1.

Regulation of water compartment

Water makes up 60% of our body weight. Out of the 60%, 2/3 is intracellular water and 1/3
is extracellular water. The 20% (1/3) is also subdivided in 15% being inside the interstitial
space and 5% being intravascular (plasma). There is also 1% transcellular water represented
by spinal fluid, eye fluids, joint fluids, pleural fluid.
Water always follows sodium, so during increased osmolarity (concentration of sodium in
blood), water will move from the area of lower osmolarity to the area of higher osmolarity.
Water intake equals with 1500ml from liquids, 700-800ml from semi-solid food and 300ml
from metabolic water. Total water is 2500ml/24h.
Water excretion equals with 1500ml from urine loss, 900ml from sweating and 100ml lost in
stools.
In normal physiological conditions water intake equals with water excretion.
Thirst sensation is stimulated during increased osmolarity. ADH secretion favours
reabsorption of water at DCT.
All digestive fluids are isotonic except pancreatic juice (hypertonic) and saliva (hypotonic).

2. Regulation of electrolyte compartment

In the vessels (extracellular) there is Na = 135 – 145 mmol/L (mEq/L) and Cl = 100 – 110
mmol/L (mEq/L).
Inside the cell (intracellular) there is K = 115 – 140 mmol/L (mEq/L)
Normal osmolarity = 300 – 310 mOsm/L
A) Renin angiotensin aldosterone system activation is the most important electrolyte
regulation. When blood volume is decreased there will be hypoperfusion of the kidney
leading to hypoxia. Renin is synthesised in the juxtaglomerular cells > angiotensinogen >
angiotensin 1 > angiotensin 2 > aldosterone > favourites sodium reabsorption in DCT.
B) Brain natriuretic hormones and atrio-natriuretic hormones are released upon
hypervolemia in the vessels. Decrease in ADH and thirst sensation. Increase in sodium
excretion by inhibiting sodium reabsorption and increasing GFR.

3. Hydro-electrolyte balance – generalities

The balance of this system is maintained by the hydrostatic pressure (45mmHg) which is due
to the electrolytes, and the colloid osmotic pressure (25mmHg) which is due to the
concentration of proteins. The difference between the two maintains an effective filtration
pressure, keeping a normal glomerular filtration. Interference between the balances of these
two parameters, water will leave the vessels and cause edema.

4. Sodium alteration during hydro-electrolyte disturbances

Increase of sodium in the vessel leads to an increase in osmolarity = > 310 mOsm/L =
hypertonic
Decrease of sodium in the vessel leads to a decrease in osmolarity = < 290 mOsm/L =
hypotonic
Normal sodium in the vessel = isotonic
5. Hypertonic dehydration
Sodium is increased meaning osmolarity is increased and water concentration in vessel is
decreased. Water will leave the cells and enter the vessel leading to cellular dehydration and
triggers a thirst sensation. Causes are:
A) Deficiency of intake:
- Coma, patient cannot say he is thirsty
- Esophageal tumours, obstructing passage of solids and liquids causing dehydration
- Tetanus, patient has trismus (lock-jaw)
- Rabbies, become agitated by sound of water and refuse to drink
- Deglutition problems
B) Exaggerated fluid loss:
- Central diabetes insipidus, decreased ADH leading to polyuria
- Diabetes mellitus, in hyperglycaemia water follows glucose in urine leading to
polyuria and polydipsia (excessive thirst)
- Exaggerated sweating, sweat is hypotonic

6. Isotonic dehydration
The patient is losing water and electrolytes in the same proportion therefore there is normal
osmolarity. Patient will be thirsty but no due to an osmotic effect but rather from a decrease
in blood volume that will excite baroreceptors and activate thirsty centres. Causes are:
- Acute haemorrhage
- Burns (plasma loss)
- Vomiting, diarrhoea
- Ascitis
7. Hypotonic dehydration
Osmolarity in the vessel is decreased. Inside the cell osmolarity is normal so the water from
the vessel will go inside the cell causing cellular hyper-hydration with no thirsty sensation
and cellular edema. Causes are:
- Addison disease, decrease of aldosterone leads to a chronic decrease of sodium
reabsorption.
- Urinary tract obstruction, obstruction will cause fluid to accumulate which is rich in
salt, upon removal this hypertonic fluid will be lost
- Different types of glomerular disorders (nephritis), salts are lost
- Loop diuretics

8. Hypertonic hyper-hydration
There is an increase in the osmolarity inside the blood vessel and an increase in water. The
higher osmolarity of the blood vessel will cause water from the cell to enter the vessel
leading to sensation of thirst. It further causes extracellular hyper-hydration and intracellular
dehydration. Causes are:
- Drinking sea water, salt water is hypertonic
- Hyperaldosteronism, adrenal glands produce too much aldosterone and too much
sodium and water that follows it will be reabsorbed.
- Patients in coma, due to hypertonic fluids
9. Isotonic hyperhydration
There is normal osmolarity everywhere but water is increased and cannot move anywhere.
Too much water in vessels is a generalized edema.
In hypoproteinemia due to liver cirrhosis for instance, the patient has a decrease in albumin
synthesis (decrease of colloid osmotic pressure). Water leaves the vessel and causes edema
> leading to hypovolemia > renal hypoperfusion > renal hypoxia > activation of RAAS
Due to increased water in the vessels the hydrostatic pressure increases like in congestive
heart failure.
Nephrotic syndrome or liver failure leads to a decrease in colloid osmotic pressure.
Edema is always caused due to a difference between hydrostatic and colloid osmotic
pressure.

