Ndjskkdkdndnxnxnxndndytes-Students-2024.ppt

Dndjkdkdnxxokxj

1. Water
Distribution :
1. Total body Water : Healthy 70kg (adult) man contains
approx. -42 L (60% of body weight)
2. Extracellular fluid-14L ,,(20% ,, ,, ,, )
a. Plasma -03L ,, (05% ,, ,, ,, )
b. Interstitial fluid-11L,,(15% ,, ,, ,, )
(Intercellular fluid)
3. Intracellular -28 ,,(40% ,, ,, ,, )
Note : a. women & obese individuals have relatively less
water due to higher content of stored fat (anhydrous form)
b. Pregnant & Children have more T.W. (approx. 70%) 1

2. There can be considerable variation in body
water percentage based on a number of factors
like
age,
health,
water intake,
Weight
sex2
2

3. 3

4. Bloodcontain both
ECF(the fluid in the
plasma) & ICF(the fluid
in the red blood cell)
Capillary:smallest of
blood vessels where
physical exchange
occurs between the
blood and tissue cells
surrounded by
interstitial fluid
4

5. Transcellular fluid :
1. part of ECF formed by transport or secretory
activity of cells.
2. separated from plasma by an aditional epithelial
cell layer along with capillary endothelium
3. rich in mucopolysaccharide / glycoprotein make
the fluid slippery, acting biological lubricant.
4. present in potential spaces of the body.
Examples: 1. cerebrospinal fluid (CSF)
2. synovial fluid
3. peritoneal fluid
4. pleural fluid
5. Intraocular fluid (aqueous humour)
6. gastro intestinal secretions
7. urine
8. sweat
5

6. 6

7. Measurement of body fluid compartment :
Technique: Indicator(dye) or isotope dilution technique
m m
Principle: C = ----or V = ----
v c
m = total amount of indicator injected into the compartment
c = concentration of the indicator in the compartment
v = volume of the compartment
Indicator used :
1. for measurement of TBW -Deuterium/Tritium oxide,
Antipyrine
2. ,, ,, of ECF -Inulin, mannitol, sucrose
Isotope of sodium / chloride
3. ,, ,, of Plasma -Evan’s blue, Radioiodinated
serum albumin
7

8. Calculation of ICF & Interstitial Space :
1. ICF volume = TBW -ECF
2. Interstitial Space volume = ECF -Plasma volume
8

9. Water intake :
Total (approximately) -2500 ml / day
a. drinking water & beverages (exogenous) -1500 ml / day
b. food water ,, -700 ml / day
c. metabolic water (endogenous) -300 ml / day
Water output :
Total (approximately) -2500 ml / day
a. urine -1000 -2000 ml / day
b. skin (insensible loss) -450 ml / day (perspiration)
c. lungs ,, -400 ml / day(Transpiration)
d. faeces -150 ml / day
9

10. Excess water loss
from the skin:
heat,exercise,
burns, severe skin
diseases
Excess water loss
from the GI tract:
vomiting, diarrhea,
intestinal fistula,
nasogastric suction.
Drugs, Chronic
obstructive
pulmonary disease,
Asthma causes
excess insensible
water loss
10

11. Water balance :
1.Positive water balance : intake is more than output
a. growing subject
b. Pregnancy
2.Negative water balance : output is more than intake
a. less intake
b. vomiting , diarrhoea
c. loss of blood
d. diabetes mellitus
e. diabetes insipidus
11

12. Obligatory water intake (Drinking water):
650ml/day
Obligatory water loss is about 1500ml/day.
It consists of:
Insensible water loss-1000ml/day
Obligatory urine volume-500ml/day.
12

13. Functions of water :
1. water is the solvent of life
2. provides the aquous medium for various bio. reactions
3. participates as reactant in several metabolic reactions
4. acts as vehicle for transport of solutes.
5. associated with regulation of body temperature
6. forms urine & clears metabolic waste products
7. maintain ECF (blood) & ICF volume, osmolality and BP.
13

14. Metabolic water
It is the endogenous water produced by oxidation
of carbohydrate, protein & fat at cellular level.
It is regarded as insensible water gain to the body
& in an adult on average diet it is about 300 –400
ml/day.
Metabolic water production for:
Fat = 1ml/g , Protein = 0.8 ml/g , Carbohydrate =
0.6 ml/g
14

15. Insensible water loss : It is the evaporative water
loss beyond the conscious of an individual
through skin and expired air by perspiration (450
ml/d) and transpiration (400ml/d) respectively.
It is about 800 –1000 ml/d or 10 ml/kg/day and
it depends on:
Body surface area & Respiratory rate.
Body temperature & atmospheric temperature.
It is important for thermoregulation of body.
15

