6th physiopathology lecture:

Sodium (natrium) is the most important extra cellular ion and is an important determinant of
osmolality and permeability.
There is a calculation for calculating the osmolarity if the plasma is almost equal to osmolarity of
extra cellular fluid
This osmolarity of the plasma can be calculated by the concentration of sodium in the plasma
using this formula:
Calculated osmolarity = 2 Na + glycaemia /20 + Urea/3(all in mmol/L)
BUT if the urea/glycaemia is normal then osmolarity can be calculated only by using the
natremia.
The 3 factors (urea, glucose, Na) are important for the osmolarity but for tonicity Na and glucose
are important!
Urea doesnt modify tonicity of space because it diffuses through the space, different amount of
urea can modify the osmolarity but not tonicity.
Sodium and glucose modify both the tonicity and osmolarity
Glucose is the compound which modifies the tonicity and osmolarity of the plasma.
In diabetes mellitus when glycaemia is very increased glycaemia will produce dilution
phenomena.
Meaning in a sample from the patient you will measure glucose, natremia & acid base balance.
If this patient has high glucose it will attract the water from the cell so the natremia here is false
natremia because of the reduced water in the cell and here u have to make measurement for real
natremia.
The ultimate goal in this case should be to buffer the solution to level the acid base, the most
common buffer is sodium bicarbonate but it should be given according to the following:
Over 100 milligrams per deciliter (mg/dL) of glucose Glycaemia
Natremia decreases by dilution with 2.5 meq/L
So that means that this natremia is false decrease (pseudohyponatremia)
For instance:
If the patient has 400 glycaemia that is 300 above the normal so this means that this natremia is
decreased by 2.5 multiplied by 3 that means the natremia must be 140 + 3*2.5
So the natremia will be147.5 meq /L

So in an attempt to re-equilibrate this patient by acid base & electrolyte point of view you
must give him buffer to decrease acidosis but you have to take in account that he already have
enough Na so dont make enough imbalance over his imbalance.
So this was all about dilution effect in hyperglycemia.

NATRIUM
Sodium has many important body functions
- Most abundant extracellular cation along with constituent anion Cl
- regulates osmotic forces therefore regulates water
- very important determinant of osmolarity
- working with potassium and Ca, sodium is important for neuromuscular excitability
- regulates acid base balance
- near sodium chloride is the major anion in extracellular fluid transport following
sodium ,provides electroneutality
The kidney regulates the sodium balance under the influence of some hormone such as
aldosterone delivered by the osmoreceptor signaling done by decreased natrium and increased
potassium which leads to K secretion.
Aldosterone can be also stimulated by the renin-angiotensin aldosterone system by sympathetic
stimulation and decreasing renal perfusion. Renin is secreted by juxtaglomerular cell which
converts angiotensin 1 to angiotensin 2 which have well known effect
ANP and brain Natriuretic peptide and kidney natriuretic peptide
ANP: When the hemodynamic pressure in the atrium is increased this hormone is stimulated and
this fact will decrease the atrial blood pressure
Alteration in sodium chloride and water balance associates changes in tonicity and we have
already discussed dehydration
If we have lots of water, it is never lost alone it is lost with less or more sodium it will be
hypertonic if natremia is increased but hypotonic if its decreased so we can calculate the
deficiency of water in hypertonic and hypotonic dehydration to know how to recover the
imbalance.
The hyper hydration could be hypotonic cud be done by free water in cells, inadequate Na intake
or another important cause inappropriate secretion of ADH secreted by neurophypophysis.
Inappropriate secretion of ADH inhibit urine elimination and water retention cud be done by
brain trauma, surgery pain fear and a form of bronchogenic cancer in this form the cell that
secretes ADH

ADH will inhibit urine excretion and water retention and the extracellular space becomes
hypotonic so we have increased water SO the water have tendency to reestablish the balance of
tonicity establishing cellular hyper hydration and it has effect on tissues such as cerebral tissues
and can have cerebral edema coma

K potassium
Most important intracellular cation
-

Difference between intracellular and extracellular potassium is important

In the functioning of the excitable cell, this Na-K difference is made by the Na-K pump
This pump gives out NA and takes in K
The ratio btw intra and extra K is very important for resting membrane potential. This
potential is important for transmission of electrical impulse in the NM function and in the
cardiac function other function of K it is important for osmolarity in intracellular space
-K is also required for lypogen deposit in skeletal muscle and liver
-k is freely filtered by renal glomerulus and 90% is reabsorbed in the PCT and loop of
henle and in the collecting tubule K is secreted

Factor related to passage transport of K

-1 concentarion gradient at distant and collecting tubules
-2 changes in ph
-3 changes in electrical potential differences across the distal tubule
Factors actively acting on potassium levels