10. Hypotonic hyper-hydration

There is a decreased osmolarity in the vessel and an increase of water so water will leave the
vessel > edema. Causes are:
- Tumours of posterior pituitary gland, increased ADH secretion cause excessive water
reabsorption without sodium.
- Diabetes insipidus
- Increase intake of hypotonic fluids
- Coma, due to the hypotonic fluids and the lack of excretion
- Drinking beer

11. Acid-base balance – generalities

Normal pH = 7.36 – 7.44
Normal PCO2 = 36 - 44 mmHg
Normal concentration [HCO3-] = 22 – 27 mEq/L
Normal concentration [H+] = 38 – 42 nEq/L
pH < 7.36 = acidosis
pH > 7.44 = alkalosis
H2CO3 (carbonic acid) appears every time when a certain metabolization of a substrate will
be complete.
Incomplete metabolization of fats will lead to excessive production of beta-hydroxybutyric
acid and acetoacetic acid, which are non-volatile acids.
Incomplete metabolization of carbohydrates will produce lactic acid due to ischemic
conditions or anaerobic conditions.
The acid-base balance is maintained by the lungs, the kidneys, the HCO3-/H2CO3 buffer
system and the Hgb buffer system

12. Mechanism of pH regulation

Carbonic acid is unstable and can break down into water, HCO3- and H+ under the action of
carbonic anhydrase.
H+ can be bound or released, making the blood more alkaline or acidic respectively.
Excessive CO2 can be released by hyperventilation.
Excessive HCO3- can be excreted by urine; normally it is reabsorbed to 99%.
 A) Protein buffer system
- Proteins have side chains which can buffer hydrogen ions
- Hgb is an ideal buffer because it not only binds H+ but also CO2
B) The lung buffer system
- The lungs regulate p[CO2] by hyperventilating = more carbon dioxide is released,
decreasing the partial pressure of carbon dioxide resulting in an increase in pH.
- By hypoventilating = less carbon dioxide is released, increasing the partial pressure
of carbon dioxide resulting in a decrease of pH.
C) The kidneys
- They regulate hydrogen ion excretion and bicarbonate reabsorption.
- Bicarbonate is filtered by glomerular filtration.
- Usually 90% of the bicarbonate is reabsorbed in the lumen of PCT by the help of a
sodium-hydrogen antiporter  sodium is transported out of the tubular cells in
exchange for hydrogen ions. These H+ ions then bind to HCO3- by carbonic
anhydrase, which is an unstable acid and changes into H2O + CO2, inside the
cytoplasm of the tubular cells. The carbon dioxide then diffuses into the cell and
dissociates with water back to its original substrates, H2CO3, which will further
dissociate into H+ + HCO3-, then the bicarbonate can leave the cell and enter the
blood, whole H+ will enter in the lumen of tube. The bicarbonate can then leave he
cell via different mechanisms.  the urine in bicarbonate free.
- 10% in the DCT, bicarbonate is secreted into the lumen either in exchange for Cl- or
H+ through a proton pump. Most of the hydrogen ions can be bound to NH3 forming
NH4+ and thereby prevents an acidosis.

13. Compensatory mechanism during acid-base disturbances

Respiratory alkalosis (decreased partial pressure of carbon dioxide) = decrease in
concentration bicarbonate to compensate.
Respiratory acidosis (increased partial pressure of carbon dioxide) = increase in
concentration of bicarbonate to compensate.
Metabolic alkalosis (increased concentration of bicarbonate) = hypoventilation (increases
partial pressure of carbon dioxide).
Metabolic acidosis (decreased concentration of bicarbonate) = hyperventilation (decreases
partial pressure of carbon dioxide).

14. Metabolic acidosis

pH is less than 7.35, or normal but at the lower
HCO3  22
PCO2 
Compensation:
Lung  hypoventilation
Mechanism affected is bicarbonate which is decreased. The buffer system will try to reduce
it and if the acidosis persists the second line of defence will act upon respiratory system
causing hyperventilation (Kussmaul respiration).
Causes are:
A) Due to increased endogenous acid production
 - Diabetes mellitus, there is an excessive production of fatty acids or ketone bodies,
which are non-volatile acids. Daily we have a small amount of non- volatile acid
production, but these are neutralised. If there is a decreased amount of insulin then
(diabetes mellitus) for 48 hour it will be enough energy from glycogen, but after the
energy will come from other sources then carbohydrates: fats and proteins but their
metabolization will be incomplete  non-volatile acid accumulation (beta
hydroxybutiric acid and acetoacetic acid) and their excess production will consume
bicarbonate. The bicarbonate will try to buffer the ketone bodies but eventually will
not be able to maintain homeostasis leading to Kussmaul respiration. pH will be
normal but bicarbonate will be decreased. Metabolic acidosis always could lead to
ketoacidosis.
- In case if someone has a physical effort meaning that there is an excess production
of lactic acid (in anaerobic conditions) which won’t be metabolized properly which
will lead an accumulation  increased consumption of bicarbonate  metabolic
acidosis.
- Exogenous excess intake of acid substances, suicide by methanol, excess aspirin.
B) Due to increased bicarbonate excretion
- Proximal tubular acidosis, because the bicarbonate is reabsorbed there, which will
lead to loss of bicarbonate  metabolic acidosis.
- Diarrhoea

Analysis: It can be glucose and ketone bodies in urine.

15. Metabolic alkalosis

pH will be above 7.44, or normal. Bicarbonate values will be increased. Hypoventilation will
result as a compensatory mechanism.
Causes are:
- Milk alkaline syndrome, milk neutralizes gastric acid so patient will be happy for a
few hours. However, there will be a rebound effect of increased hydrogen ions
productions afterwards.
- Exaggerated intake of sodium bicarbonates, like anti acids, too much intake of
alkaline substances
- Duodenal ulcer
- Vomiting, loss of gastric juice
- Distal tubular acidosis, loss of hydrogen ions through urine.