16. Water turnover
It is the percentage of ECF volume that an
individual
loses and again make up every day.
Water turnover = Intake or outputx 1000
ECF volume
= 18% ( In adult)
Water turnover in case of infants & children is
about 40-50% of ECF.
Water turnover in an individual depends on:
Dietary habit, Physical activity, Metabolic
state,
Atmospheric temperature
16

17. Regulation of water balance :
Factors :
1. Thirst -↓water ↑blood osm. ↑thirst centre( hypothalam)
↑thirst ↑intake → balance
2. Kidney -↓water ↓urine → balance
-↑water ↑urine → balance
3. Aldosterone-↓water ↓renal blood flow ↑renin-angiotensin
system ↑Aldosterone ↑ Na++ reabsorption
↑water reabsorption → balance & vice versa
4. ADH -↓water ↑ blood osmolality ↑hypothalamus ↑ADH
↑water reabsorption → balance & vice versa
17

18. 5. Renin-Angiotensin system -↓water ↓renal blood flow
↑renin secretion(JGA) ↑Angiotensin II ↑Adrenal cortex
↑Aldosterone secretion ↑Na++ reabsorption
↑water reabsorption → water balance & vice versa
6. ANP -↑water ↑bl.vol. ↑venous return ↑right atrium ↑ANP
↑Na++ excretion ↑urine → balance
7. Hypothalamus -regulates through thirst & ADH mechani.
8. Electrolytes -↓water ↑Na++ conc. in blood
↑water retension → balance & vice versa
9. Temperature & Humidity -↑ temp. ↑perspiration ↑ w. loss.
10. Diet -liquid & semi liquid ↑water, solid diet ↓water
18

19. 19

20. Dehydration :
Def : Dehydration is a condition characterized by water
depletion in the body due to insufficient intake
or loss or both.
Types : 1. due to loss of water alone
2. due to deprivation of water & electrolytes
Causes:
1. diarrhoea, vomiting, sweating, burns, hemorrhage
2. adrenocortical dysfunction (Adison’s disease)
3. kidney diseases (Renal insufficiency)
4. deficiency of ADH (diabetes insipidus)
5. uncontrolled diabetes mellitus etc.
20

21. •There are three main types of dehydration:
hypotonic (primarily a loss ofelectrolytes),
hypertonic (primarily loss of water) and
isotonic (equal loss of water and electrolytes).
•The most commonly seen in humans is
isotonic.
21

22. •Isotonic waterloss occurs when water and
sodium are lost together.
•Causesof isotonic water loss are
-vomiting,
-diarrhea,
-sweating,
-burns
-intrinsic kidney disease,
-hyperglycemia, and
-hypoaldosteronism.
22

23. •Hypertonic dehydration occurs when water
losses exceed sodium losses.
•Serumsodium and osmolality will always be
elevated in hypertonic dehydration.
•Excess pure water loss occurs through the
skin, lungs, and kidneys.
•Etiologies are fever, increased respiration,
and diabetes insipidus.
23

24. •Hypotonic dehydration is mostly caused by
diuretics, which cause more sodium loss
than water loss.
•Hypotonic dehydration is characterized by
low sodium and osmolality.
24

25. 25

26. 26

27. Characteristics Features of dehydration :
1. ↓ECF & ↑electrolyte conc. ↑osmotic pressure(osmolality)
2. withdrawl of water from ICF → shrunken cells & increase
protein breakdown
3. ↑ADH secretion → water retension → ↓urine volume
4. ↑blood urea level
5. electrolyte imbalance
6. ↑ pulse rate, ↓BP
7. shrunken eye balls
8. ↓skin turgor (elasticity)
9. mental confusion
10. coma
Treatment : water & electrolyte replacement by ors or i/v fl.
27

28. •The treatment choice of dehydration is-
-Intake of plenty of water
-The subjects who cannot take orally,
water should be administered intravenously in
an isotonic solution (5% glucose).
-If dehydration is accompanied by loss of
electrolytes
water & electrolyte replacement by ors or i/v
fluid
Oral rehydration therapy (ORT) is commonly
used to treat diarrhoeal disease.
28

29. Oedema
Def :Excess accumulation of fluid(water) in the interstitial
space.
Types : 1. Generalized oedema 2. Localized oedema
Conditions for generalized oedema :
1. cardiac failure
2. nephrotic syndrome (massive proteinuria)
3. acute renal failure (oliguric)
4. chronic renal failure (advanced)
5. hepatic failure (cirrhosis)
29

