Ethanol has direct toxic action on hepatocytes and liver damage and it’s seen in 3
forms:

Fatty infiltration is overload of hepatocytes by fat due to alcohol, diabetes, obesity

and toxins. In alcohol consumption this is 1 st reaction. If consumption is persistant
fat amount will increase while protein decreases. If it stops at that time is reversible
in several weeks and it’s usually asymptomatic.

Alcoholic hepatitis can be diagnosed only bi biopsy. Usually it’s seen with
hepatomegaly and with an increase in enzymes. By biopsy centrolobular
degeneration and hepatic necrosis occurs. Also by biopsy besides fatty infiltration
there are hyaline bodies seen (Malary bodies) and increased size of mitochondria.

Alcoholic cirrhosis is the most severe form. In liver there is accumulation of

fibrous tissue. It follows other disorders. Bilirubin is increased aswell prothrombin
time.

MEDICATION: liver damage by medication occurs in two ways. Directly when

necrosis dominates and damage depends on dose and indirectly due to
hypersensitivity reaction (antibiotics, tetracycline, steroids, etc.)

OTHER: Biliar obstruction, autoimmunity (lupus), congenital (glicogenosis where

it accumulates in liver), infiltrative (sarcoidosis, cystic fibrosis, tumor)

112. Pathophysiologic consequences of liver failure

Disorder in bilirubin metabolism, blood flow disorder in liver, neuropsychological
and coma, metabolism of water disorder, hematological disorders (ALL OF
THESE QUESTIONS ARE EXPLAINED IN NEXT PAGES). Protein metabolism
consequences: decrease in albumin, increased globulins, glycemia and lipid
disorders. General: weakness, infections, increase in body temperature.

113. Metabolism of bilirubin disorder in liver failure

During the day 5mg/kg of bilirubin is produced. This metabolism is divided in 3
phases.

Splenic: hemolysis of old red blood cells where hemoglobin gets released. Red
blood cells are degraded by hemooxydase and hemoglobin is left (green). By loss
od Fe atom – biliverdine and then by globin separation under influence of
reducatses – bilirubin (red). Bilirubin by blood goes towards hepatocytes in a
complex with albumin which is a big molecule so there is no any in urine. When
concentrations are 20x bigger then usually then albumin is saturated and it passes
with bilirubine through blood brain barier where it accumulates on basal ganglia
and damages CNS.

Hepatic consists of three processes:

 taking bilirubine anyon from albumin that occurs in sinusoids toward

hepatocytes
 conjugation: detoxication. usually not in big amounts in serum and urine.
When conj. bilirubine increases since it’s water soluble it passes in urine.
Possible disorders: Zilber syndrome, neonatal jaundice which are not so
dangerous but there are some like Creyter Nayar (no enzymes) where
bilirubin is increased 40x. Kids die in 1st year.
 secretion: conjugated bilirubine goes in bile ducts. Possible disorder is
excretion of it, gestational jaundice where only conjugated bilirubine
increases.

Intestinal: bounded (conjugated) bilirubine comes in intestines. In colon by

bacteria is transformed to urobilinogen. By stool it goes out as starcobilinogen and
on air it starts to convert in stercobiline. These are bile pigmentation which color
the stool. From intestines 1 portion of urobilinogen goes back to liver by
enterohepatic circulation and it’s converted to bilirubin. Urobilinogen from liver
that came by enterohepatic circulation (some amount of it) goes in blood then in
urine.

114. Non conjugated hyperbilirubinemia

Increase of concentration over 170 micro mol per liter.
Hemolitic neonatal disease is non conjugated hyperbilirubinemia that is seen in
mismatch of Rh group between mother and kid. Due to hyperhemolysis in neonates
by antibodies from mothers bloodstream concentration of non conjugated
bilirubine increases drastically. If its over 300 micro mol per liter then albumin
will be saturated and non conjugated bilirubine will enter brain where it
accumulates on basal ganglia. This is called kernicterus that leads to mental
retardation.

Infective erythropoiesis is seen in talasemic syndrome, pernicious anemia,

erythropoietic prutpura, Pb intoxication. Life span of red blood cells is normal but
hema implantation is decreased.

Physiological jaundice of newborns: seen after 2 days and it vanishes slowly to 7 th

day. It occurs due to increased degradation (in uterus more is needed, air is
decreased), decreased bilirubin taking, decreased activity of glucorinyl transferase,
and increase in enterohepatic circulation is seen in 50% of newborns.

Gilbert sundrome: autosomal dominant that usually affects males. Jaundice is seen
after stress.

115. Conjugated hyperbilirubinemia

Increase in conjugated bilirubin is seen due to difficult excretion of it by bile ducts.
Since its water soluble when its amount increases in blood it can be seen in urine.
In intestines there is going to be decreased bilirubine which decreases urobilinogen
so stool is hypocholic and decreased urobilinogen in urine.

Intrahepatic cholestasis: seen in hepatitis and biliar cirrhosis. Process affects portal
region and compromits bile capillaries.

Extrahepatic: it’s obstructive jaundice seen due to carcinoma in head of pancrease,

biliar calculosis, scarification of bile ducts. All bile content through sinusoids
enters circulation.

