ELFH Homeostasis Flashcards
Intracellular [K+] is greater than extracellular [K+]
Correct. Intracellular [K+] is about 150 mmoles/L, extracellular [K+] is about 4 mmoles/L.
Under resting conditions in excitable cells, such as nerve or muscle, cell membrane permeability to Na+ ions is greater than the permeability to K+ ions
Incorrect. Permeability to K+ ions is about 20 to 40 times the permeability to Na+ ions.
The net negative charge inside resting cells is mainly carried by chloride ions
Incorrect. Intracellular [Cl-] is much lower than extracellular [Cl-]. The net negative charge is mainly carried on ionised side groups of proteins and on phosphate groups. Neither of these sources of negative charge can exit the cell across the cell membrane.
What is an essential requirement for ATP synthesis?
An adequate supply of oxygen is an essential requirement for ATP synthesis, which primarily occurs within the mitochondria. Metabolism of one molecule of glucose will lead to the synthesis of 36 or 38 (depending on the tissue type) molecules of ATP.
What is the extreme range compatible with life (only for very short time)?
pH 6.9 ↔ 7.8
[H+] 125 ↔ 16 nmoles/L
Acid products of metabolism
The acidic products of metabolism:
Carbon dioxide (CO2) – failure to excrete CO2 adequately leads to respiratory acidosis
Non-CO2 acidic products which include lactate and keto-acids – failure to excrete these products leads to metabolic acidosis
Cell Injury: Stable and permanent cells
Cell injury
Hepatocytes, an example of “stable cells”, can regenerate when driven to re-enter the cell cycle by growth factors produced by surrounding cells.
Neurons and cardiac myocytes, examples of “permanent cells”, have no ability to re-enter the cell cycle and undergo cell division. Dead cells in these tissues may however become replaced by fibrous tissue composed mainly of collagen. This is the basis, for example, for the fibrotic changes which occur in the heart following a period of tissue hypoxia.
Types of cell injury
Types of Cell Injury
Cell membrane damage:
eg complement pathway attack or free radicals
Mitochondrial damage:
eg hypoxia or cyanide poisoning
Ribosomal damage:
eg effects of alcohol on hepatocytes
Nuclear damage:
eg radiation or viruses
Cell death: Apoptosis
Apoptosis
Apoptosis is a physiological event and is often described by terms such as “programmed cell death” or “cell suicide”. This reflects the fact that the cell may itself produce proteins which cause the cell to die. Apoptosis is a very fast process and the whole event may only last a few minutes. As an example, it is a feature of the restructuring of tissues which occurs during embryonic development. A further example is the endometrial cell loss which occurs during the menstrual cycle.
Cell death: Necrosis
Necrosis
Necrosis refers to the series of events which result from cell death occurring in a living tissue. It is a process which involves a large number of cells and it generates a potentially damaging inflammatory response. This may be provoked by the release of cell contents following cell rupture. Necrosis is a slow process.
Why does necrotic tissue swell
Necrotic tissue is inadequately supplied with oxygen and therefore ATP production is limited. Cells need an adequate supply of ATP to maintain ion gradients and therefore water distribution, across cell membranes.
Because the sodium pump expels three Na+ ions for every two K+ ions pumped into the cell, failure of the pump leads to a net accumulation of ions inside the cell. An osmotic gradient therefore develops which means water enters the cell causing it to swell.
Inadequate generation of ATP in a cell leads to osmotic swelling as sodium ions are not expelled fast enough. This is a characteristic of necrotic tissue.
Sodium pump
The concentrations of Na+ and K+ inside and outside cells are (Intracellular: Na 15 K 15 and extracellular Na 140 K 4)
There is a gradient of [Na+] – high outside, low inside the cell and a gradient of [K+] – low outside, high inside the cell. There is therefore a tendency for Na+ ions to enter cells and for K+ to leave cells.
Maintaining the ionic concentration gradients is essential, particularly in the case of “excitable cells”, such as nerves and muscles. The gradients must therefore be maintained by an ATP consuming active pump mechanism
Resting potential of nerves and muscles
A membrane potential is an imbalance in charge distribution across a cell membrane. The actual difference in the number of +ve and –ve charges inside a cell is relatively small compared to the total number of charged species (ions and larger molecules) in the cell.
The membrane potential of excitable cells (skeletal and cardiac muscles and nerve cells) is of the order of -70mV. The negative value means that there is an excess of negative charge inside the cell. In smooth muscle, a typical membrane potential is -55mV and in erythrocytes it is about -9mV. Some key pieces of information to help with the understanding of this topic are as follows:
The distribution of K+ and Na+ ions inside and outside cells is shown in the diagram opposite Nerve and muscle cells are very permeable to K+ ions but, at rest, not very permeable to Na+ ions. Erythrocytes are much closer to equal permeability to the two ions
The negative charge on the inside of cells cannot be attributed to the distribution of Cl- ions. Intracellular [Cl-] is low (20 mmoles/L) compared to extracellular [Cl-] (105 mmoles/L). The excess negative charge inside cells is mainly held on the ionisable side groups of amino acids in proteins and on phosphate groups. These large charged molecules cannot escape across cell membranes