30. Cond. oedema
6. protein loosing enterpathy & PEM (kwashiorkor)
7. starvation
8. beriberi (thiamine def.)
9. toxaemia of pregnancy (eclampsia)
10. drugs causing Na+ retention :
Corticosteroids, NSAIDS, Antihypertensive :
(calcium channel blockers, vasodilators)
Management principle : 1. restriction of dietary Na+ (salt)
2. ,, ,, water (if necessary)
3. specific treatment of cause
30

31. 31

32. Water intoxication(Overhydration)
Overhydration is caused by excessive retention of
water in the body.
Cause: -Intake of large volume of salt free fluids
-Renal failure
-Overproduction of ADH
-After major trauma or operation
-Lung infections
32

33. Consequence : Retention of water → hyponatremia
→hypoosmolarity of ECF → shifting of water into
the cells → cerebral edema → coma and even
death.
Treatment :
-Stoppage of water intake
-Administration of hypertonic saline
33

34. Electrolytes
Electrolytes are the compounds which readily
dissociate in solution and exists as ions i.e.
positively & negatively charged particles.
Electrolytes are minerals in your blood and other
body fluids that carry an electric charge.
The concentration of electrolytes are expressed as
milliequivalents (mEq/l).
34

35. Functions of electrolytes:
1.General functions
-Maintain body fluid osmolarity& integrity of body
fluid compartments.
-Concern with resting membrane potential &
action potential.
-Concern with neuromuscular irritability,
excitability & tissue function.
35

36. •2. Specific functions
-Calcium helps in coagulation & bone formation.
-Concern with buffering activity ( e.g. bicarbonate
& phosphate ).
-Act as cofactor of enzymes. e.g. Magnesium,
Calcium, Zinc.
36

37. Electrolytes
Major Electrolytes composition of the body
Cations Plasma(ECF) mmols/L ICF(mmols/L)
Na+ 142 10
K+ 05 150
Ca++ 05 02
Mg++ 03 40
Total 155 202
Anions
Cl- 103 02
HCO3- 27 10
HPO4-- 02 140
SO4-- 01 05
Proteins 16 40
Org. acids 06 05
Total 155 202
37

38. •Sodium:135-145 mmol/L ( Average 140 mmo/L)
•Potassium: 3.5-5.0 mmol/L ( Average 4.5 mmol/L )
•Calcium:9-11 mg/dl ( 2.4 mmo/L, 4.8 meq/L
Free: 5 mg/dl
•Chloride: 95-105 mmol/L
•Bicarbonate: 22-28 mmol/L (Average 24 mmol/L)
38

39. ECF ICF
Na+is the principle
cation
K+is the principle cation
This difference in the concentration is essential
for the cell survival whichis maintained by Na
+
-K
+
pump.
Anions Cl
-
& HCO
3
-
predominantly occur in
ECF
Anions HPO
4
-
, proteins
& organic acids are found
in ICF
39

40. Law of electrical neutrality
•In living system every body fluid
compartments is electrically neutral
containing same amount of positive &
negative charge.
•In ECF, total positive charge= Total negative
charge= 155 meq/L
•In ICF, total positive charge= Total negative
charge= 202meq/L
40

41. Law of osmotic Equilibrium
•In a living system a body fluid
compartments are osmotically in
equilibrium having same
osmolarity/osmotic pressure.
•The osmotic pressure of ECF,ICF,ISF &
plasma are identical which is about 280-
300 mosm/L
41

42. •Main determinant of ECF osmolarity is NaCl
& ICF osmolarity is K & its associated anion.
•The retention of water in the ECF is directly
related to the osmotic effect of ions Na
+
& Cl
-

Therefore the amount of Na in the ECF
ultimately determines its volume.
42

43. Osmolarity and Osmolality of body fluids
Def : 1. Osmolarity : The number of moles/mmols per liter
of solution.
2. Osmolality : The number of moles/mmoles per kg of
solvent .
For biological fluids (containing molecules such as
proteins), Osmolality is commonly used, that is about
6% greater than Osmolarity.
Osmolality of Plasma :
It is a measure of the solute particles present in the
fluid medium.
Range of P.Osmolality : 285 -295 mosmoles/kg
43

44. •Measurement of Osmolality :
Na+ and it’s associated anions contrnute approx. 90%
and measured generally by Osmometer.
For practical purpose, Plasma Osmolality can be computed
from the concentrations(mmoles/L) of Na+, K+,Urea and
Glucose
2[Na+] + 2[K+] + [Urea] + [Glucose] = Osmolality
Factor 2 is used for Na+ and K+ and their associate anions
Or shortly, Plasma Osmolality = 2 x P. Na+ (mmoles/L)
Normally, ECF (Na+) Osmolality = ICF (K+) Osmolality.
44