In both forms itching is seen weeks before jaundice.

Dubine Johnson syndrome is rare, difficulties in passage of bilirubine to membrane
of bile ducts. Liver is dark.

Rotor: similar to the syndrome above but there are no pigments in liver (not dark).
Disorder is in bilirubine so there is no cholestasis

Hepatocellular jaundice: these hyperbilirubinemias are most common in clinical

practice. They are seen in many liver diseases, hepatits, cirrhosis. Increase in
bilirubine occurs due to: retention (decrease in number and functionality of
hepatocytes so there is decreased taking of bilirubine and increased conjugated),
obstructions (difficult passage of bile through ducts in portal region due to cellular
infiltration or scarring tissue).

116. Differential diagnosis of jaundice (icterus)

Main problem is to differentiate obstructive from hepatocellular jaundice while
hemolytic is seen in small percentage. By lab is difficult to distinguish since
affected hepatocyte system damages also bile ducts and vice versa.

Differential diagnosis can be done by persistent check ups with 3 diagnostical

procedures. Clinical (anamnesis), lab and diagnostics by ultrasound and MRI.

Main normal regurgitationa retentive hepatocellular

characteristic l
s
blood bound 0 +++ 0 ++
free + + +++ ++
urine bound 0 +++ 0 ++
free + 0 +++ ++
stool bound 0 0 + 0
stercobilinoge ++ 0 +++ +
n

In hemolytic concentration of free bilirubine and urobilinogen icrease

In obstructive bound bilirubine, urobilinogen increases aswell in hepatocelular

in obstructive uro and starco are not present while in hepatocellular yes

These clear differences are seen only in early phases of disease while later they can
change.

117. Disorders of circulation in liver failure

In normal circulation pressure in portal vein is from 8-13mmHg. After entering the
liver portal vein is divided in smaller branches and ends up in portal space. From
there blood with arterial blood flows by small blood vessels then sinusoids towads
v. centralis. Every barrier which increases vascular resistance or stops blood flow
in any part will cause stasis and hypertension distally from it’s localization. By
localization it can be prehepatic, hepatic and post-hepatic.

Prehepatic: thrombosis or compression of v. portae and thrombosis of v. lienalis

Hepatic: liver diseases, mostly in cirrhosis when fibrous tissue compromises blood
vessels

Posthepatic: occurs due to changed vascular resistance above liver (hepatic vein, v.
cava inf.). It’s seen in right heart failure, pancreatitis or in compression of veins by
tumors. Mostly the cause of portal hypertension is seen in liver cirrhosis.

Portal hypertension leads to 3 gropus of disorders:

Collateral circulation: pathway of blood flow from v. portae that passes liver and
goes in venous circulation. It develops in prediction places: between v. coronaria
ventriculi and v. gastrica breves, in front of abdominal wall (varicose veins in front
of belly button), rectum and places where abdominal organs are in contact with
retroperiotenal tissue or they are ingrown with abdominal wall (kidneys)

Spelnomegaly: increased size of spleen due to venous congestion and it’s a form
of secondary hyperslenism. Hematological changes are anemia, leucopenia,
thrombocytopenia, reticulo endothelial system hyperplasia that leads to increased
hemolysis. Splenomegaly occurs in many diseases which indicate its increase in
function. It occurs by several basic mechanisms: inflammation, congestive due to
decreased blood flow (cirrhosis), infiltrative, hyperplastic, extramedular
hematopoiesis, tumors. Splenomegaly can be asymptomatic or symptomatic. If it’s
symptomatic then pain is felt under left side of rib arch and there is bloating of the
stomach. Most expressed splenomegaly is seen in chronic granulocyte leukemia.
Hyposplesnims is decrease in its size due to decrease in function and it’s seen in
sickle cell anemia and infarcts.

Ascites: free fluid in abdominal cavity that comes in 75% of cases from liver
cirrhosis. It occurs by local and general mechanisms. Local: increased pressure,
lymph amount, permeability and reasbsorption. General: oncotic pressure decrease
(hypoalbuminemy), retention of sodium and water. These lead to edema that is
seen on legs, hydrocele, hydrothorax. Ascites leads also to alveolar
hypoventilation, increased abdominal pressure. It can be removed by abdominal
puncture.

118. Neuropsychological –hepatic coma

In liver damage by external circulation which overcomes liver (detox) material go
straight in systemic circulation. They come to CNS provoking systemic portal
encephalopathy and most severe form of this disorder is hepatic coma.

SPE is usually seen in cirrhosis but it’s not specific for it since it can occur in other
acute liver disorders without cirrhosis (viral hepatitis). With right treatment it can
be reversible. Besides collateral circulation and decrease in detoxication important
for pathogenesis is increase in intestinal bacterial flora due to stasis. From all toxic
material ammonia is most known which is normally produced in colon but it’s
detoxicated in liver. In liver ins. and portal hypertension infective agents go to
small intestines (stasis – multiplication) so there is an excess in ammonia. In
hepatic coma concentration of ammonia in plasma increases. Special form of
hyper ammonia in acute hepatopathy is called Rey syndrome and it’s seen in kids.
Encephalopathy, disorder in liver and increased ammonia together are resulting in
30% lethality of kids. Concentration of fatty acids increases, amino acid
metabolism is disturbed, increased serotonin.

