General: Topic 1 - 5 Flashcards
Definition of a disease
Any deviation from, or interruption of, the normal structure or function of any part, organ, or system in the body that is manifested by a characteristic set of symptoms and signs, whose aetiology, pathology, and prognosis may be known or unknown
What is the lasting word for disease?
Mortis
What is the dynamic process of a disease?
Cause —> Incubation —> Onset —> Crisis —> Death / Recovery
Name a “stable” pathological process?
Congenital defects, e.g. cleft palate
How do we classify diseases?
- Classified by symptoms
- Classified by length / course of disease
- Classified according to cause
How are the different “lengths” of a disease classified?
- Foudryant (immediate)
- Apoplectiform (almost immediate)
- Peracute (hours / day)
- Acute (days)
- Subacute (weeks)
- Chronic (months / years)
How are the different causes of a disease classified?
- Genetic (always congenital)
- Congenital (not always genetic)
- Acquired (environmental)
- Monofactorial / polyfactorial
What is homeostasis?
The maintenance of a stable internal environment of an organism.
What is homeostasis made up of?
- Isovolaemia
- Isoosmosis (isotonia)
- Isoionia
- Isohydria
- Isothermia
Which element of homeostasis is the most important one to restore?
Isovolaemia
What is the (basic) result of water loss?
Increased osmolarity of the plasma (hyperosmosis)
What are the two elements of water loss compensation?
Endogenous and exogenous compensation
What happens in the endogenous compensation mechanism during water loss?
- Osmoreceptors sense the increased osmolarity
2. ADH secretion increases —> Water absorption in the kidney tubules increases (ascending Henle loop + distal tubule)
What happens in the exogenous compensation mechanism during water loss?
The thirst centre in the hypothalamus is triggered:
- Sensation of thirst
- Increased water intake
What happens when ADH secretion increases?
Water absorption in the kidney tubules (ascending Henle loop + distal tubule) increases
What happens when ADH secretion decreases?
Increased water loss occurs (excretion) in the kidney tubules
What is ADH?
Antidiuretic hormone / Vasopressin
Where is ADH produced?
In the neurons of the hypothalamus (peptide prohormone) —> Posterior pituitary (released into circulation)
Where is the sensation of thirst produced?
Hypothalamus
What is the osmolar gap?
Measured serum osmolarity - calculated osmolarity
What is the normal value for the osmolar gap?
<10 mosm / kg
What is the JGA?
The juxtaglomerular apparatus
Where is renin produced / released?
The juxtaglomerular apparatus
What is renin transformed into, and where does this transformation take place?
Transformed into Angiotensinogen by the liver
Where is Angiotensin I transformed int o Angiotensin II?
In the pulmonary and renal epithelium
What are the actions of Angiotensin II?
- Triggers Aldosterone secretion from the adrenal gland
- Systemic vasoconstriction
- Glomerular arteriolar vasoconstriction (efferent > afferent)
What is the role of aldosterone?
It causes water AND Na+ retention in the kidney tubules, which leads to an increased plasma volume and an increased osmotic concentration
What happens when the kidney retains water and Na+?
The plasma volume and the osmotic concentration of the plasma increases
Where is Angiotensin II transformed into Angiotensin III?
In the lungs
What does Angiotensin III cause?
Vasoconstriction in the small arteries; which leads to an increased blood pressure
What kind of receptors can you find in the JGA?
Baroreceptors
What do baroreceptors sense?
Blood pressure
What is the basic explanation of the renin-angiotensin system?
The RAS is a hormone system that regulates blood pressure and fluid balance
What does the JGA sense?
Changes in plasma volume and blood pressure
Explain the whole RAS
- JGA senses a decrease in the plasma conc. and BP
- Renin is secreted from JGA
- Renin is transformed to Angiotensin (AT) 1 in the liver
- AT1 is transformed to AT2 in the pulmonary and renal epithelium
- AT2 causes water and Na+ retention in the kidneys, which leads to an increase in plasma volume and osmotic conc.
- AT2 is transformed to AT3 in the lungs, which leads to vasoconstriction of small arteries —> Increase in BP
What are disorders of water balance usually associated with?
- Volume- and osmoregulation (Na+ and albumin, glucose metabolism)
- Kidney function (ADH and aldosterone effect)
Where is aldosterone produced / secreted?
In the Zona glomerulosa of the adrenal cortex (in the adrenal gland)
What are the primary forms of water balance disorders?
Dehydration and hyper-hydration
What are the secondary forms of water balance disorders?
Following isotonic and isoionic changes
What are some causes of Na+ plasma loss?
- Chronic renal failure
2. Addison’s disease (Hypoadrenocorticism)
What is a homeostatic (indirect) cause of dehydration?
Increased Na+ loss
What is a homeostatic (indirect) cause of hyperhydration?
Increased Na+ retention
What are some reasons for increased Na+ retention?
- Acute renal failure
- Salt poisoning
- Hyperaldosteronism
a. Primary: Adrenal hyperfunction (Conn’s syndrome)
b. Secondary: Adrenal hyperfunction + liver failure
What is Oedema?