45. •Cont. of P. Osmolality
Movement of water across the biological membranes is
dependent on the Osmotic Pressure differences between
ICF and ECF.
Distribution of constituents in Plasma Osmolality:
1. Na+ + associated anions -135 + 135 = 270 mosmole/kg
2. K+ + ,, -3.5 + 3.5 = 07 ,,
3. Ca++ ,, -1.5 + 1.5 = 03 ,,
4. Mg++ ,, -1.0 + 1.0 = 02 ,,
5. Urea = 05 ,,
6. Glucose = 05 ,,
7. Protein = 01 ,,
Total = 293 ,,
45

46. Plasma osmolarityor osmotic pressure
In normal condition, plasma osmotic pressure (OP) is
about 280 –300 mosm/L.
In normal state, OP of both ICF & ECF is in osmotic
equilibrium.
Cosequenceof osmotic disequilibrium between ICF
& ECF
1.When ECF OP < ICF OP; (e.g. infusion of hypotonic
solution)
•Cellular over hydration due to water entry into
the cells.
•Increased intracellular hydrostatic pressure.
•Impairment of cellular metabolic activities.
•Cerebral edema leading to coma and even death.
46

47. 2. When ECF OP > ICF OP; (e.g. infusion of
hypertonic solution)
•Cellular dehydration due to water loss from the
cells.
•Impairment of cellular metabolic activities.
•K
+
efflux from cells leading to hyperkalemia.
•Cerebral dehydration leading to coma and even
death.
47

48. Consequence of COP disequilibrium across the
capillary endothelium
1. When COP of plasma increase:
Water from extra vascular space enters into
blood vessels to expand blood volume.
2. When COP of plasma decrease:
Water goes out of blood vessel& accumulate in
interstitial space to develop edema.
48

49. Anion gap
Def : Anion gap is defined as the difference
between the total concentration of measured cations
(Na+ & K+) and that of measured anions (HCO3-&
Cl-).
In Plasma ( Law of electrical neutrality)
Na+ + K++ unmeasured = HCO3-+ Cl-+unmeasured
Cations (UC) Anions (UA)
Therefore, with potassium
Anion gap, AG (UA -UC) = ( [N a
+
] + [K
+
] ) -( [HCO3
-
] + [Cl
-
] )
49

50. Without potassium
Because potassium concentrations are very low,
they usually have little effect on the calculated
gap.
Therefore, omission of potassium has become
widely accepted. This leaves the following
equation:
Anion gap (AG) = [Na
+
] -([Cl
−
] + [HCO
−
3])
Normal reference values:
-8 to 16 mEq/L plasma (when not including [K
+
])
-10 to 20 mEq/L plasma when including [K
+
].
50

51. Major unmeasured Cations are :
1. Calcium (Ca
++
)
2. Magnesium (Mg
++
)
3. γ-Globulins
Major unmeasured Anions are:
1. Albumin
2. Phosphate(PO4
--
)
3. Sulphate(SO4
--
)
4. Lactate
5. Other organic Anions
51

52. Anion gap can be classified as:
1. High anion gap
2. Normal anion gap
3. Low anion gap (Rare cases)
Decreased in : 1. Hypoalbuminemia
2. Multiple myeloma
Increased in : 1. Endogenous acid load
a. Diabetic ketoacidosis
b. Lactic acidosis
c. Alcoholic acidosis
d. Renal failure
e. starvation
2. Exogenous acid load
a. Salicylate intoxication
b. Methanol intoxication
c. Ethylene glycol poisoning52

53. Normal Anion gap acidosis :
A. Gastrointestinal HCO3
-
loss:
eg. -i. diarrhoea
ii. a small bowel fistula
iii urinary diversion procedure
B. Renal tubular acidosis (RTA)
C. Ingestion or infusion of inorganic acid:
Therapeutic infusion of or poisoning with NH
4Cl, HCl
D. Carbonic anhydrase inhibitors
53

54. The anion gap is the quantity difference
betweencations(positively charged ions
andanions(negatively charged ions)
inserum,plasma, orurine.
•The plasma anion gap is used mainly in
diagnosing different causes of metabolic acidosis.
If the gap is greater than normal, thenhigh anion
gap metabolic acidosisis diagnosed.
54

55. In patients with a normal anion gap the drop in
HCO
−
3is the primary pathology. The HCO
−
3lost is
replaced by a chloride anion, and thus there is a
normal anion gap.
Lactic acid or ketoacids, is associated with an
increased plasma anion gap because the
fall in HCO3
-
is not matched by an equal increase
in Cl
-
.
55

56. Channels of electrolytes gain & loss :
Gain Loss
1. Food -vegetables & fruits 1. Kidney(urine)
2. Drinks 2. Sweat
3. Drugs-mixures & ORS 3. Faeces
4. I/V Fluids 4. Diarrhoea, vomiting
5. Blood/Plasma transfution 5. Blood loss/Plasma loss
56