SPE is manifested as psycho-intellectual disorder that is developing in 4 stages

Psychic symptoms: euphoria, depression, confusion, decreased thinking, speech is
gapped, patients sleep during day, etc.

Neurological: tremor, non coordinated movements, hyperreflexia/hyporeflexia

Acute SPE: intoxication and viral hepatitis are the cause

Chronic: usually due to cirrhosis

Endogeneous coma: terminal insufficiency of hepatocytes

Egsogeneous: occurs due to increase in ammonia, lots of meat intake, alcohol,

medication, constipation

SPE: sometimes is reversible

119. Disorders in water, electrolytes and minerals in LI

In advanced cirrhosis ascites occurs that leads to hypovolemia-hypoperfusion-
aldosteron-retention of water and sodium-decrease in potassium.

Special disorder in cirrhosis and ascites formation is hepatorenal syndrome. It’s a

insufficiency of liver/kidney where besides LI and portal hypertension suddenly
kidney insufficiency forms with oligura, electrolyte disbalance and increase in
nitrogen compounds. In hepatorenal syndrome development major role has
intrarenal vasoconstriction due to hypovolemia. Glom. filtration decreases,
ologuria and hypernatremia occur. Hypovolemia is caused by diuretics, abdominal
puncture in ascites removal, vomiting, bleeding, etc.

Endocrine disorders: lots of them occur due to non adequate metabolism of

hormones. Estrogen, cortiosl and ADH are increasing. Aldosternoe is disturbed
with all symptoms present.

Estrogen: spider angioma and other skin changes. In males: pubic hair loss, erectile
dysfunction, gynecomastia, infertility.

Cortisol: acne, stretchmarks (Cushing)

 120. Hematological and hemostasis disorders in LI
In this group of consequences are pancytopenia and disorder of hemostasis

Anemia: due to increased hemolysis and hemostatic causes that lead to bleeding. In
cirrhosis small bleeding from gingival, genitals and nose are frequent. Decrease in
production of red blood cells occurs due to low levels of protein, Fe and vit. B12
which is most expressed in alcoholics. Since liver is damaged there is a decrease in
production of coagulative factors, platelets decrease, fibrinolysis occurs, etc..

121. Biological biochemical disorders in diseases of liver

Most accurate diagnosis is achieved by biopsy and pathological histological
checks. In clinical practice besides pathophysiological parameters ultrasound, CT
and MRI are useful. In liver diseases we examine:

Biological biochemical syndrome of inflammation: increased alpha and gamma

globulins, increased erythrocyte sedimentation rate, leucopenia, monocytosis, etc.

Syndrome of hepatocyte insufficiency is show as increase of inflammation factors

(listed above), decrease in albumin and coagulative factors. Ammonia increase in
SPE

Syndrome of biliar retention: increased bile content in blood, conjugated bilirubin

increases and in urine there is an increase in amount of urobilinogen

Syndrome of hepatocyte necrosis (toxic/non toxic). Due to inflammation and

increased permeability enzymes concentration in blood increases.
Aminotranspherase, glutamate dehydrogenase, lactate dehydrogenase, malate
dehydrogenase..

122. Etiopathogenesis and consequences of cholelithiasis

In biliar tract cholelithiasis is the most common disorder. That is the presence of a
calculus of different size, shape, content, consistency, etc. It can be asymptomatic
or followed by some symptoms.
By content calculus can be cholesteric, pigmented (bilirubin) or mixed

By number from 1 calculus to several hundreds

If calculi are in bile sack in up to 25% they are formed in ducts also. If they are
present in smaller number they are usually round while if present in bigger amount
then they are irregular in shape (friction)

Etiopathogeneisis: there is differentiation between cholesteric and bilirubin

cholelithiasis. Cholesteric are formed due to disorder in relation between
cholesterol, bile acids and lecitine. Bile that has predisposition for calculi
formation is called lytogenic bile and its characteristic is that it contains bgger
amount of cholesterol. Bilirubin calculi show up in hemolytic diseases due to
increased amount of bilirubin that comes through bile. Mixed occurs due to both
characteristics from above + presence of calcim which is seen in pregnancy,
infections of bile sack, etc. They are slowly developing.

Consequences: pain under right rib arch after fatty food intake or food that is
difficult for digestion like beans. Pain is usually followed by vomiting and it’s seen
2-3h after meal. This pain is called biliar colic. Pain results from increased pressure
in bile ducts due to calculi movement towards cystic duct which gets obstructed.
Mechanical damage also results in pain. Many consequences occur: acute
cholelithiasis that can pass to chronc form, perforation of bile sack, obstructive
jaundice with increase in bilirubin, accumulation of calcium in walls that makes
contraction more difficult, carcinomas, pancreatitis, etc. Clinical treatment
considers surgery with removal of calculi.

123. Changes of urine amount in urinary syndrome

Different kidney and other disorders can provoke changes in amount and content
of urine. Changes in amount are: oliguria, anuria, polyuria. Oliguria is less than
500ml for 24 hours, anuria less than 100ml and polyuria when urine exceeds
2000ml per day.