Aldosterone levels it stimulates secretion of K in distal tubules, sweat glands , and in colon
Insulin stimulates the ATPAse pump promoting the K intake in hepatic cell, n promote glu
intake in these cells
Catecholamines increase the K secretion
Beta 2 adrenergic stimulates the movement of potassium into the cells
Alfa adrenergic pathway stimulates the shift of potassium out of the cells

Hypokalemia when potassium concentration is less than 3.5 meq/l in plsma

Causes 1. diuretics
2. by vomiting and diarhoea followed by hypovolemia n aldosterone secration
3. we can also have loss of potassium in the diabetic patient, where we have acidosis
which associates hyperkalemia which is due to exodus of K from the cells but in this situation we

have loss of K through urine cuz the diabetic patient urinates too much, so the total capital of K in
the body is decreased
4. we can have hyperkalemia assoc.. to acidosis
5. we can have hypokalemia by amydylosis
3. in diabetic patient total K is decreased
4. renal losses
5. we can have hypokalemia by mal distrubition of K in extra n intra cellular
compartments for example in the resp and metabolic alkalosis we know abt the shift of K n H ion in
the cell H ion tend to get out of the cell in exchange of K,so alkalosis usually associates hypokalemia
6. alkalosis it will aggravate hypokalemia
7. hyper insulinism this is another possiblty for redistrubition of K in intra cellular and
extra cellular fluid , insulin stimulates the entrance of K into the cells so if insulin is high we ll have
hypokalemia
8. hypokalemia has also some contributing factors to the maintanece of states for instance we can
have loss of K through vegetative fluids like diarrhea , vomiting laxative abuse and so on
9. we dont replace K loss in a balanced manner for example we have reducd intake of K , or if a
patient with K loss associates alkalosis the alkalosis will aggravate the hypokalemia
10 if at the kidney level if wwe have lots o K through some biological process such as Vomiiting n
diarrhea we have also hypovolemia which stimulates the RAAS system ultimately secreting
aldosterone which can lead to some more K loss through kidney
11 use of diuretics
12. if hypokalemia associates low magnesium ,low plasma Mg stimulates renin release which leads
to RAAs system activation and further K loss

PHYSIOLOGICAL CONSEQUENCES OF HYPOKALEMIA

1.it affects neuro-muscular excitability because hypokalemia affects the carbohydrate metabolism
hypokalemia depressed insulin secretion so its a vicious circle and other effect includes on includes
hepatic and skeletal muscle glycogen synthesis
Hypokalemia decrease the neuro muscular excitability cuz cells have rest membrane have a resting
membrane potential of -90 mv and they also have a threshold potential, when the threshold potential
is reached we will have spontaneous depolarization if we have hypokalemia it will affect the level of
resting membrane potential and this difference will be much if the there is big difference in extra
cellular and intracellular potassium level as the ratio between intracellular and extracellular K level is
very important for membrane potential so the resting potential in hypokalemia will be more negative
than normal (to more and more negative values ). The difference between resting and thrshild
potential will be bigger so an usual cant anymore stimulates the cells so the needs much more
strong potential so the exictablilty of cells will decrease sypmptoms musle weakenss, smooth muscle
atrophy intestinal paralysis possibility of ileus , cardiac dysarrythmia with ECG change like
decreased T wave and U wave amplitude , prolonged P wave n so on

These effect of hypokalemia cud be potentiated by hypercalcemia ,if Ca in the plasma is increased
in its concentrations the ca ion will increase the threshold potential it will be more postitive it will
increase the difference between resting membrane and threshold potential so the same the same
effect like hypokalemia but on opposite side so that means if both these modifications occurs at the
same time that means they will have accumulating bad effects prodcung decreased exictabilty og
neural and cardiac cells
2. also effect the renal fun it decreases the ability to concentrate urine if chronic for long term will
produce damage to renal tissue and producing interstitial fibrosis and tubular atrophy
3. cardiac effect

Cause of hyperkalemia
-

Increased intake of K accidental ingestion of K salts, potassiumated Pencillin

Shift of K from the cells metabolic acidosis
Tissue trauma, cell hypoxia , insulin deficiency ,digatilis intoxicity exodus of K from the cells
Other cause renal excretion decreased due to renal failure
Diuretics like spiralolactones