57. Regulation of electrolyte balance :
1. Aldosterone -
2. ADH
3. Renin-Angiotensin mechanism
4. ANP
5. Kinins (bradikinin & kallidin) -
Produced in kidney ↑ salt and water excretion,
opposite effect of ADH & Aldosterone
6. Thirst mechanism -hyperosmolarity(↑ Na++)
→↑Thirst centre → ↑intake of water → normal
osmolarity(normal Na++)
57

58. Hormones that regulatetubular reabsorption
Hormone Site of action Effects
Aldosterone Collecting tubule &
duct
↑Nacl,
↑H
2O reabsorption,
↑K
+
seccretion,
↑ H
+
secretion
AngiotensinII Proximal tubule, thick
ascending loop of
Henle/distal tubule,
collecting tubule
↑ NaCl,
↑H2Oreabsorption,
↑ H+ secretion
Antidiuretichormone Distal
tubule/collecting
tubule and duct
↑H
2Oreabsorption
Atrialnatriuretic
peptide
Distal
tubule/collecting
tubule and duct
↓ NaClreabsorption
Parathyroid hormone Proximal tubule, thick
ascending loop of
Henle/distal tubule
↓ PO4 − reabsorption,
↑ Ca++ reabsorption
58

59. Sodium
1. Chief Cation of ECF
2. Distribution : Bones -50% , ECF -40%, Soft tissues -10%
Sources :
1. Common salt (NaCl) for cooking -main source
2. Foods & drinks
Absorption: Readily absorbed in GIT.
Dietary requirement : 5-10 gm as NaCl.
Plasma concentration : 135 –145 mEq / L
( maintained by kidney & regulated by mainly Aldosterone)
Excretion: 1. major rout -Kidney ( 01%),through urine
99% reabsorbed (aldosterone dependent)
2. Sweating
3. vomiting & diarrhoea ↑ loss 59

60. Functions:
1. Maintenance of osmotic pressure, blood volume, BP
2. Maintenance of acid –base balance(with Cl-& HCo3-)
3. Normal muscle irritability & cell permeability
4. Absorption of glucose, galactose, amino acids
5. Initiation & maintenance of heart beat
60

61. Disease states :
1. Hyponatremia :
Causes: 1. Addison’s disease ( hypoadrenalism)
2. Severe vomiting
3. ,, diarrhea
4. ,, burns
5. Intestinal obstruction
6. Nephrosis
Effects:
-Cerebral edema -↓Blood volume
-Nausea -↓BP
-Headache -Circulatory failure
-Delirium
-Muscle weakness,
spasm, cramps
-Seizures
-Coma 61

62. Hyponatraemia is defined as serum Na<135meq/L. It
is a common electrolyte abnormality.
62
•Hypernatraemiais defined when the serum Na is
>145 mmol/L.

63. Hypernatremia :
Causes: 1. Diseases of kidney
(AGN -acute glomerulo nephritis)
2. Cushing’s syndrome(hyperadrenalism)
3. Heart failure (↓ GFR→↑ Na)
4. ↑ administration of Cortisone, ACTH,
Sex hormone
5. Diabetes Insipidus
6. Excess I/V saline administration (rapid)
7. Oral contraceptive pill (↑ Estrogen)
63

64. Effects:
-ECF expansion (hypervolumia)
-Hypertension
-Oedema → pulmonary oedema → respiratory distress
-Cardiovascular embarrassment.
-Cerebral dehydration
-Thirst
-Confusion
-Muscle spasm
-Weakness
-Seizures
-Coma
-Death
64

65. Regulation of sodium balance ( Volume regulation or Regulation of ECF volume)
•Following reduced intake of NaCL
Decreased NaCL intake
↓
Hypovolemia
↓
SNS stimulation ← Inhibition of BR → ANP decreased
↓
RAAS activated
↓
Increased renin
↓
Increased angiotensin II
↓
Increased aldosterone
↓
Salt & water retention → Normal ECF volume
65

66. Regulation of sodium balance ( Volume regulation or Regulation of ECF
volume)
•Following excess intake of NaCL
Increased NaCL intake
↓
Hypervolemia
↓
SNS inhibited Stimulation of BR →ANP increased
↓
RAAS inhibited
↓
Decreased renin
↓
Decreased angiotensin II
↓
Decreased aldosteron
↓
Salt & water excretion → Normal ECF volume
66

67. Disturbance of sodium homeostasis typically
present with-hypovolaemiaor hypervolaemia.
Sodium loss or gain is always accompanied by
water loss or gain
Disturbance of water homeostasis typically
present with-hyponatraemiaor hypernatraemia.
Regulation of sodium balance is equivalent to
volume regulation or regulation of ECF volume
67