Oliguria can be prerenal, renal and postrenal depending on cause.

Prerenal is seen in all states that provoke hypovolemia and low blood pressure or
states where reabsorption is increased. These disorders occur as a consequence of
liquid loss (diarrhea, vomiting, sweating) or blood loss. Basic mechanism in
oliguria development in this cases is decreased filtrational pressure in glomeruli so
there is a decrease in glumerular ultrafiltrate with normal reabsorption and water
retention. Water retention is under aldosterone and ADH influence as a
compensatory mechanism due to increased minute bloo volume. Small amount of
highly concentrated urine is excreted.

Renal is caused by disorder in kidney function due to many mechanisms. All

kidney diseases decrease strength of GF due to decrease in FP or active surface. If
strength of GF is decreased in all nephrons then glomerulo-tubular balance is
disordered in favor of tubules for water reabsorption which decreases urine
amount. This is seen in acute glomerulonephritis where GF is decreased due to
inflammation which increases resistance to blood flow in glomeruli and results as a
decreased FP with saved tubular function. If some of the nephrons are not affected
then the healthy ones will undergo hypertrophy with increased GF in them but total
GF is still decreased. In chronic glomerulonpehritis degenerative changes occur
which decreases filtrational surface. In chronic kidney insufficiency amount of
nephrons is decreased hence functional surface, GF decreases and tubules
decrease.

Postrenal: usually due to kidney calculi or tumor that obstructs urinary canals.

Anuria: no urine coming to bladed.

Retention of urine: urine is present in bladder but urethra is obostructed.

Polyuria

Prerenal: all states which give increased perfusion of kidney (hypervolemia) or

decreased reabsorption of water in tubules. Basic mechanism is increased FP with
low reabsorption. Increased liquid intake, decrease of osmotic pressure of plasma
and decreased ADH can cause increased amount of hypoosmolar urine. It’s seen in
diabetes inspidus (hypophysis problem), psychological polydipsia, renal diabetes
inspidus (no proper answer to ADH).
Renal: in many chronic kidney diseases with glom-tub disbalance in favor of
glomeruli with decreased water reabsorption in tubules. This is usually seen in
tubulointerstital diseases, early stages of CKI. Polyuria is followed by nocturnal
urination. Polycisuria: frequent urination (inflammation) but there is no increase in
amount

Postrenal: after deobstruction – urine caused damage to parenchyma (tubules)

124. Changes in urine content

This analysis is the most important non invasive method in kidney evaluation.
Important are: proteinuria, cilindruria, hematuria, leucocyturia and bacteriuria.

Proteinuria is normal around 150mg a day. 10-15mg of albumin and 135mg are
plasma proteins. In normal circumstances one portion of albumin with other
proteins of small mass pass through GCM (glomerulo-capillary membrane). In
proximal tubules they are reabsorbed and then degraded by proteolyitic enzymes.
By mechanisms proteinuria can be prerenal, postrenal and renal.

Renal: in many kidney diseases where glom/tub function are affected. Depending
if they are caused by increase in permeability of GCM or tubule damage they are
classified as: glomerular, tubular and mixed. Glomerular represent increase of
permeability of GCM in glomerulonephritis where there is damage and change of
structural and electrostatic components in glomerular capillaries. Besides these
changes enzymes are released which increase transmembraneous passage of
proteins. If GCM is slightly damaged then proteinuria is selective (albumin and
smaller). If damage is severe then it’s non selective. Tubular is seen when tubules
are damaged which is seen as a consequence of disorder in tubular reabsorption
and catabolism of proteins of small mass. It’s seen in tubulointerstitial
nephropathy, analgesic nephropathy, etc. In difficult chronic kidney diseases where
besides GCM disorder also tubular disorder is present in urine proteins of bigger
molecular mass will be seen. These proteinuria are glomerulo tubular or mixed.

Prerenal: called also overflow proteinuria when permeability of GCM is normal

but it occurs as a consequence of increased amount of plasma proteins of small
molecular mass. It’s seen in plasmotoma and other paraproteinemias characterized
by increase in immunoglobulins which overpass reabsorptive capacity of tubules
and they are seen in urine as Ben Johnson proteins. Also this occurs in increased
intravascular hemolysis when increased amount of hemoglobin overpasses
capacity of haptoglobine so it gets excreted in urine.

Postrenal: it’s not a real proteinuria since IgA and IgG from exudates mix with
final urine.

PROTEINURIA IS NOT ALWAYS A SIGN OF DISEASE, IT CAN BE SEEN

AFTER HIGH PROTEIN MEAL, IN FEBRILE STATES OR STATES OF
INCREASED PHYSICAL EFFORT.

Cylindruria: protein sediment that originates always from kidneys. In urine of

healthy person we can always see some hyaline cylinders while other (red blood
cell cylinders, wax c., fat c.) are pathologic. Wax cylinders are yellow and they
indicate severe damage of tubules. Red blood cell cylinders indicate glomerular
damage. White blood cell cylinders are seen in interstitial nephritis and fat
cylinders are seen in nephritic syndrome.

