Ministry of Public Health of Ukraine Sumy State University Department of Physiology and Pathophysiology icon

Ministry of Public Health of Ukraine Sumy State University Department of Physiology and Pathophysiology




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Ministry of Public Health of Ukraine

Sumy State University

Department of Physiology and Pathophysiology


Author: Ataman A.V., D.M., Professor and Chair Department of Physiology and Pathophysiology;

Editor: Naumko R.F., Candidate of medical sciences, assistant.


Shot course of pathophysiology – Part 3:


Disturbances of metabolism.


Workbook for medical students and practitioners


Notice: This workbook is presented by review questions and answers and explanations according to program Ministry of Public Health of Ukraine for medical students. May be used by students for preparing to practical classes of pathophysiology in combination with classic textbooks of pathological physiology. Also this workbook can be useful for practitioners (internists, family physicians and other specialists) when it is necessary to review large amounts of material for Medical Licensing Examination.


Sumy 2010


17. Disturbances of the energy metabolism


17.1. What are precellular and endocellular disorders of the energy metabolism?

The disorders of the energetic metabolism connected with disorders of providing of cells by nutrients and oxygen are named precellular. These are starvation and hypoxia.

Endocellular are disorders connected only with the transgressions of the utilization of the nutrients and oxygen by the cells but not with the disorders of providing cells with them.


^ 17.2. Name the reasons of disturbance of providing cells with nutrients.

1. Full (absolute) absence of food or deficiency of nutrients in it.

2. Disturbance (disorder) of the digestion and absorption.

3. Disturbance of mobilization of nutrients from depot (for example, defeats of a liver, disorder of nervous-humoral regulation of a fatty metabolism).

4. Disturbance of transport of nutrients by blood (the general and local disorders of blood circulation).

5. Disturbance of diffusion of nutrients in tissues.

6. Loss of nutrients or their use not to destination (proteinuria, glucosuria, burn illness, malignant tumours).


^ 17.3. What disturbances of a chemical compound of blood testify to disturbances of supply of cells by nutrients?

1. Hypoglycemia - it is reduction of glucose concentration in blood.

2. Hypolipacidemia and hypolipoproteinemia - it is reduction of containing of free fat acids and lipoproteins in blood.

3. Hypoproteinemia and hypoaminacidemia - reduction of the maintenance of proteins and free amino acids in blood.


^ 17.4. Name the reasons of endocellular disturbances of the energy metabolism.

1. Disturbance of transport of nutrients through a cellular membrane (for example, glucose transport at diabetis mellitus).

2. Disturbances of central endocellular catabolic ways in the cell.

3. The derangement of processes of biological oxidation in mitochondrias.

4. Dissociation of processes of oxidation and phosphorylation.

5. Disturbance of transport АTP from mitochondrias to the places of use.

6. Disturbance of use of АTP energy.


^ 17.5. What disturbances of central endocellular catabolic ways can lead to transgressions of energy supply of cells?

1. Oppression of glycolysis.

2. Disturbances of Crebs’ cycle.

3. The derangement of (PPW) cycle.

4. Oppression of oxidation of fat acids.

5. Disturbances of processes of desamination and oxidations of amino acids.


^ 17.6. Name principal causes of disturbances of central catabolic ways in cells.

I. Reduction of the containing of vitamins and (vitamin-like) substances in cells (vitamin insufficiency).

II. Acquired reduction of activity of enzymes:

  1. reduction of activity of separate molecules of enzymes (action of metabolic poisons);

  2. reduction of quantity of molecules of enzymes (transgressions of enzymes synthetic functions of the liver).

III. Hereditarily caused ensymopaties. Numerous genetic defects of enzymes of glycolysis, pentoses cycle, catabolic transformations of amino acids are described. Today any enzymopaties, mentioning Crebs’cycle and β-oxydation of fatty acids are not known.

IV. Deficiency of АТP. АТP is used by a cell for activation of substrates which used in central catabolic ways (for example, phosphorylation of glucose and fructose-6-phosphate, activation of fatty acids). Deficiency АТP creates the "vicious circle" - it destroys catabolic transformations of nutrients that conducts to disturbance synthesis of АТP. It, in turn, increases deficiency of macroergic compounds.


^ 17.7. What reasons can cause development of vitamin insufficiency in cells?

Development of vitamin insufficiency in cells is caused by:

a) hypo- and avitaminosises;

b) Disturbance of transport of vitamins into a cell;

c) Disturbances of transformation of vitamins to the coenzymes;

d) Disturbances of formation of choloenzymes - complexes of co-ensymes with apoenzymes.