68. Water loss will result in decreased volume of both
ECF & ICF. Water gain will result in increased
volume of both ECF & ICF.
Loss of ICF causes cellular dysfunction
(Lethargy, coma, confusion)
Loss of ECF causes dehydration
Loss of blood causes circulatory collapse, renal
shutdown & shock.
68

69. Potassium
1. Chief Cation in ICF(98%) mostly in sk. muscle
2. Important in the ECF(2%) for specific function
Sources :
1. Banana, Green Coconut water, orange, lemon,
grape, pineapple (rich)
2. Other foods & drinks
Absorption: Readily absorbed in GIT (90%).
Daily intake : 50 -100 mmol / day through diet.
Daily output : 50 -100 mmol / day (urine-90 %, sweat,
feces)
69

70. Plasma concentration : 3.4 –5.0 mEq / L
maintained by
1. kidney & regulated by mainly
Aldosterone
2. Transmembrane K+ flux.
Excretion: 1. major route -Kidney ( 01%),through
urine
2. Sweating
3. vomiting & diarrhea ↑ loss
70

71. Functions :
1. Maintenance of ICF osmolarity& cell Volume,
2. Regulation of acid –base balance & water balance
in the cell (maintenance of int. environment)
3. Concern with Resting membrane potential(RMP),
Action potential, transmission of nerve impulses
& tissue excitability.
4. Necessary for protein biosyntrhesisby ribosomes
5. ECF K+ influences cardiac muscle activity.
71

72. Disease states :
1. Hypokalemia:
Hypokalaemiais a common electrolyte disturbance and
is defined as when serum K+ falls below
3.5 mmol/L.
Causes :1. Cushing’s syndrome( hyperadrenalism)
2. Prolonged cortisone therapy,
Hyper aldosteronism
3. Diabetic coma with Insulin therapy
4. Severe vomiting
5. ,, diarrhea
6. Malnutrition
7. Prolonged use of diuretics, Digitalis
8. Nephrosis
9. Metabolic alkalosis.
72

73. Causes of hypokalemia
Reduced intake Dietary deficiency
Potassium-free intravenous fluids
Redistribution into
cells
Alkalosis ,Insulin
Catecholamines,β adrenergic agonists
Hypokalaemicperiodic paralysis
Increased urinary
excretion
Conn syndrome
Cushing’s syndrome
Glucocorticoidexcess
Loop diuretics
Renal tubular acidosis
Increased
gastrointestinal loss
Vomiting
Nasogastricaspiration
Diarrhoea
Bowel obstruction/fistula
73

74. Effects: 1. Muscle cramps, weakness, fatigue
2. Paresis, paralysis, paralytic ileus
3. Tachycardia, cardiomegaly and cardiac arrest
4. ECG change (flattened waves with inverted
“T” wave, ST depression, appearance of U wave
5. Respiratory muscle paralysis
6. Hypokalemic nephropathy.
74

75. 2. Hyperklemia:
Hyperkalaemiais a common electrolyte
disorder, which is denedas when serum K+ is >5
mmol/L.
Causes : 1. Renal failure
2. Addison’s disease ( hypoadrenalism)
3. severe dehydration
4. Shock
5. Diabetic coma
6. Excess I/V saline administration (K+
containing)
7. Hemolysis, Masssiveinjury, severe burn
75

76. Causes of hyperkalaemia
Artefactual Haemolysis during venepuncture
Haemolysis in vitro
Thrombocytosis/leucocytosis
Increased intakeDietary potassium
Potassium-containing intravenous fluids
Redistribution
from cells
Acidosis
Insulin deficiency
Severe hyperglycaemia
Severe haemolysis
Reduced urinary
excretion
Acute kidney injury
Chronic kidney disease
Addison’s disease
Diabetic nephropathy 76

77. Effects :1. Depression of CNS, mental confusion,
numbness
2. Brady cardia, ↓ heart sounds, cardiac arrest in
asystole.
3. ECG changes-elevated ‘T’ wave, loss of P
wave, widened QRS complex
4. Weakness.
77

78. Regulation of potassium balance (Regulation of
potassium homeostasis)
a) Short term regulation (internal potassium
balance)-Done by trans membrane potassium
flux.
b) Long term regulation (external potassium
balance)-Done by renal potassium excretion or
retention and its regulation
78

79. •Short term regulation:
It is done by insulin, aldosterone and
catecholamines.
Hyperkalemia
-Stimulate the release of insulin, aldosterone and
catecholamines.
-All this hormones quickly cause K
+
influx into the
cells
-keep the serum K
+
within tolerable range.
-Allow optimal cardiovascular & neuromuscular
function
79