16. Respiratory acidosis

pH is acidic, or it can be normal but at the lowest level of normal, if the compensatory
mechanisms are working properly. Partial pressure of carbon dioxide is increased.
pH ≤ 7.36
pCO2 > 40 mmHg
HCO3 ↑ ( more than 24 mEq/L )
Compensation:
Kidney  There is increased reabsorption of bicarbonate and increased excretion of
hydrogen ions. Only after 24 hours and usually compensates totally the disbalance.
 Lungs  Instantly but not that strong as kidney.
Causes are:
- Coma, patients have trouble breathing
- Drug abuse
- Lung diseases ( COPD, Pulmonary emphysema, asthma is NOT, rib fracture)
- Congenital heart diseases
- Myasthenia gravis
Parameters for diagnosis:
- pH checking, either normal or decreased.
- pCO2
- urine is acidic, normally pH 4-8
Treatment:
We have to treat the initial problem. If the patient has COPD, an old one, whose lungs are
almost out of function, who has a chronic hypoxia and the patient is cyanotic. If we are
giving high O2 under high pressure we can stop the activity of the respiratory centre. The
mechanical ventilation is more useful.

17. Respiratory alkalosis

pH is increased, or normal
pCO2 ≤ 38 mmHg (in case of hyperventilation)
HCO3  (less than 22 mEq/L)
Compensation:
Kidney  It will be a decrease in bicarbonate reabsorption and an increase of hydrogen ions
reabsorption as compensatory mechanisms.  Alkaline urine.
Causes are:
- Physical effort
- Meningitis, encephalitis (diseases which affect the brain)
- Stress like fear, scare felling, emotion which leads to hyperventilation
- Hysteria, excess emotion, panic attack
- Hypocalcaemia, leads to tetany that causes hyperventilation

18. Potassium homeostasis

Potassium is the most important electrolyte inside the cell, it maintains resting cell
membrane potential, heart muscle contraction, involved in enzymatic reactions and protein
synthesis.
Cellular concentration: 150 mEq/L
Vascular concentration: 3.5 – 5 mEq/L
A) External balance
- Daily intake of potassium is 100mEq
- 100% of filtered amount is reabsorbed, 50 – 60% in PCT, 30 – 40% in loop of Henle
and the rest in DCT.
- Total potassium in urine is due to excretion in collecting duct and depends on
amount present in tubular cells, urinary flow and mineral corticosteroids like
aldosterone concentration
B) Internal balance, movement of potassium inside the cell
 - Sodium – potassium ATPase, potassium ions enter cell and sodium ions leave the
blood vessel
- Insulin, favorises entry of potassium ions inside the cell and may lead to
hypokalemia
- Alpha – adrenergic stimulation, increases extracellular potassium concentration
leading to hyperkalemia
- Beta – blockers increase vascular potassium, keep potassium ions inside the cell lead
to hypokalemia

Acidosis causes hyperkalemia because potassium ions leave the cell to maintain
electrical balance. Alkalosis causes hypokalemia.

19. Mechanism of hypokalemia

A) Internal balance disturbance, movement of potassium ions across the cell membrane
- Alkalosis, hydrogen ions enter blood vessel while potassium ions enter cells
- Beta – adrenergic stimulation, sends potassium ions inside cells
- Excessive insulin, favours potassium inside cells
B) External balance, intake/excretion
- Deficiency of intake
- Chronic diarrhoea or vomiting, hydrogen ions are lost leading to alkalosis
- Renal losses due to hyperaldosteronism
- Diuretics, favours potassium excretion by increasing aldosterone concentration

ECG manifestations are flattened T waves and U wave (right after T wave).

20. Mechanism of hyperkalemia

Heart problems appear at concentration of K+ above 6 mEq/L. Potassium is released from
damaged red blood cells in a blood sample, this is false hyperkalemia.
A) Internal balance disturbance
- Acidosis, hydrogen ions leave blood vessel and enter cell while potassium does the
opposite.
- Diabetes mellitus, with keto-acidosis.
- Low insulin, insulin favours potassium to enter cells
- Exaggerated use of beta-blockers, inhibit potassium movement inside the cell
- Alpha adrenergic stimulation, favours potassium to enter vessels
B) External balance disturbance
- Exaggerated intake of potassium (IV perfusion)
- Chronic renal failure, decreased excretion of potassium
- Potassium penicillin iv infusion
- Addison disease, less aldosterone meaning less potassium is excreted
- Decreased level of renin means potassium excretion is decreased

ECG manifestations are peak T waves, flattened P waves, wider QRS complex and
prolonged PR interval.

21. Calcium homeostasis

99% of calcium is in the bones.
 Normal value = 8.5 – 10.5 mg% in blood or 2.1 – 2.6 mEq/L
Normal diet contains 800mg/24h of calcium, mainly from dairy products.
50% of calcium is ionised [Ca2+], responsible for heart activity, neuromuscular activity and
vascular activity
40% is protein bound by albumin
10% is found as organic combinations
A) Parathyroid hormone
- Increases calcium ions concentration
- Reabsorbs calcium from bones and kidney
- Favours hydroxylation of 25 hydroxy vitamin D in position 1
- In order to absorb calcium, vitamin d is hydroxylated in position 25 in liver and
position 1 in kidney
B) Calcitonin
- Reabsorbs calcium in kidney but stores calcium in bones
- Decreases blood calcium levels
C) Calcitriol (1-25 vit D)
- Favours digestive reabsorption in duodenum of calcium

22. Mechanism of hypocalcaemia

When calcium is <2.1mEq/L
Causes are:
- Decrease in intake of dairy products
- PTH deficiency
- Irradiation of PTH
- Resistance of cell to PTH
- Drugs inhibiting PTH
- Decreased magnesium, PTH cannot be released into circulation in the absence of
magnesium
- Vitamin D deficiency
- Renal or liver diseases, deficiency of vit D hydroxylation

23. Mechanism of hypercalcaemia

When calcium is >2.6mEq/L
Causes are:
- Parathyroid carcinoma, excessive production of PTH, leads to osteoporosis over time
- Malignant diseases that produce hormones with similar effect to PTH
- Increased production of calcitriol

24. Consequences of hypocalcaemia and hypercalcaemia

Neurological consequence is tetany (spasm). CHVOSTEK’s sign is percussion of muscle
innervated by facial nerve and there will be spasm of opposite lip. TROUSSEAU sign is cutting
blood pressure and arm and hypocalcaemia will induce muscle spasm.
 Hypercalcaemia causes muscle disturbance and muscle weakness

25. Phosphate homeostasis

600 grams distributed all over the body
Phosphorus absorbed in the jejunum, favoured by calcitrol
Normal values = 0.8 – 1.4 mosmol/L
Renal reabsorption is inhibited by PTH by reducing the amount of transporters at the surface
of cells.
Normal intake is 900mg/24h, excretion 300mg in faeces and 600mg in urine.