^ 17.8. Name the principal causes of disturbance of biological oxidation in cells’ mitochondrias.

1. Deficiency of coenzymes: (NAD, ФМN ubichinone).

2. Deficiency of microelements: Fе (conteins in iron-sulfuric centers of NАDH-dehydrogenase complex and cytochromes) and Сu (it is a part of cytochromoxydase).

3. Blockade of transport of electrons on a respiratory cycle (action of poisons - rotenon, antimicine A, amital, cyanides, oxide carbon (II), hydrogen sulphide; fig. 58).

4. Disturbance of acceptor control of breath (АDP does not control speed of transport of electrons on a respiratory circuit ).


^ 17.9. What is the dissociation of oxidation and phosphorylation? What is its mechanisms?

Dissociation of oxidation and phosphorylation is a condition at which the energy released during transport of electrons on a respiratory circuit, is not capable to be accumulated in macroergic phosphate bonds of АТP and consequently is allocated in the form of heat.

Reduction of synthesis of АТP and increase in consumption of oxygen in cells are characterized for this condition.

In a basis of dissociation of oxidation and phosphorylation following mechanisms can lay:

a) Reduction of a gradient of concentration of hydrogen ions between matrix of mitochondrias and cytoplasm;

b) Reduction through-membrane electric potential on the internal mitochondrial membrane;

c) Disturbances of АТP-synthesizing enzyme complex;

d) Use of energy of a gradient of concentration of hydrogen ions not on synthesis АТP, but on other purposes (transport of calcium ions from cytoplasm into mitochondria, transport of phosphate, АDP, АТP, etc.).


^ 17.10. Disturbance of what biochemical reactions is accompanied by reducing of АТP synthesis in cells?

Formation of АТP in cells decreases at oppression:

1. Glicolytical (substrate) phosphorylation: substrate-p + ADP substrate + ATP;


2. Oxidizing phosphorylation in mitochondria: ADP + P ATP-syntase ATP + H2O;


3. Creatinkinase reaction: creatinphosphate + АDP P creatin-kinase creatin + АTP;


4. Adenylatecyclase reaction: АDP + АDP adenylate-cyclase АТP + АМP;


5. Nucleoziddiphosphokinase reactions: GТP (UТP, CТP) + АDP nucleoziddiphosphokinase GDP (UDP, CDP) + АТP




^ 17.11. What consequences for a cell are caused with deficiency of АТP?

Deficiency of АТP in a cell leads to:

1) Disturbance of mechanical work - reduction of activity of contractive structures of cells. It is shown by transgressions of elementary cellular functions: contraction, migrations, exo- and endocytosis, cellular division, movement of lash, straps (fig. 59).

2) Disturbance of osmotic work - processes of active transport of ions. At deficiency of ATP mechanisms of primary and secondary active transport suffer: sodium-potassium and calcium pumps, sodium- calcium and sodium-hydrogen exchange mechanisms. It causes disturbances of an endocellular homeostasis and damage of cells.

3) Disturbance of chemical work - biosynthesis of substances. Consequence of it is disturbance of self-recovering and self-reproduction of cells, mechanisms of their long-term adaptation to action of factors of an environment.

Finally there is a slow destruction of cells.

4) Disturbance of reactions of a cellular metabolism.


^ 17.12. What disturbances of a metabolism in cells can be connected with primary deficiency of ATP?

In conditions of deficiency of ATP not only reactions of biosynthesis of substances (anabolism), but also reactions of their splitting (catabolism) are broken.

It is connected with immediate transgression at deficiency АТP such processes as:

- activation of substrates’ (phosphorylation) and their involving into catabolic ways (glucolysis, b-oxidation);

- the activation of many enzymes which is provided by proteinkinase;

- synthesis of cyclic АMP.


^ 17.13. Result examples of "vicious circles" in development of energy deficit conditions of cells.

Reduction of maintenance of АТP in a cell leads to oppression of function of Ca-pumps owing to what concentration of ions of calcium in cytoplasm increases. It causes dissociation of oxidation and phosphorylation - as a result the deficiency of АТP increases.

Insufficiency of АТP in a cell is the reason of its disturbance of protein-synthetic functions. Synthesis of all proteins suffers, and of course synthesis of proteins - enzymes too. It conducts to disturbance of catabolic transformations of nutrients into a cell and processes of biological oxidation - so deficiency of АТP increases.


^ 17.14. What is the basal metabolism?