80. Hypokalemia
•Inhibit the release of insulin, aldosterone and
catecholamines.
•As a result K
+
influx into the cells is inhibited to
allow quick K
+
efflux from the cells.
•This keeps the serum K
+
within tolerable range.
•Allow optimal cardiovascular & neuromuscular
function
80

81. •Long term regulation: Role of kidney
It is done by aldosterone by regulating renal
K
+
excretion/retention.
Renal response starts late and takes time to
be completed.
Hyperkalemia directly stimulate aldosterone
secretion from adrenal cortex to increase
renal K
+
excretion.
81

82. In hypokalemia there is reduction of renal K
+
excretion due to suppression of aldosterone
secretion.
This gradually brings the serum K
+
conc. to
normal.
Transmembrane K
+
flux
In case of potassium overload, potassium
immediately moves into the cell (K
+
influx).
In case of potassium deficit, potassium
immediately comes out of cell (K
+
eflux).
82

83. Factors That Shift K+ Into Cells
(Decrease Extracellular [K+ ])
Factors That Shift K+ Out of Cells
(Increase Extracellular [K+ ])
Insulin Insulin deficiency (diabetes
mellitus)
Aldosterone Aldosteronedeficiency
(Addison’s disease)
β-adrenergic stimulation
especially epinephrine
β-adrenergic blockade such as
propranolol
Alkalosis Acidosis
Cell lysis, Increased extracellular
fluid osmolarity
Strenuous exercise
83

84. 84

85. Calcium
1. Most abundant mineral
2. Total content in adult about 1-1.5 kg
3. Bones & Teeth -99%
4. ECF -0.1%
5. Intracellular fluid and cell organelles –1.0%
Daily requirement :
1. Adult men & women -800 mg / day
2. Preg., Lact., Post menopause -1500 mg / day
3. Children -800 -1200 mg / day
4. infants -300 -500 mg / day
85

86. Sources:
1. Best sources : milk & milk products, fish, meat, egg
2. Other sources : vegetables
Absorption :
1. Calcitriol induces synthesis of ca binding protein
& promotes ca absorption
2. parathormone enhances ca absorption by ↑ synthesis of
calcitriol
3. Lactose, amino acids arginine & lysine ↑ absorption
4. Phytates, oxalates, high phosphates, FFA, alk.pH,
↑ dietary fiber ↓ ca absorption
Plasma concentration :
9 -11 mg / dl (2.4 mmol/L, 4.8 meq/L)
86

87. Forms in plasma:
1. Ionized or diffusible , most active form ( 50%):
4 -6 mg / dl
2. Protein bound form (40%) (non diffusible):
4 -5 mg / dl
3. Salt form (non diffusible) (10%) : < 1 mg / dl
Factors regulating Plasma Ca :
1. Calcitriol increases blood Ca
2. PTH (Parathormone) increases blood Ca
3. Thyrocalcitonin decreases blood Ca
87

88. Functions :
1. Formation of bones & teeth
2. Blood coagulation (Ca++)
3. Regulation of excitability of neurons
4. Generation of nerve impulses & contraction of muscles
5. Regulation of membrane permeability
6. Maintain integrety of intracellular material
7. Acts as cofactors of several enzymes
8. Acts as 2nd messenger of Hormone action
9. Release of certain hormone (Ca++)(insulin, PTH,calcitonin)
10.Regulates endocytosis, exocytosis etc
11. Acts on heart myocardium & prolongs systole
88

89. Disease states :
1. Hypocalcemia :
Causes : 1. Hypoparathyroidism
2. Alkalosis
3. Hyporpoteinemia
4. Chronic renal failure
5. Acute pancreatitis
6. Vit. D (calcitriol) deficiency
7. Hypomagnesaemia
8. Pseudohypoparathyroidism
Effects : 1. Tetany, 2. Rickets, 3. Osteoporosis
89

90. Tetanyin alkalosis: Tetanyis a clinical
manifestations of neuromuscular hyper excitability
that occurs following hypocalcaemia.
Presentation: Carpopedalspasm,
Laryngeal stridor,
convulsion.
90

91. 2. Hypercalcemia :
Causes: 1. Hyperparathyroidism
2. Thyrotoxicosis
3. Vit. D intoxication
4. Pagets disease
5. Sarcoidosis
6. Malignancy ( Lung,breast,,renal, thyroid)
7. HIV virus
8. Glucocorticoid deficiency
Effects: 1. anorexia, nausea, dyspepsia and peptic
ulceration
2. lethargy, drowsiness Constipation, depression,
impaired cognition.
3. bone pain, abdominal discomfort, kidney or
biliary stone
91