Hematuria: in sediment of urine usually 1-3 red blood cells are seen. It can be
microscopic and macroscopic. By mechanism it can be prerenal, renal and
postrenal. Renal is seen when red blood cells are present due to damaged GCM in
glomerulonephritis, vasculitis or tubulointerstital damage.

Prerenal: cause is disorder in hemostasis like hemophilia or it’s seen during

anticoagulant therapy

Postrenal: fresh red blood cells that come from ureter, urethra, prostate, tumor or
inflammation.

Lecucyturia: normally in urine are present 7-8 white blood cells. Piuria represents
degenarted white blood cells from intersitium. Lecocyturi and piruia with
hematuria is seen in infections. In bacterial infection – n. granulocytes. In allergy –
e. granulocytes. In viral infections – lymphocytes

Epithelia: it’s seen from tubules, ureter, bladder, vagina, etc. Only tubular
epithelia has diagnostic value since it indicates damage from glomerulonephritis or
nephritic syndrome.
 125. Etiology and pathogenesis of acute kidney insufficiency
It’s characterized by syndrome with expressed fall in glomerular filtration,
retention of material and changes in values of extracellular fluid, electrolytes and
acid base balance. By cause AKI can be divided in prerenal, renal and postrenal

Prerenal or circulative is most common form of AKI and it represents a

physiologic response to hypoperfusion of kidney. Parenchyma is not damaged so
function of kidney goes back to normal as soon as the cause of decreased blood
flow is removed. If hypovolemia is prolonged ischemic damage occurs so
parenchymal AKI develops. Hypoperfusion can occur due to bleeding, burns,
vomiting, diarrhea, decreased minute volume, increased vascular resistancy, etc.

Renal AKI or parenchimal is seen when parenchyma is damaged due to tubular

necrosis by ischemia or toxins. The cause in ischemic form is hypoperfusion and it
has 3 phases of development. Initiation: several hours to days from damage. Force
of glomerular filtration decreases and filtration pressure decreases. Due to necrosis
ultrafiltrate is drained in interstitum and comes back to blood stream. Maintaining
phase: urine amount decreases, glomerular flitration is 5-10ml/minute and nitrogen
compounds increase. Loss of kidney function provokes disbalance in water and
electrolytes, hyponatremia, intoxication with water, heart failure, hypercaliemia,
hypocalcemia, hyperphosphatemia. Toxins can’t be excreted which results in
iremia with GIT bleeding that leads to anemia, cns damage and infections.
Recovery phase: lasts up to 3 weeks, functions recover and it has 2 phases. In first
GF recovery occurs with increase in strength and in late phase tubules recover.

In nephritic form (toxins) necrosis is less expressed than in ischemic form. It can
be followed by normal diuresis. It occurs due to mechanisms of vasoconstriction
(intrarenal) or by many antibiotics that induce this form of AKI (cytostatics). Most
common nephrotoxins are Ca, hemoglobin and oxalates. Hemoglobin directly
damages tubular epithelia. Calcium is compromises strength of GF with intrarenal
vasoconstriction and deposition of calcium phosphate.
Postrenal or obstructive: it’s rarest form seen due to difficulties in elimination of
urine caused by obs. urethers: calculus, blood clot, tumors. If only one kidney is
affected then the damage is not so serious due to compensational reaction from 2 nd
kidney. Above obstruction place there is increased pressure with decrease in
filtrational pressure and filtration. If obstruction lasts longer parenchyma gets
damaged which can lead to postrenal and renal AKI. Most common obstruction is
obstruction of urinary bladder neck.

126. Pathophysiological changes in AKI

Decreased excretory function increases metabolic products in blood so there is
increase in urea, creatinine, ureic acid and others that contain nitrogen. Retention
of different protein and amino acid products can have toxic effects. Disorder in
hemostasis of water and electrolytes and acid base balance is manifested as
decreased excretion of water with hyponatremia, hypercaliemia,
hyperphosphatemia, hypocalcemia and acidosis. Oliguria or anuria is seen in up to
80% of cases with edema. Decreased function of kidney disorders other organs
where CV system, GIT, CNS, hematopoietic, endocrine and immune system
dominate. In CV system due to overload with excessive fluid hypertension will
form. Nervous system gets damaged from toxins or acidsis. GIT bleeding occurs
due to increased gastrin amount. Hematologic changes include anemia,
thrombocytopenia (bleeding).

Since in kidney erythropoietin, dihydrocalciferole and rennin are produced and

insulin, glucagon, gastrin, prolactine, ADH, angiotensin are metabolized there are
many disorders.

In immune system due to lyphopenia and lecopenia recurrent infections are seen.

Mortality by AKI is high despite the fact that it can be reversible.

In laboratory: decreased amount of urine. Sediment: in prerenal – normal, postrenal

– normal with hematuria sometimes. If sediment has brown cylinders, tubular
epithele then it’s renal AKI + hematuria and proteinuria
 127. Etiology and pathogenesis of CKI
CKI is clinical syndrome characterized by progressive and irreversible loss of
functional nephrons to terminal stadium where dialysis or transplantation of kidney
is needed.