The basal metabolism - is the minimal power (energy) expenses of an organism defined on morning in a condition of full rest, on an empty stomach (through 12-14 h after last reception of food), in conditions of temperature comfort (t = 18 - 20°С, humidity of air - 60-80 %, speed of its movement - 0,1-0,2 km/s).

^ 17.15. What external and internal factors influence on the level of the basal metabolism?

External factors: climatic conditions; time of day; height above sea level; character of a feed; character of industrial (professional) activity.

Internal factors: growth and weight of a body; the area of a surface of a body; age; a sex.


^ 17.16. Give some examples of increase and reduction of the basal metabolism in conditions of pathology.

The increase in the basal metabolism is characteristic for hyperfunction of a thyroid gland, adenohypophysis, and sex glands.

Reduction of the basal metabolism is registered at hypofunction of thyroid gland, adenohypophysis, and sex glands; during the chronic insufficiency of a bark of adrenal glands at starvation.


18. Starvation


18.1. Define the concept "starvation".

Starvation - is the typical pathological process which arises due to full absence of food or insufficient receipt of nutrients into an organism, and also in conditions of sharp disturbance of structure and assimilation of food.


^ 18.2. How is starvation classified?

According to the origin, physiological, pathological and medical starvation are allocated. Physiological starvation is characteristic for some kinds of animals during winter sleep (marmots, susliks) or summer sleep (reptiles).

According to the maintenance following kinds of starvation are allocated.

1. Complete starvation:

a) Non-absolute - with using of water;

b) Absolute - without using of water.

2. Incomplete starvation (malnutrition) (under-eating).

3. Partial starvation (qualitative).


^ 18.3. From what periods the pathogenesis of absolute starvation with the use of water is consist?

I. The period of uneconomical using of energy.

II. The period of the maximal adaptation.

III. The terminal period.


18.4. How is the period of uneconomical using of energy characterized?

Its duration - 2-4 days .It is characterized by the strong feeling of hunger caused by stimulation (excitation) of the food center. During full starvation it lasts up to 5 days, and then disappears. There is a fast losing of weight of a body (emaciation). The main energy source during this period are carbohydrates that is why the size of respiratory coefficient equals 1,0 . Hypoglycemia arises which intensifies the releasing of glucocorticoids by cortex of adrenal glands. It leads to increasing of protein catabolism in peripheral tissues, such as muscles, and to activation of the glyconeogenesis in a liver.

The basal metabolism increases a little at first, and then gradually reduces and becomes for a 10-20 % less initial one. The negative nitrogenous balance develops.


^ 18.5. What is characteristic for the second period of starvation - the period of the maximal adaptation?

Its average duration is 40-50 days. Rates of reduction of a body weights are slowed down and make 0,5-1 % a day. The feeling of hunger disappears. The main energy source are fats that is why the size of respiratory coefficient equals 0,7 .

Hypoglycemia increases the receipt of lipolytical hormones in blood (adrenaline, glucocorticoids, glucagon). That is why a mobilization of fat from deposits happens - hyperlipacidemia develops .It is the reason of the increasing of ketone bodies synthesis in a liver in its turn. Arising ketonemia can lead to not gas acidosis.

The basal metabolism during this period is 10-20 % less, comparing with an initial level. Nitrogenous balance is negative.


^ 18.6. What is the loss in weight of different organs and tissues in the second period of starvation?

The loss of weight in the second period of starvation makes: a adipose tissue - 97 %, a spleen - 60 %, a liver - 54 %, testes - 40 %, muscles - 31 %, blood - 26 %, kidneys - 26 %, nervous system - 4 %, heart - 3,6 %.


^ 18.7. Give the characteristic of the third period of starvation.

This period is called terminal because it proceeds to death. Its duration is 2-3 days. Intensive disintegration of tissues, intoxication is developed. The main energy source are proteins that is why the size of respiratory factor equals 0,8. Allocation with urine of nitrogen, potassium, phosphates (there are attributes of cells and tissues proteins destruction) increases.

The death comes when reduction of weight of a body becomes up to 50 % of initial.


^ 18.8. What factors define the maximal possible duration of full starvation with the use of water?

1. Endogenous factors: a kind of an animal; age; sex;

Quantity and quality of fats and proteins reserves of an organism;

The general functional condition of an organism; muscular work.

All this factors influence duration of starvation, changing the basal metabolic rate. If the basal metabolic rate is high, the duration of starvation is not long and on the contrary.