A fluid accumulation in the interstitial space
What are some intravascular factors that cause Oedema?
- Increase of hydrostatic pressure ( resulting from inc. blood volume)
- Decreased oncotic pressure (caused by hypoalbuminaemia)
What can cause hypoalbuminaemia?
- Liver disease
- Protein losing enteropathy / nephropathy
- Starvation
- Inc. permeability of blood vessels
What are some interstitial factors that cause Oedema?
- Inc. in oncotic and osmotic pressure (outside of the blood vessels)
- Disorders of the lymph flow
What are the types of oedema?
- Oedema stagnationis
- Oedema dysprosium (cell membrane disorders)
- Oedema ex. Hypoproteinaemia
- Oedema lymphangioticum (Change in lymph vessel capacity)
- Oedema hormonal (endocrine disturbances)
Describe the events that follow a blood pressure drop
Atrial stretch receptors —> Hypothalamus —> Vasopressin (ADH) —> Medulla oblongata —> SNS —> Cardiac muscle cells of the atrium —> Atrial natriuretic peptide (ANP)
What is ANP?
Atrial natriuretic peptide is a peptide hormone
How does ANP affect Renin and Aldosterone?
Renin secretion in inhibited, and thereby the production of angiotensin and Aldosterone is inhibited
What does aldosterone do?
Increases the renal retention of Na+ and secretion of K+, thereby reabsorbtion of Na+ and water occurs
What does ANP do?
It acts on the kidneys to increase Na+ and water excretion by:
- Increases GFR
- Increases blood flow through kidney
- Decreases NA+ reabsorption
- Inhibits Renin secretion, and thereby also inhibiting angiotensin and aldosterone production
ANP has the opposite effect of which other hormone?
Aldosterone
Which hormone has the opposite effect of Aldosterone?
Atrial Natriuretic peptide
Describe the events that follow a blood pressure increase
Atrial stretch receptors —> Hypothalamus —> Vasopressin (ADH) —> Medulla oblongata —> SNS —> Chemoreceptors of JGA —> Renin-angiotensin system
Describe the neural / hormonal regulations of hyperosmosis
Hyperosmosis —> Osmoreceptors —> Neurohypophysis —> ADH release
Describe the neural / hormonal regulations of Hypovolaemia
Hypovolaemia —> Baroreceptors (senses volume) —> JGA renin release —> Angiotensin 1, 2, 3 —> Aldosterone release
Describe the neural / hormonal regulations of hypervolaemia
Hypervolaemia —> Atrial Baroreceptors —> ANP —> Na+ and water excretion through the kidney increases (reabsorbtion inhibited)
What is the most prominent cation of the EC space?
Sodium (Na+)
What is the main role of sodium in the extracellular space?
Along with Cl- it maintains isoosmosis (responsible for 90% of the osmolality)
The Na+ concentration of which bodily fluid reflects that of the plasma concentration?
Saliva
What is important for NA+ reabsorption in the kidneys?
Aldosterone
Name all the hormones / peptides that affect Na+ balance
- Aldosterone (Inc. Na+ and water, Dec. K+)
- Angiotensin II
- ANP
- Renin
- Catecholamines
What is another word for dehydration?
Hypovolaemia
What is happens when hypertonic dehydration to occur, and what is the resulting plasma change?
H20 loss
Hyperosmosis
What is happens for hypotonic dehydration to occur, and what is the resulting plasma change?
NaCl loss
Hypoosmosis
What is happens for hypertonic hyper-hydration to occur, and what is the resulting plasma change?
H20 overload
Hypoosmosis
What is happens for hypotonic hyper-hydration to occur, and what is the resulting plasma change?
NaCl overload
Hyperosmosis
What is another word for hyperhydration?
Hypervolaemia
What is an important hormonal feature of Diabetes Insipidus?
ADH deficiency
What are the two“types” for Diabetes insipidus?
- Central
2. Peripheral
What is the cause of “central” Diabetes insipidus?
Damage to the hypothalamus or pituitary gland
E.g. from stroke, tumour, etc.
What is the cause of “peripheral” Diabetes insipidus?
Inability of the nephrons of the kidney to respond normally to ADH
Name some reasons for Isotonic hypovolaemia
- Blood loss
- Vomiting
- Diarrhoea
- Chronic renal failure
What are two compensational processes in the event of Isotonic Hypovolaemia?
- Increased water intake: Polydipsia
2. Decreased urine excretion: Oliguria / Anuria
What is exsiccosis, and what is an important clinical sign?
Exsiccosis = A condition that results from excessive water loss
Clinical sign = Sunken eyes
What is the main cause of hypotonic hypovolaemia, and what is the result?
Loss of water and saline (albumin, glucose, etc.) simultaneously
Result: Decreased EC (hypotonia) with hyponatraemia
What is the compensation process in the case of hypotonic hypovolaemia?
Water transport from the EC to the IC
What is the consequence in the case of hypotonic hypovolaemia?