CKI can be caused by many chronic diseases like diabetic nephropathy,

hypertensive nephropathy, glomerulonephritis and others. Depending on
underlying disease mechanism of development is different but in common they
have progressive loss of nephron functionality. This decrease in function provokes
hypertrophy of healthy nephrons. This provokes sclerosis of functional nephrons
with further progression of CKI which results in irreversible changes. By Bricker
theory when functional loss is bigger all functions are done in healthy nephrons.
This increases GF and secretion of some substances so excretion of water and
substance per nephron is bigger. At the same time retention decreases. Changes
occur due to activation of specific mechanisms that depend on strength of GF.
Creatinine and urea are excreted until SGF=50%. Plasmatic concentration of
substances whose excretion depends on tubular reabsorption and secretion
(p,ca,k,nh4) gets increased when SGF=25%. Kidney in states of severe reduction
of nephrons maintains efficiently balance of water and sodium so their retention
occurs when SGF=5%.

CKI develops in 4 phases.

Kidney hypofunction: decrease in number of functional nephrons. SGF is dropping

down and compensating mechanisms are activated in manner that healthy nephrons
by their increased work stop accumulation of nitrogen and water in extracellular
fluid so they compensate decreased functionality of other nephrons. In healthy
nephrons increased glomerular filtration and blood flow/pressure = adaptive
hyperfiltration-hypertrophy-normal function.

Compensative retention: when nephrons are less then 50% functional there is
reduction of SGF so nitrogen substances are retentioned (urea, ureic acid and
creatinine). Filtration and osmotic load per nephrone is increased which results in
decreased tubular reabsorption of water and sodium and decrease in concetrational
ability of kidney with increased amount of hyperosmolar urine. By this
homeostasis of electrolytes is obtained. Fat and carbohydrate metabolism is
disordered in advance of this phase and due to enzymatic inhibition
hypertrigliceridemy and glucose intolerance is seen.

Decompensated retention: function of nephrons is decreased for 75-90%. SGF is

decreased which leads to even bigger increase in nitrogen materials. By drop in in
functionality hypercaliemia and acidosis is seen.

Uremia: function is completely lost. There is loss of excretory, regulatory and

endocrine function with multiorganic failure. Increase in nitrogen material in and
other metabolic toxins is seen. Value of fluid is disbalanced. Hypotonic
hyperhydration is seen or hypertonic dehydration.

128. Pathophysiological consequences of CKI

It affects all organs and systems.

Metabolism: protein metabolism disorder occurs due to decreased excretion of

degradational protein products and from enzymatic disorder which leads to acid
base disbalance. Due to hyperinsulinemia (decreased metabolizing in tubules)
synthesis of triglycerides is increased and this leads to atherosclerosis

Hematologic: anemia is seen due to decrease in erythropoietin and toxic effects of

uremic toxins, decreased Fe (GIT bleeding) and folic acid decrease. Since platelets
are disordered bleeding is seen and infections due to secondary immunodeficiency.

Body fluid: water and electrolyte balance depends on underlying cause that caused
CKI and fluid intake. There is tendency to retention or loss of water and sodium
with certain consequences. In CKI when water intake is not overcoming kidney
capacity – hypertension – edema/heart failure. There is damage of kidney
mechanism for water and sodium sparing. In normal circumstances sodium is not
reabsorbed (only 1%) while it occurs in terminal phase – hypervolemia –
hypertension – edema (cns, lungs). In patients with CKI potassium is excreted
more via GIT so hypercaliemia is seen. Hypocaliema is seen when excretion via
GIT increases or when food intake is decreased.

Acid base disbalance: it occurs in third phase of CKI development and it’s seen as
metabolic acidosis. Kidney, intracellular buffer systems and breathing stop its
development and it’s not seen before SGF=20%. There is low excretion of
hydrogen ions with decreased regeneration of bicarbonates in tubules due to
decreased ammonia. Phosphate, sulfate and anions of organic acids increase with
decrease of SGF and all of this leads to acidosis. To metabolise hydrogen bone is
releasing its minerals. Hyperphosphatemis is seen due to low excretion. Hormone
D synthesis decreases which decreases Ca absorption = PTH increases.

129. Patophysiology of uremic syndrome

Symptoms in advanced kidney disease.

Disorders that occur are consequence of reg/met/endo function effects from

anemia, hypertension, protein metabolism, carbohydrate metabolism, fat
metabolism, bones, etc.

Disorders are classified as: due to retention, due to excretion.

Degradational products of protein metabolism are primary excreted by kidney so in

case of decrease in GF their retention will occur.

Uremic toxins act on cellular level provoking Na-K pumps, ATPase, and other
enzyme disorders.

Urea can lead to anorexia, nausea and headache

Guanodisucyl acid leads to platelets damage

Polyamines inhibit erythropoiesis which leads to anemia

Hormones increase not only due to decreased catabolism but also due to increased
synthesis since tissue is more resistant for hormones (toxin damage) which can
lead to endocrine disorders

GIT: anorexia, nausea, vomiting. Ammonia from urea is seen in mouth so smell of
breath is urine like. Dried mucosa with ammonia inflames oral cavity and peptic
ulcerations are seen throughout GIT
Cardiopulmonal: arterial hypertension is most common complication due to
glomerulo tubular disblanace, activity of RAA and decreased vasodilatory
prostaglandins in parenchyma. In uremia basic cause is overload with fluid which
overloads heart and leads to congestive heart failure with edema.