2. Exogenous factors. These are factors of the environment which increase energy expenditure of an organism. They are: a low temperature of the environment; high humidity of air; high speed of air flow.


^ 18.9. How is it possible to calculate the maximal duration of full starvation with using of water?

For such calculation it is necessary to remember, that the adult organism dies at loss of 50 % of initial weight of a body and the loss of weight in the second, most long period of starvation makes 0,5-1 % per day.

So, if the initial weight of a body is equals 70 kg the death comes at loss of 35 kg. If the reduction of weight is 0,5 % per day of the initial weight (0,35 kg),than the maximal possible duration of the II period and consequently also starvations as a whole, makes 100 days.


^ 18.10. What is the absolute starvation? What is it features?

Absolute is called starvation without the use of water. Its duration is 2-3 times less, than duration of full starvation with water.

During the absolute starvation there is the increasing of splitting fats for synthesis of the endogen (oxidizing) water therefore ketonemia and non-gas acidosis quickly are quickly developed. The seriousness of the absolute starvation is caused also by accumulation of a great number of terminal products of the metabolism and other toxic products for which removing from an organism water is necessary.


^ 18.11. Name features of incomplete starvation.

Incomplete starvation (energetic deficiency) is developed, when the energetic value of food does not satisfies to energy needs of an organism.

Incomplete starvation from full is distinguished with following features:

1) duration (incomplete starvation can last for months, years);

2) more significant destructive changes in tissues;

3) more significant reduction of the basal metabolism (to a 30-40 %);

4)the development of the significant hypostases(edema) owing to reduction of the maintenance of proteins in plasma of blood;

5) the big losing of weight of a body does not occur because of a delay of a liquid in an organism;

6) it is more difficult to restore an ability to live of systems of an organism after incomplete starvation.


^ 18.12. What is the protein-energetic deficiency? Give some examples.

The protein-energetic deficiency is the condition arising as a result of a combination of incomplete and qualitative protein starvation.

For example:

1. An alimentary dystrophy. It is described in the occupied Leningrad during the Second World War. In its pathogenesis except for the proteins and energy deficiency additional factors also matter: a cold, physical exhaustion, a psychological pressure (stress);

2. An alimentary marasmus. It develops at children till one year. The first place the energetic deficiency acts;

3. Quashiorcore. It develops at children in the age of 3 - 6 years. The main thing in pathogenesis is the protein deficiency. Energetic deficiency is compensated by superfluous consumption of carbohydrates.


^ 18.13. In what clinical syndromes the protein-energy deficiency is shown?

I. The deficiency of protein receipt into organism leads to disturbance of the protein-synthesis function of liver. It is the reason of the hypoproteinemia which, in turn, causes the development of oncotic edemas.

II. The energetic deficiency is the reason of reduction of the basal metabolism. It is shown in decrease of the body temperature (hypothermia).

III. The atrophycal syndromes. Their development is connected with disturbances of plastic and energy supplying of cells.


^ 18.14. By what disturbances of physiological functions are shown the atrophycal changes in organs and tissues during protein-energy deficiency?

The atrophycal changes are developed in all tissues, organs and systems of an organism.

Display of the atrophycal changes in CNS is delay of intellectual development, in digestive system - breaches of the absorption and diarrhea, in cardiovascular system - a hypotension, in immune system - reduction of synthesis of antibodies and increase of sensitivity to infections, in the bone marrow - development of anemia, in skeletal muscles -hypodynamia and muscular weakness, in bones - a delay of growth of a skeleton.


^ 18.15. What is the partial (qualitative) starvation? Name its kinds.

Partial (qualitative) starvation is the deficient receipt of one or several nutrients with food in case of normal energetic value of food. There are such kinds of partial starvation as: protein, fat, carbohydrate, vitamin, mineral, water starvation.

^ 20. Violations of carbohydrate metabolism


20.1. Name the main reasons of violations of carbohydrate metabolism:

1) violation of digestion of carbohydrates and their absorbing in intestine;

2) violation of carbohydrate metabolism in liver;

3) violation of glucose catabolism in peripheral cells (see paragraph 17);

4) violation of the neurohormonal regulation of the carbohydrate metabolism.


^ 20.2. What hormones take part in regulation of the carbohydrate metabolism?

Hormones, that take part in regulation of the carbohydrate metabolism are divided into two groups: insulin and contrinsular hormones.

Hormones which are antagonists of insulin in their biological effects are named contrinsular. They are: adrenaline, glucagon, glucocorticoids, somatotrophic hormone (growth hormone).

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