26. Mechanism of hypophosphatemia

Causes are:
- Insufficient calcitrol
- Duodenal ulcer, milky solution taken by patient favours digestive excretion of
phosphorus
- Increase in PTH, it blocks reabsorption of phosphorus in the PCT
- Fanconi’s syndrome, blockage of glucose, phosphates and amino acids in PCT

27. Mechanism of hyperphosphatemia

Causes are:
- Acute renal failure, deficiency in the excretion process
- Chronic renal failure, phosphorus can’t be excreted anymore so PTH maintains its
level
- An exaggerated intake

28. Consequences of hypophosphatemia and hyperphosphatemia

Hypophosphatemia = deficiency of phosphorylation causing decrease in G6PD activity
leading to haemolytic anaemia. Also, there is less ADP and ATP, meaning less energy through
cells.
Hyperphosphatemia = makes inorganic complexes with calcium causing hypocalcaemia and
can cause all sorts of blocks. Acute renal failure can also happen.

29. Magnesium homeostasis

Magnesium is a cofactor for more than 3000 reactions
Normal value = 0.8 – 1 mEq/L
55% ionized, 30% protein bound, 15% organic complexes
PTH and vitamin d3 favour magnesium reabsorption while it is inhibited by an increased
calcium level.
Magnesium can bind to calcium receptors and may exert their effects.
The average adult has 24g of magnesium in their body. 60% stored in bones, 40% in body
cells and 1% in extracellular fluid
Normal serum concentration is 1.8 – 2.7 mg/dL

30. Mechanism of hypomagnesaemia and hypermagnesaemia

A) Hypermagnesaemia
 - Magnesium sulphate, used to treat hypertension crisis, causes severe vasodilation
which results in decreased blood pressure
- Treatment of diseases using magnesium
B) Hypomagnesaemia
- Rarely due to diet intake
- Excessive calcium intake, impairs intestinal absorption of magnesium by competing
for the same site
- Alcoholics, they prefer to drink than to eat
- Diarrhoea, vomiting
- Loop diuretics
- Antibiotics like gentamicin
- PTH deficiency since it favours magnesium reabsorption in ascending loop of Henle

31. Consequences of hypomagnesaemia and hypermagnesaemia

Hypomagnesaemia = Personality changes, tetany, tachycardia, hypertension, cardiac
dysrhythmias
Hypermagnesaemia = Lethargy, confusion, coma, hypotension, cardiac arrest, cardiac
dysrhythmias

32. Extravascular haemolysis

Red blood cells are coated with antibodies or have an abnormal shape of membrane and are
attacked prematurely by the liver and spleen phagocytes. The engulfed haemoglobin is
converted to iron for recycling and the globin portion becomes bilirubin later on.
Exaggerated haemolytic anaemia leads to jaundice:
- Megaloblastic anaemia
- Spherocytosis (missing protein spectrin)
- Sickle cell anaemia
- Beta-thalassemia
- G6P deficiency

All lead of increased production of unconjugated bilirubin

33. Jaundice – increased production of bilirubin

- Exaggerated haemolysis, during haemolytic anaemia
- Reabsorption of different hematomas
- Ineffective erythropoiesis (lack of vit b12)
- Transfusion of old blood

Hepatocytes can increase 6 times the ability to conjugate bilirubin but sometimes the
released amount is exceeded.

34. Jaundice – decreased uptake and conjugation

- Improper uptake from small sinusoidal vessels.
- Ligandin deficiency, once introduced in the hepatocytes the unconjugated bilirubin
has to be bound by ligandin.
- If UDP-GT (glucoronyl transferase) is affected, there will be no conjugation
35. Jaundice – intra and extra hepatic obstructions
- Choledocholithiasis, small stone obstructing the common bile duct. Accumulation of
conjugated bilirubin inside the blood.
- Pancreatic head tumour, obstructs the main biliary channel
-
36. Mechanism and consequences of portal hypertension
The fibrotic nodes in liver cirrhosis will compress the small vessels, increasing the pressure
inside the portal circulation (normal 7 – 10 mmHg)
Consequences are:
- Collateral circulation between portal and inferior vena cava circulation >
haemorrhoids in anal region
- Shunt between portal circulation and splenic circulation > splenomegaly
- Shunt between portal circulation and superior vena cava > oesophageal varices

37. Hepatic encephalopathy

Due to collateral circulation, liver is bypassed and some substances supposed to be
neutralized (urea, creatinine, ammonia, gamma amino butyric acid) lead to a hepatic
encephalopathy which is a reversible alteration of nervous system during liver cirrhosis or
other serious disorders. Substances exert their toxic effects upon the brain. Strict diet is
needed, and antibiotics that act strictly inside the intestine.

38. Hepato-renal syndrome

It is an irreversible vasoconstriction affecting cortical area of the kidney, the GFR will be
decreased, and the urinary flow will be decreased. Usually patients are dying they have a
mix hepatic and renal coma. A liver transplant may improve renal condition. The constriction
is due to some toxic product that are not neutralised.