HYPERKALEMIA
Will increase the RESting membrane potential so will short the interval bw resting and
threshold potential leading to higher excitability but with no repolarization leading to higher
neuromusclular excitability
Because of the lack of recovery the cell becomes weaker and ends up in paralysis so the
clinical signs includes tingling of finger n lips, restlessness, diarhoea , intestinal cramps ,
ileus , On ECG we have rrapid repolarization with narrow and taller T waves Short QT
interval Depressed ST segment prolonge PR altered cardiac conduction with V Fibrillation
and finally cardiac arrest
These effects of hyperkalemia cud be accumulated by effects of hypocalcemia,
hypocalcemia will decrease threshold potential leading to increase in the difernce between
Resting membrane and threshold membrane potential but on the other side

DIABETES MELLITUS
Def: is metabolic disease with chronic evolution characterized by disturbances in glucid
metabolism with hyperglycemia or decreased glucose tolerance
Secondary distrurbance lipid and protein metabolisim
All thse phenomema is done by the relative or absolute deficiency of insulin
Classification :
Type 1 : insulin dependent appears in childhood , is characterized by absolute deficiency of
insulin for survival of pat insulin is needed
Genes and automimmunity involved
PATHOGENISIS:

Occurs in childhood or young ,without treatment ketoacidosis leads to coma

Many times pat discovered in coma or coma onset
SYMPTOMS
Polyuria : EXTRA Glucose is excreted through urine, which is osmotic substance leading to
polurea and dehydration which produce adaptive polydypsia
Absolute insulin deficiency causes proteolysis , lipolysios, decreased body weight and will
stimulates center of hunger (polyphagia)
Dysphagia
Polylypsia

Genetic factors and environmental

Genes for potential of DM genes are from the same place which cods for MHC complex
On chromosome 6
HLA-B HLA-15
HLA -1 most common HLA profile for risk of DM
Relation by MHC complex with DM type 1 is auto Immune cuz MHC has 2 clases of
molecules type 1(majority of cell express it ) n type 2 (expressed on APC)
If beta cell MHC type1 ,so the pancreatic cells becomes a APC and intiates auto immune
response
Injured pancreatic cells phagocytized by macrohpages they express MHC 2 sometimes
initates immune response cellular and humoral,so the pancreatic tissue will be destroyed
finally thats why in type 1 DM we have an absolute deficiency of insulin and beta cells are
destroyed
Environmental factors:
1. Viral infections some virus are with tropism such as mumps, rubella ,cocksaxie B
hepatitis cud damage the pancreatic cells
2. Discovering hidden antigens that cud start an response against the pancreatic cells
3. The virus cud have similar antigens from like antigens from pancreatic cells so there wiil
be an cross-immune response like in viral response against pancreatic ag

Type 2 : non Insulin dependent D.M

Adults ,usually 40 years above
Relative defeciancy of insulin , associated with obesity,most patients are obese
In obesity we have hypertrophyof adipose cells more than hyperplasia of the adipose cells
since adipose cells are hypertrophied has a depressed entrance of the glucose and cant take
the glucose from the extra cellular space ,glucose remain in high level in plasma
hyperglycemia which will stimulates the pancreatic secretion so we will have hyper insulinism
insulin which have stayed for a long time in the plasma will start a down regulation for its
receptors in the peripheral tissue so tissue will have depressed expression of insulin which
means insulin resistenace .the simulation of the pancreatic secretion of insulin will end with

Exoexaustion of the pancreas so the insulin production will decrease but not absolute,
relative deficiency of insulin usually continues with insulin resistance ,this ressistenace cud

be quantitative low number of receptors on peripheral cells but also cud be qualitative defect
secondary messenger and defected receptors
Defeiciency of incretins they are intestinal hormones delivered as an response to nutrition
and then effect is increase in insulin response in a glucose dependent manner
1. Glucose dependent insulinotropic polypeptide
Is prod in ileum n colon
Effects
2. Glucation like polypeptide
Produced in jejenum n duodenum
After injection of food these hormone will stimulate the secretion of insulin in beta cell so
food will increase the glucose thse hormone will stimulate the insulin secretion fromthese
cells and
Normal function of thses hormone increase the survival of beta cells cuz they decrease
apoptosis of beta cells and also they favourises the replication of the beta cells
They are used for theraphy and it was noticed their levels was decreaserd in type 2 DM
Sometimes with high success

Secondary D.M (secondary to other endocrine disease)

-hyperthyroisdism , hypercortisolism (influencing insulin ecretion n metabolism)
-pancreatitis (destroyal of beta region )
-medicnal effects diuretics , cortisonic medicine

impaired glucose tolerance after the lunch the level of glucose rises above normal but
normally there is no hyperglycemia

Gestational D.M glucose intolerance appears during pregnancy and disappears after
delivery
Clinical manifestation
Hyperglycemia with its consequences

Hyperglycemia may be seen in some condition like stress, during infection , physical trauma
These people have potential for developing the disease