Nervous: CNS damage due to osmotic and acid base disbalace. Loss of
concentration, insomnia and then it progresses in changes of behavior and thinking
with muscle cramps. In terminal stage of CKI coma is possible.

Other: decreased testosterone, decreased estrogen, dermatosis, dehydration, Ca

deposits (itching)

130. Glomerular diseases

Characterised by damage of glomerular structures in nephrons. They are classified
as in primary or secondary. Damage of glomeruli=glimerulopathy/nephritis.

Etiopathogeneisis: They are sensitive to inflammatory, metabolic, hemodynamic

and chemical insults. All glomerular damages will result in decreased glom.
filtration and/or protein and blood cells in urine. Glomerular diseases usually show
up from immune diseases, diabaetes or hypertension.

Glomerulonephritis caused by immune mechanisms: by mechanism we differ

immune-complex and cytotoxic GN. In both causes damage occurs due to disorder
in humoral immunity and activation of their effect mechanisms.
Immunocomplexes are formed as a response to endo/egso antigen and they can
accumulate. Most common egso antigens are foreign proteins or infective antigens
while endogeneous are parts of DNA, tumor antigens and autologous
immunoglobulins.

Damage can be in range of all glomeruli (diffuse type) and some glomeruli (focal),
some part of glomeruli (segmented) with proliferation of cells or without.

Glomerulonephirits caused by non immune mechanisms: Usually it’s seen in

diabetic nephtopathy which is characterized by proteinuria and progressive KI.
Intraglomerular pressure increases which causes glomerular damage or arterial
hypertension. Despite the fact that kidney has efficient mechanism for its
regulation if increase is persistent it leads to vasoconstriction and sclerosis of
arterioles – atrophy/scleritc glomeruli. Glomerular damage can be caused by
toxins, abnormal product accumulation, genetic diseases, infection, etc.

Clinical manifestation: Acute nephritic syndrome is sudden, hematuria, proteinuria,

oliguria, edema, hypertension, etc.

Chronic: slowly progressing, hematuria, proteinuria, hypertension

Nephritic syndrome: severe proteinuria, hypoproteinemia, hyperlipidemia, edema,

increased coagulation

Fast progressing nephritic syndrome: sudden hematuria, proteinuria, anemia and

progress of insufficiency.

Urine syndrome: changes depend on progress of proteinuria, hematuria and

cylinders seen

Changes in SGF: in early phases due to decreased nephrons SGF per nephron
increases but total is decreased – kidney insufficiency. In early stage of GN
decreased SGF due to decreased filtrational surface. Later GF is decreased and
blood flow in glomeruli with FP

Blood pressure: increase is seen when large amount of nephrons are lost. In CKI
hypertension occurs due to increased blood amount with vasoconstrictive effects of
angiotensin and decreased vasodilators (prostaglandin, bradykinine). In ANS
hypertension due to decreased SGF and fluid retention

Edema: occur often and are classified as nephritic or nephrotic

Nephritic: in acute nephritic syndrome and progressed chronic. Basic mechanism is

increased hydrostatic pressure by hypervolemia while in chronic not so much due
to good adaptation. In CKI edema due to decrease in GF and tubular reabsorption
so retention of water and sodium occurs.

Nephrotic: decreased coloido osmolar pressure in proteinuria or increased

permeability of glomerulo capillary membrane for proteins is the cause.
 131. Nephrotic syndrome
Occurs as a consequence of increased permeability of GCM for proteins –
increased proteinuria (more than 3.5g/24h), hypoalbuminemy, edema,
hyperlipidemia, increased coagulation.

This is seen in glomerulonephritis, diabetic nephropathy and amyloidosis.

Low concentration of albumin in plasma decreases coloidoosmolar pressure so

fluid from blood vessels is accumulated in interstitial space – edema

Hyperlipidemia – increased cholesterol, triglycerides, phospoholipids. Fat

cylinders are seen in urine (absorbed by tubules)

Hypercoagulability: decreased antithrobine and increased fibrinogen – venous and

arterial thrombosis, loss of hormones, immunoglobulins and transferin.

132. Tubulointerstital kidney diseases

TIKD is a group of disorders where first tubular segment and certain amount of
interstitium is damaged. Most common causes are toxins, infections, ischemia and
immune factors. They can occur also in secondary form with GN, vascular diseases
of kidney or obstructions.

Tubular disorders dominta which results as decreased concetrational ability of

kidney and acidation of urine. This causes polyuria with slight proteinuria.

Most expressed tubular damage is seen in acute tubular necrosis by ischemia or

toxins which lead to AKI. TIKD in great manner is caused by drugs that are
excreted via urine. Adverse effects are increase by increase blood flow in kidney
and concentration of toxins in kidney where low pH affects ionization and
solubility of these substances.