39. Investigations of liver function

In order to have pathological manifestations a big part of liver should be out of function,
because liver has a high regenerative ability.
- Decrease of total serum protein based on decrease of total albumin then
electrophoresis.
- Clotting factors 2, 5, 7, 9, 10, are synthesised inside the liver under the action of
vitamin K, check prothrombin/quick time  which will show us the activity of
prothrombin factors 2, 7, 9, 10. Clotting factors 11, 12 & fibrinogen are also
synthesised in liver.
- In serious liver failure, fibrinogen is decreased.
- If cholinesterase but this is so hard to be determined so we check
pseudocholinesterase, which is decreased, liver function is very affected.
- In case of a serious liver disorder for example hepatocytolytic syndrome which leads
to the destruction of hepatocytes there could be some alteration in number of some
substances which are located in the liver: ALT (alanine-amino transferase) and AST
(aspartate-amino transferase) concentration increases when hepatocytes are
destroyed. If ALT is increased it can be only in some simply permeability problems, is
 not necessary to have a serious liver disorder. When AST is increased this show a
serious destruction of liver.
- Other substances located in the hepatocytes: Vitamin B12, iron maybe
- Increase in conjugated bilirubin indicates obstruction  Bilio-obstructive syndrome.
Unconjugated bilirubin ↑↑. If there is a serious destruction of hepatocytes both
fractions could be increased. **Everyday approximately 250ml of blood is
haemolysed, and it will release an important amount of bilirubin, unconjugated
bilirubin. Which is not soluble in water so it has to be carried by albumin into the
hepatocytes. Once is in inside it has to be bound by another protein called ligandin
then it waits the action of another enzyme uridine diphosphate glucoronid
transferase which will convert unconjugated bilirubin into conjugated and it will be
excreted into the biliary pole from the hepatocytes and it will enter to the
duodenum, where it will suffer the actions of some bacteria and will became 
urobilinogen. Part of it will enter to the hepato-entero circulation, part of the will be
excreted through urine and part will stay in the intestine transformed into
stercobilinogen and will be excreted through faeces.
- Gamma glytamyl transpeptidase, 5-nucleotidase, leucine amino peptidase help
diagnose jaundice. If its increased it means that there is a biliary obstruction.

40. Alterations of digestive motility

A) Oral phase
- Voluntary time, bolus is collected at back of the mouth is that it can be lifted by
tongue.
B) Pharyngeal phase
- Non voluntary time, soft palate and palatopharyngeal folds are pulled so that food
doesn’t enter nasopharynx. Vocals cords and epiglottis cover the larynx.
- Respiration is inhibited and constrictive movements of the pharynx move the bolus
into the oesophagus.
C) Oesophageal time
- Oesophageal muscle contractions help carry the bolus from upper oesophageal
sphincter to lower oesophageal sphincter.

41. Deglutition disorders

Local inflammation will affect buccal time + pharyngeal time like in tonsillitis.
- Achalasia, improper relaxation of the lower esophageal sphincter
- Permanently contracted lower oesophageal sphincter
- Diffuse oesophagus spasm
- Dysphagia (difficulty swallowing), odynophagia (painful swallowing) due to
narrowing of oesophagus
- Oesophageal stenosis, narrowing of oesophagus lumen
- Cancer of oesophagus
- Oesophageal atresia, no connection between oesophagus and stomach
- Varices of oesophagus, secondary to liver cirrhosis
- Diverticular disorders
- Foreign bodies swallowed by children
42. Gastric motility – physiology
Motility of the stomach is the churning and grinding of solid food.
Food will go from oesophagus into proximal stomach > receptive relaxation (15 – 20s).
Container will adapt to the size of ingested food. During this phase the gastric juice mixes
with food and it becomes chime and is sent to distal stomach (3 -5 contractions/min with
duration 2 – 20s). Arrived at pylorus, there will be pyloric and antrum contraction that sends
1- 4ml into duodenum (here there are 12 contractions/min).

43. Gastric motility – alterations

A) Hyperkinetic/hypertonic stomach
- Too many contractions, due to hypersecretion of gastric juice
- During gastritis, due to increase gastric secretion (parasympathetic system also
increases secretion)
- Exaggerated motilin production
- Zollinger-Ellison syndrome (ZES), multiple duodenal and pancreatic ulcers,
exaggerated secretion
- Gastric reflex reaction
- Gastrinoma, tumour secreting excess gastrin which increases gastric secretion
- Stress (histamine secretion) and dumping syndrome
B) Hypokinetic/hypotonic stomach
- Vagotomy, parasympathetic system is affected
- Gastric atony, leads to gastric retention
- Pyloric stenosis, leads to stomach dilation and induce vomiting
- Uncompensated diabetes mellitus

44. Intestinal motility

There will be slow movement in small intestine to avoid bacterial proliferation. There is also
a relaxation of 46min.
Accelerated peristaltic movement happens when there is an increased bacterial proliferation
or inflammation of the small intestine. This is due to increased carbohydrate intake or stress.
Decreased motility of the small intestine is due to excessive fat intake, enteritis and physical
effort.
Large intestine produces haustrations (local digging-type action ensuring faecal mass is
entirely exposed to intestinal surface) and propulsive mass movements.
During constipation, tumour or diverticuli there is decreased motility.
During inflammation such as Cohn’s disease and ulcerative colitis there is increased motility.

45. Alterations of salivary secretions

1.5L of saliva produced in 24h.
Hypersalivation (ptyalism) can by physiological due to activation of some receptors or
pathological.
Pathological hypersalivation is found in smokers, Parkinson disease, inflammation of mouth
and pharynx, epilepsy, hypersecretion of gastric juice.
Swallowing saliva affects gastric pH since it is alkaline.
 Hyposalivation can be physiological due to medication taken or dehydration (temporary).
There are 2 syndromes leading to permanent hyposalivation:
- Sjogren’s syndrome, a systemic autoimmune disease in which immune cells attack
and destroy the exocrine glands that produce tears and saliva
- Qualitative alteration where composition of saliva is affected such as in poisoning
with lead and mercury or viral infections.