92. Regulation of calcium balance/plasma calcium
pool/plasma calcium concentration
a. First line defence
It is done by calcium buffer activity of the
labile calcium pool.
b. Second line defence:
Hormonal regulation
It is done by three hormone;
Calcitriol : Increase blood calcium level.
PTH (Parathormone): Increase blood
calcium level.
Calcitonin: Decrease blood calcium level.
92

93. Hormonal regulation
93

94. Calcium binding capacity of albumin
•Calcium binds with anionic (conjugate base)
form of albumin
•In acidosis anionic form of albumin ( Alb
-
)
decrease as a consequence of the buffering
of proton.
•So there is less binding of calcium with
albumin.
•As a result free calcium increases leading to
hypercalcemia.
Alb
-
+ H
+
HAlb
94

95. •In alkalosis anionic form of albumin (Alb
-
)
increases as a consequence of the buffering
of base by acidic albumin with release of
proton & simultaneous formation of anionic
form of albumin .
•So there is more binding of calcium with
albumin.
•As a result free calcium decrease leading to
hypocalcemia.
HAlb Alb
-
+ H
+
95

96. Hypovolemia
•Hypovolaemia is defined as a reduction in
circulating blood volume. Hypovolemia, also
known asvolume depletionorvolume contraction
•Causes of hypovolaemia:
Inadequate sodium intake-
Environmental deprivation, Inadequate
therapeutic replacement
Gastrointestinal sodium loss-
Vomiting, Diarrhea, Nasogastric suction,
External fistula
Skin sodium loss-
Excessive sweating, burns
96

97. Internal sequestration-
Bowel obstruction, peritonitis, pancreatitis,
crush injury
Renal Sodium loss-
Diuretic therapy, Mineralocorticoid deficiency
Reduced blood volume-
Acute blood loss
Management:
Treat the cause where possible, to stop ongoing
salt and volume losses
Replace the salt & water deficit-
usually by intravenous fluid replacement when
depletion is severe.
97

98. Hypervolaemia
Hypervolaemia is the result of sodium and water
excess and is rare in patients with normal cardiac
and renal function.
Causes of hypervolaemia:
Impaired renal function
Primary renal disease
Primary hyperaldosteronism
Conn syndrome
98

99. Secondary hyperaldosteronism
Congestive cardiac failure,
Cirrhotic liver disease,
Nephrotic syndrome
Protein-losing enteropathy,
Malnutrition,
Idiopathic/cyclical oedema,
Renal artery stenosis
Management:
-specific treatment of the underlying cause
-restriction of dietary sodium
-fluid restriction
99

100. Clinical features of hypovolaemiaand hypervolaemia
Hypovolaemia Hypervolaemia
Symptoms
Thirst
Dizziness on standing
Weakness
Ankle swelling
Abdominal swelling
Breathlessness
Signs
Postural hypotension
Tachycardia
Dry mouth
Reduced skin turgor
Reduced urine output
Weight loss
Delirium
stupor
Peripheral oedema
Pulmonary crepitations
Pleural effusion
Ascites
Weight gain
Hypertension(sometimes)
100

101. Hypovolemichormones (Released in hypovolemia):
-ADH
-Catecholamines
-Renin
-Aldosterone
Hypervolemichormones (Released in
hypervolemia):ANP (Atrialnatriureticpeptide)
ADH/Vasopressin
ADH SYNTHESIS IN SUPRAOPTIC AND
PARAVENTRICULAR NUCLEI OF THE HYPOTHALAMUS
AND ADH RELEASE FROM THE POSTERIOR PITUITARY
101

102. Increase ADH Decrease ADH
↑ Plasma osmolarity ↓ Plasma osmolarity
↓ Blood volume ↑ Blood volume
↓ Blood pressure ↑ Blood pressure
Nausea
Hypoxia
Higher concentrations of ADH have a potent effect
of constricting the arterioles throughout the body
and therefore increasing the arterial pressure. For
this reason, ADH has another name, vasopressin.
102

103. Aldosterone
-Aldosterone, secreted by the zona glomerulosa
cells of the adrenal cortex.
-Is an important regulator of sodium reabsorption
and secretion of potassium and hydrogen ions by
the renal tubules.
-A major renal tubular site of aldosterone action is
on the principal cells of the cortical collecting
tubule.
103

104. The mechanism by which aldosterone increases
sodium reabsorption and potassium secretion is
by stimulating the sodium potassium ATPase
pump on the basolateral side of the cortical
collecting tubule membrane.
-Aldosterone also increases the sodium
permeability of the luminal side of the membrane.
104

105. The most important stimuli for aldosterone are :
(1) increased extracellular potassium
concentration and
(2) increased angiotensin II levels, which typically
occur in conditions associated with sodium and
volume depletion or low blood pressure.
105