Decrease in EC volume + Increase in IC volume, resulting in swelling of cells / haemolysis
What is the main cause of hypertonic hypovolaemia, and what is the result?
Decrease in water intake, or a loss of water
Result: Hypernatraemia with a decreased EC + hyperosmosis
What is the compensatory process in the case of hypertonic hypovolaemia?
Water transport form the IC to the EC (not very effective)
What is the consequence of Hypertonic hypovolemia?
EC and IC water contend decrease —> Cell shrinkage
Results is a total / global dehydration (“salt poisoning”)
What are the two main causes of Isotonic hypervolaemia?
- Saline and water intake (or retention) proportional increase
- Could be caused by iatrogen hyperfusion of saline
What are the consequences of Isotonic hypervolaemia?
- Increased hydrostatic pressure + decreased oncotic pressure
- Fluid excretion increases from the blood vessels into the interstitium
- General oedema develops
What is the cause of Hypotonic hypervolaemia?
Water intake / retention increases non-proportionally with saline increase
What are the consequences of hypotonic hypervolaemia?
- Increased EC volume
- Hyponatraemia
- Fluid moves from EC to IC (Inc. in both EC and IC)
- Oedema is rare, but haemolysis / cell swelling always occur
What are the causes of hypertonic hypervolaemia?
- Salt intake increases or salt loss decreases (salt poisoning)
- Could occur when drinking sea water
- Could occur with iatrogen overdose on hyperosmotic saline
What are the consequences of hypertonic hypervolaemia?
- Hypernatraemia (hyperglycaemia, etc.)
- Water transport from IC to EC (cellular exsiccosis)
- Oedema can develop, but this is rare
Which animals are the most sensitive to hypertonic hypervolaemia?
Birds and pigs
Name some reasons for Hyponatraemic hypervolaemia
- Excessive water intake
- Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
- ADH intake
- Rapid infusion of hypovolaemic fluid (iatrogenic)
- Reset osmostat syndrome
Name the two main reasons for Hyponatraemic normovolaemia
- Renal losses
2. Oedematous states
Name the renal causes for Hyponatraemic normovolaemia
Renal losses:
a. Diuretic therapy (thiazide)
b. Osmotic diuresis (glucose, mannitol)
c. Advanced renal failure (decreased GFR)
Name the oedematous reasons for Hyponatraemic normovolaemia
Oedematous states
a. Congestive heart failure
b. Liver disease
c. Nephrotic syndrome
Name the two main reasons for hyponatraemic hypovolaemia
- Extrarenal losses
2. Renal losses
Name the extra-renal causes for hyponatraemic hypovolaemia
Extra-renal losses:
- Gastrointestinal disorders (vomiting diarrhoea)
- Third-space disorders (pancreatitis, peritonitis)
Name the renal reasons for hyponatraemic hypovolaemia
Renal losses:
1. Diuretic therapy (thiazide)
What are the symptoms in case of 5-6% dehydration?
No / subtle loss of skin elasticity
What are the symptoms in case of 6-8% dehydration?
- Decrease in skin elasticity
- Slight decrease in capillary refill time
- Eyes may be slightly sunken
What are the symptoms in case of 10-12% dehydration?
- Extremely dry mucous membranes
- Complete loss of skin turgor
- Eyes are dull and sunken into the orbits
- Possible signs of shock (Rapid (tachycardia) and / or weak pulse, cool extremities, altered consciousness)
What are the symptoms in case of 12-15% dehydration?
- Definite signs of shock (Rapid (tachycardia) and / or weak pulse, cool extremities, altered consciousness)
- Death is imminent if not quickly corrected
What are the steps in the clinical approach to dehydration?
- Estimate the volume of fluid lost
- Estimate the ongoing losses
- Calculate the maintenance requirement
- Add the values from step 1-3 to get the volume to be administered in a 24 hour period
What is the definition of oedema?
Fluid accumulation in the interstitial space (part of EC)
What are the two main causative factors of oedema?
- Intravasal factors
2. Interstitial factors
What are the causative intravasal factors that cause oedema?
- Increased hydrostatic pressure
- Decreased oncotic pressure (drop in albumin)
- Increased permeability of blood vessels
What are the causative interstitial factors that cause oedema?
- Increased oncotic and osmotic pressure outside the blood vessels
- Disorders of the lymph vessels / flow
What are the major cations of the EC fluid?
Na+, K+, Ca2+, Mg2+
What are the major anions of the EC fluid?
Cl1, HCO3-, proteins, and “others”
What are the major ions of the EC fluid?
Na+, K+, Cl-, and HCO3-
What is the anion gap?
The difference in the measured cations and anions in the EC
What causes the anion gap?
Unmeasured anions; Lactate, phosphate, sulphate, other organic anions, and proteins
What is the normal range of the anion gap (and what is the formula to calculate it)?
((Na+) + (K+)) - ((Cl-) + (HCO3-)) = 12-18 mmol / l
What is measuring the anion gap useful for?
Useful to distinguish different forms of acidosis