46. Regulation of gastric secretions

Stomach has cardiac, pyloric and fundic glands. Fundic glands are made of mucous neck
cells, chief cells, enterochromaffin like cell, parietal cells (produce HCl and intrinsic factor
responsible for vit b12 metabolism).
A) Hyperchloridia (hyperacidity) is increase production of HCl due to:
- hyperproduction of gastrin or histamine
- Action of prostaglandins (vasodilation and proper irrigation of gastric mucosa)
- Some drugs inhibit prostaglandins, inhibiting COX (cyclooxygenase)
B) Hypochloridia (hypoacidity) is anything leading to destruction of parietal cells of gastric
mucosa due to:
- Autoimmune destruction
- Gastric atrophy
- Gastrectomy
- Achloridia (no production of HCl)

47. Pancreatic and biliary secretions

Cholecystokinin (duodenum and jejunum) is released into blood and binds to pancreatic
acinar cells, ordering them to secrete large quantities of digestive enzymes. Contracts gall
bladder and stimulates it secretion. Increase pancreatic bicarbonate secretion.
Secretin (duodenum) stimulates duct cells to secrete water, bicarbonate and juices.
Gastrin (stomach) stimulates pancreatic acinar cells to secrete digestive enzymes.

48. Gastrointestinal hormones

- Gastrin inhibiting polypeptide (GIP), inhibits HCl secretion in pancreas
- Pancreatic polypeptide, inhibits pancreatic secretion
- Motilin, favours GI motility
- Antero-glucagon, hyperglycemiant hormone
- Prostaglandin, vasodilation that helps proper irrigation of gastric mucosa

49. Gastrointestinal hormones – candidates

- Somatostatin, inhibits everything, including its own production
- Histamine, increases vasodilation through H1 receptors and production of HCl
through H2 receptors.
- Vasoactive intestinal polypeptide (VIP), favours production of intestinal juices and
can induce pancreatic cholera (watery diarrhoea)
- Bombesin, stimulates production of gastrin
- Ankephalin, contraction of the sphincter, relaxation of smooth muscle, and
production of gastric and intestinal juice.
50. Glomerular functions – generalities
It is a bundle of capillaries between an afferent arteriole and an efferent arteriole to have
protection during pressure variations.
The capillaries of the glomeruli are supported by a stalk of mesengial cells (play the role of
smooth muscle and are affected by different hormones) and a basement membrane.
Glomerulus is made of three layers: capillary endothelium, basement membrane and
epithelial layer (podocytes).
The functions of the glomerulus are filtration (only small substances can pass through and
180L of blood are filtered every day), reabsorption and secretion.
Glomerular filtration rate (GFR) = 100 (+/-25)
Inulin is best substance for clearance rate.
Renal plasmatic flow = 650 – 750ml
During increased blood pressure, there is vasoconstriction of afferent arteriole to protect
against the high pressure. During low blood pressure, there will a vasodilation of the
afferent arteriole and a vasoconstriction of the efferent one.

51. Glomerular disorders – immunological mechanism

Glomerulonephritis, streptococcal infection, reaction can happen straight in basement
membrane with fixed glomerular antigen or in the circulation with immune circulating
complexes.
Antigens can be of endogenous origin (viral hepatitis) or exogenous origin (poststreptococcal
membrane)

52. Glomerular disorders – vascular and metabolic mechanisms

Involve and increase in permeability of the glomerulus.
More than 3.5g of protein in urine is nephrotic syndrome
Nephrotic syndrome leads to hypoproteinemia > decrease in colloid osmotic pressure >
water leaves the vessels > renal hypoperfusion > activation of RAAS > reabsorption of
sodium. This causes edema.
The increase of protein production in the liver to replace those which are lost will lead to
hypercholesterolemia because of overproduction of apoprotein–100. Impure nephrotic
syndrome has arterial hypertension, will pure one doesn’t have.
Nephritic syndrome = collection of signs associated with disorders affecting the glomeruli.

53. Consequences of glomerular disorders

There are alterations in the permeability of basement membranes.
- Goodpasture syndrome, antiglomerular basement antibody disease
(glomerulonephritis and lung haemorrhage).
- Enzymes and toxins are released by monocytes, neutrophils and lymphocytes that
damage the membrane.
- Diabetes mellitus, end stage renal disease (chronic renal failure)
54. Homeostasis of tubular functions
Most substances filtered are reabsorbed in the PCT: glucose, amino acids (mostly),
phosphates (mainly), Sodium (99%), bicarbonate (85%), potassium
DCT reabsorbs substances that weren’t entirely reabsorbed before: sodium (1%) under
action of aldosterone, hydrogen and potassium ions excreted
In collecting duct water is reabsorbed under the action of ADH

55. Tubular-interstitial nephritis – functional disorders

The structure is maintained but function is altered.
- Type 2 renal tubular acidosis, affects PCT in that it fails to reabsorb bicarbonate
- Fanconi syndrome, glycosuria, amino aciduria, phosphaturia and bicarbonaturia
- Type 1 renal tubular acidosis, hydrogen ions cannot be excreted in the DCT
- Type 4 renal tubular acidosis, decrease production of aldosterone causes
hyperkalemia in DCT
- Central diabetes insipidus due to lack of ADH
- Nephrogenic diabetes insipidus, cells of the kidney don’t react anymore

56. Tubular-interstitial nephritis – organic disorders

Function as well as the structure is altered.
- Acute or chronic pyelonephritis, infection of upper urinary tract
- Acute tubulo-interstitial nephritis (leucocytes and urinary disturbances)
- Chronic tubulo-interstitial nephritis, following acute one if untreated. Also caused by
exaggerated use of analgesics.

57. Acute renal failure – definition and generalities

It is a sudden or brutal suspension of the kidney functions (filtration, reabsorption an
excretion) which is potentially reversible.
Acute renal failure may be attended with oliguria, anuria or even polyuria.
Renal plasma flow = 650 – 750ml
25% of cardiac output goes to kidney
Glomerular autoregulation
- angiotensin 2 = powerful vasoconstrictor
- epinephrine = vasoconstrictor
- prostaglandins = vasodilator
- thromboxane A2 = very important vasoconstrictor during obstructive disorders
- atrial natriuretic peptide = vasodilates afferent arteriole and constricts efferent one

58. Acute renal failure – pre-renal

It is a sudden and severe drop in blood pressure (shock) or interruption of blood flow to the
kidneys due to a severe injury or illness.
Causes are:
- Hypovolemia, following acute haemorrhage, dehydration, intensive diarrhea, burn
injury
 - Distributive shock, anaphylactic (intensive vasodilation), septic shock (toxic agents
that lead to intensive vasodilation)
- Cardiogenic shock, myocardial function
- Decreased renal perfusion, due to vasoactive mediators, drugs, diagnostic agents
- Diabetes insipidus

59. Acute renal failure – intrinsic

It is the direct damage to the kidneys by inflammation, toxins, drugs, infection, or reduced
blood supply.
Causes are:
- Acute glomerulonephritis post-streptococcal
- Acute pyelonephritis
- Acute tubular necrosis (ATN), due to aggressive action of some drugs or even a
massive infection

Treatment is dialysis, stop aggression of the drug in ATN and monitorize continuously
potassium ions.