Pyelonephritis: TIKD caused by infection which is manifested as chronic or acute

pyelonephritis. Usually its caused by Gram- bacteria, streptococcus and
staphylococcus. In urine due to inflammation of kidney leukocyte cylinders and
bacteria are seen. In chronic there is scarification of kidney with damage of
concetrational function, retention of sodium, excretion of hydrogen ions with
polyuria.

Metabolic causes: usually they are expressed as nephropathy, hypercalcemic,

hypocalcemic or myelomic kidney.

Urate nephropathy: concentration of urine acid increases which is accumulated in

medulla.

Hypercalcemic nephropathy: increased urine acid and calcium that accumulates in

tubular structures and provokes damage. Also it causes calculosis of kidney.

In multiple myeloma: Ben Jonson protein is seen in urine which binds in acidic
environment with Tom Horsfall bodies – big cylinders, congestion of urinary
canals.

133. Selective disorders in tubular function (tubulopathy)

Tubulopathy represents a group of disorders where 1 or more tubular function is
affected while glomerular function is normal.

In renal glycosuria: reabsorption for glucose in tubules is decreased so glucose is

seen in urine even when concentrations are normal

In renal tubular acidosis acid base disbalance is present with damage of proximal
or distal tubule function. In proximal RTA basic mechanism is disorder in
reabsorption of bicarbonates. In distal reabsorption of bicarbonates is normal but
acidification of urine is damaged so pH is always bigger than 5.5. In
hypercaliemcic RTA acidification is disturbed due to decreased aldosterone or its
effect. Increased pH provokes sedimentation of Ca which leads to calculus
formation.

In nephrogeneous diabetes inspidus: insensibility of tubules to ADH

Pseudoaldosteronism: loss of sodium due to decreased sensitivity for aldosteron

Barett syndrome: decreased reabsorption of salt, increased excretion of liquid
which leads to decrease of extracellular fluid and activation of RAA

Renal hypophosphatemia: leads to demineralization of bones

Hartnup syndrome: disorder in amino acid reabsorption which results in skin

changes, diarrhea and neurologic symptoms.

134. Renal hypertension

Kidneys have a major role in regulation of blood pressure so many diseases of

kidney can affect blood pressure – renal hypertension. By cause in increased blood
pressure it can be renovascular and parenchymal.

Renovascular: due to decreased diameter of renal artery or some of its bigger

branches. Stenosis usually occurs due to fibrovascular dysplasia of its wall or
atherosclerosis. Hypertension will manifest itself only if stenosis, hypoxia and
decreased blood flow are present. This leads to RAA system activation. Treatment
is surgery.

Renal parenchymal hypertension: due to disorders in kidney parenchyma.

Mechanism of development depends on underlying cause.

In chronic diseases of parenchyma (GN,pyelon.,polycystic kidney) hypertension is

seen in 80% of patients. Mechanism: disorder in glomerulo tubular balance, RAA
disorder, synthesis of vasodilators disorder (in parenchyma). Hypertension in CKD
is characterized by disorder in autoregulation of periphery circulation caused by
hypervolemia (kidney cant excrete water and sodium). It can be regulated by
dialysis and water intake.

135. Nephrolthiasis

Disease characterized by calculi in kidney (pelvis or calyces). Kidney calculi are

usually made of Ca salts (75%) and ureic acid. Most common cause is
hypercalcuria, hypoP, hypooxaluria, hyperuricouria. Struvite calculi are produced
mostly by urinary infections with urease+ bacteria. Calculi can be seen in range of
primary or secondary hyperuricemia (ureic acid)

In nephrolithiasis important role have local factors like stasis of urine, anatomical
anomalies in urine pathways, inervation or infections.

First step in calculi rise is formation of core which is the base for new calculus.
Most important rule for crystallization of particles is that its concentration more
increased than its solubility. Process depends on pH, inhibitors (citrate, Mg) and
stimulators of crystallization (obstruction, core). Alkaline urine = struvite and CaP
stones while acidic forms ureic acid stone. When kidney stone core is produced it
starts to grow by aggregation of same kind crystals and growth doesn’t stop when
saturation is normal. Clinical manifestations are: macroscopic hematuria, severe
pain, infections of kidney due to staisis. During spontaneous elimination there is a
possibility for obstruction to happen which when persistent can lead to obstructive
nephropathy.

136. Postrenal disorder in kidney function

Usually occurs due to obstruction of urinary pathways which are mostly hereditary
(aberrant blood vessels that press urether) but also occur due to infections, tumors,
compressions, etc.

These obstructions are usually partial and can be slight, difficult, severe while
complete obstruction is a rarity but if it occurs it destroys kidney parenchyma very
fast. Difficult elimination of urine is obstructive uropathy. If obstructive uropathy
affects also kidney then this is called obstructive nephropathy.

Obstructive nephropathy: obstruction of urether and urine congestion raise

hydrostatic pressure which leads to hypertrophy and dilation of ureter, pelvis and
calyces by liquid. This pressure is transmitted to proximal tubules and Bowmann
capsule which results in decrease of FP and SGF. If in 7 days obstruction is
removed then it is reversible. If obstruction is persistant then infections and
nephrolithiasis is een. If one kidney is damaged other will compensate. If not
chronic renal failure will manifest.