60. Acute renal failure – post-renal

It is the sudden obstruction of urine flow due to enlarged prostate, kidney stones, bladder
tumour, or injury.
Causes are:
- Bilateral ureteral obstruction
- Prostatic problems, prostatic hypertrophy compresses the urethra
- Bladder problems, tumour, neurogenic bladder
- Retroperitoneal fibrosis (Ormond disease), fibrous tissue forms behind stomach and
intestines which blocks the intestines
- Bilateral hydronephrosis, urine cannot drain down the ureters.

Only treatment is ablation, removal of the obstacle.

61. Chronic renal failure – definition and generalities

It is a progressive and irreversible destruction of the structure of the kidney. The kidney
cannot maintain homeostasis anymore leading to end stage disease. Most important
disorders responsible are diabetes mellitus, hypertension, and glomerulonephritis.
As kidney structure is destroyed, remaining nephrons undergo structural and functional
hypertrophy to compensate those that have been lost.
Creatinine blood value = 1mg% (100% of nephrons are working), 2mg% (50% of nephrons
are working), 4mg% (25% of nephrons are working).

62. Chronic renal failure – alterations of sodium and potassium

Glomerular filtration is decreased so there will an increased retention of water > increase
retention of water > edema. The body responds by decreasing the secretion of aldosterone
and increase that of natriuretic peptides to maintain homeostasis.
Volume depletion due to diarrhoea or vomiting can also occur.
 Potassium is usually excreted in the late part of the nephron, in renal disease, the
reabsorption will be until the end and there will be hyperkalemia. The body maintains
potassium homeostasis in this case by increasing excretion of it through digestive tract.

63. Chronic renal failure – alterations of calcium and phosphate

There will be hyperphosphatemia, and at the same time hypocalcaemia because serum
calcium is inversely regulated in relation to serum phosphate levels.
Hypocalcaemia is due to decrease of 1,25 dihydrocholecalciferol > decreased digestive
absorption > high concentration of PTH
Hyperphosphatemia > combines with calcium > no more response to PTH
Consequences of hypocalcaemia:
- Secondary hyperparathyroidism
- Erythropoietin deficit leading to normocytic normochromic anaemia
- Nausea, vomiting
- Volume hypertension
- Thrombocytopathy

64. Chronic renal failure – endocrine dysfunctions

Drop in serum calcium will stimulate PTH secretion, with a resultant increase in calcium
reabsorption from bone. PTH does the opposite for phosphate by inhibiting renal
reabsorption of it. Exaggerated concentration of PTH increase calcium reabsorption from
bone and lead to osteoporosis. Calcium-phosphate complexes form and are stored in
different places in the body with important disturbances.

65. Heart failure – definition and generalities

A failing heart is unable to pump blood to the peripheral tissue.
Cardiac output = stroke volume x heart rate
Most frequent cause is ischemia.
Cardiac output reduced during heart failure due to smaller force of contraction.
Preload (end diastolic volume that stretches the right and left ventricle) can be normal but
because of reduced contractibility of heart not all blood will be evacuated. Afterload
(pressure in the wall of left ventricle) is lower due to left ventricle dysfunction.
Compliance (the filling of the ventricle during diastole) is also diminished.
In essential hypertension there is increased afterload and get tired easily. In secondary
hypertension, increase in catecholamines > pheochromocytoma > retrograde pressure >
acute pulmonary edema

66. Compensatory mechanisms of the heart failure

A) Frank-Starling law, myocardial fibres are getting longer and longer (max is 2.2 microns).
Their strength will be increased parallel with the length of the fibre.
B) Left ventricular hypertrophy, if fibres are longer, left ventricle will pump with an increase
force of contraction to defeat the resistance, leading in time to hypertrophy.
 C) RAAS, renal hypoperfusion and hypoxia lead to activation of this system. Also causes
water and sodium reabsorption.
D) Excessive catecholamine release from adrenal medulla, they cause vasoconstriction and
increase heart rate
67. Pathogenetic mechanism of heart failure – volume overload
Initially increased compliance but there is a decrease in the force of contraction, due to a
massive dilation of the left ventricle.
Finally the end diastolic volume increases but the end diastolic pressure decreases.
[Increased preload]

68. Pathogenetic mechanism of heart failure – pressure overload

Left ventricle has to work harder and harder and will hypertrophy bringing an increase in
contraction force. This will bring an improper compliance with a decrease in end diastolic
volume and an increase in end diastolic pressure.
This increases oxygen demand. [Increased afterload]

69. Chronic heart failure – decreased contractility

In acute myocardial infarction, a destruction of over 40% of myocardium causes cardiogenic
shock. Less than 40% causes a decreased contractility and overtime leads to chronic heart
failure. End diastolic volume/pressure and end systolic volume are all decreased.
70. Chronic heart failure – compliance
The heart isn’t able to relax properly and accept proper volume of blood from left atrium
during decreased compliance. In the end, increased diastolic end pressure and end diastolic
volume is decreased. Happens during amyloidosis, cardiomyopathy, during temponate,
during pericarditis and mitral regurgitation.

71. Systolic dysfunction

Left ventricle is not able to contract properly and is not able to send a proper volume of
blood into the peripheral tissues. It occurs during aortic stenosis, hypertension, MI,
myocarditis, bacterial or viral infection.

72. Diastolic dysfunction

The compliance of the heart (left ventricle) is affected meaning that not enough blood will
get to the left ventricle during diastole. Occurs during temponate, pericarditis, infiltration of
left ventricular muscle and deficient ATP.

73. Hypertension generalities

Leading risk factor for cardiovascular disorders
More common in young men and blacks
From clinical point of view hypertension is defined as a persistent increased blood pressure
over the norm = greater or equal to 140/90 mmHg
Three factors determine blood pressure: cardiac output, total peripheral resistance (these
two short term blood pressure regulation) and homeostasis between blood and interstitial
fluid (long term regulation of blood pressure)
 Symptoms are: headache, nausea, vomiting, dizziness, tinnitus, fatigue, shortness of breath,
convulsion, anxiety, changes in vision, pale/red skin, and palpitations.
Consequences of hypertension are: thrombotic and haemorrhagic stroke, MI, acute
pulmonary edema, coronary artery disease and is also a major risk factor for atherosclerosis

74. Mechanism of essential hypertension

Unknown mechanism and is classified into optimal (<120), normal (<130), high-normal (130-
139), hypertensive stage 1 (140-159), hypertensive stage 2 (160-179) and hypertensive stage
3 (>180)
Constitutional factors: family history, race, diabetes mellitus, age-related
Life style factors: high sodium intake, excessive calorie intake, physical inactivity, excessive
alcohol consumption.
Asymptomatic disorder but in long term it affects kidneys, heart, eyes and blood vessels

75. Secondary hypertension – renal origin

It is the hypertension cause by reduced renal blood flow leading to activation of RAAS.
Renovascular hypertension can be due to:
- Hypertrophy of renal arteries
- Retroperitoneal fibrosis (Ormond disease), proliferation of fibrous tissue in
retroperitoneum
- Obstruction/compression of renal vessels
- Renal artery stenosis
- Embolism of renal vessels
- Deterioration of renal vessel

Most common source of secondary hypertension is reduction of sodium secretion >

sodium retention > volume hypertension

Diuretics are given as treatment. 60% of cases have normal renin, 30% decreased renin
and 10% increased renin. Liddle syndrome caused by disregulation of some sodium
channel in epithelium of kidney (low renin, metabolic alkalosis due to hypokalemia and
hypoaldosteronism)

76. Secondary hypertension – endocrine origin

A) Disorders of adrenocorticosteroid hormones
- Excess production of aldosterone, sodium reabsorption > volume hypertension
- Deoxycorticosterone (DOC), precursor of aldosterone favouring hepatic synthesis of
angiotensinogen. Also increase sodium reabsorption and potassium excretion.
- Hyperthyroidism, increases heart rate and metabolism + oxygen demand
- Excess levels of glucocorticoid (Cushing disease), high levels of cortisol and 11-beta-
hydroxysteroid dehydrogenase is overwhelmed.
B) Excessive catecholamine release
- Pheochromocytoma, adrenal medulla tumour with excessive catecholamine
excretion
C) Contraceptives, oestrogen increase can lead to hypertension
77. Secondary hypertension – cardiovascular origin
- Coarctation of aorta, narrowing of the aorta, higher pressure in arms than in legs.
RAAS > generalised hypotension
- Salt induced hypertension
- Atrial natriuretic peptide, natriuresis + vasodilation + suppression of RAAS.
Exaggerated production of ANP > calcium channels open > increases contraction >
secondary hypertension
- Excessive coffee intake
- Energy drinks very dangerous can lead to MI or heart arrest
- Metabolic syndrome, insulin resistance, obesity
- Pregnancy

78. Shock – definition and generalities

It is reduced the reduced perfusion of peripheral tissues of different organs regardless of the
initial cause.
Tachycardia begins followed later by bradycardia.
Reduced renal perfusion leads to reduced urinary flow and renal failure
Reduced brain perfusion leads to dizziness, confusion, agitation, syncope
Reduced skin perfusion leads to dry, pale, cold skin
Acidosis and decreased heart rate due to lack of oxygen

79. Hypovolemic shock

Due to reduced blood volume, preload is reduced, normal afterload, vasoconstriction (cold
skin)
A) Post-haemorrhagic
- Most important and well known shock
- External bleeding can be easily seen
- Internal bleeding is tricky especially in upper digestive haemorrhage, broken spleen
B) Traumatic shock
- Both internal and external bleedings (crash syndrome)
- Skeletal muscle destruction (rhabdomyolysis) leading to myoglobin release which
causes renal hypoperfusion and obstruction > necrosis and renal failure. Toxic levels
of calcium.
C) Burn shock
- Loss of plasma
- Very exposed to infection
D) Massive dehydration
- Young children after vomiting or diarrhoea
- Diabetes insipidus
- Removal of obstruction where fluid accumulated
- Decrease of ADH (hypofunction of adrenal gland)
- Mucoviscidose (lack of digestive enzymes)

80. Cardiogenic shock

Preload is normal but heart contractility is reduced of left ventricle.
 There is hypoperfusion of peripheral tissue that decreases backward pressure.
Increase in end diastolic pressure goes to left atrium and will cause pulmonary edema.
Obstructive shock is obstacle in front of left ventricle such as aortic stenosis, mitral stenosis,
atrial myxoma, tamponade, and embolism.

81. Distributive shock

Normal preload and contractility but deficient afterload (vasodilation, vessel elasticity
affected)
A) Anaphylactic shock
- Allergies that trigger mast cell degranulation with release of histamine (powerful
vasodilators)
B) Septic shock
- Bacteria releasing endotoxins and viruses
C) Neurogenic shock
- Exaggerated discharge by autonomic system such as micturition syncope, deglutition
syncope, coughing syncope and effort syncope.

82. Compensatory mechanism of shock

- RAAS activated: compensatory vasoconstriction
- reabsorption of sodium and water ↑
- ↑ catecholamines: ↑HR, vasoconstriction, ↑ activity of ♥