Irfan Mir Physiology Usmle Step 1

KICK THE BOARDS
USMLE STEP 1
Physi ology

Pr epar ed by
Dr . Ir f an Mir

KI CK THE BOARDS USM LE STEP 1 Prepared by Dr. I RFAN M I R M D.
1

C ELL PHISIO LO G Y
* Cell mem composed of phospholipids bilayer which contain glycerol back bone.
* Glycerol back bone composed of head (hydrophilic) and two fatty acid tails (hydrophobic). Tails face each other.
* Lipid soluble substance cross cell mem whereas water soluble pass through channel, pores and carriers.
* Inte g ra l p rote in span the entire mem (eg. Ion channel) whereas, peripheral protein located either inter or extra
cellular side.
* Tig ht Junc tion ( zona oc c lud e s) ------- are attachment b/ w cells serve intracellular pathway for solute. It may be tight
(Impermeable) as in renal distal tubules or leaky (permeable) as in renal proximal tubule or gall bladder.
* G a p junc tion -- is attachment b/ w cells which permit IC communication eg. In myocardial cells.
* Simp le d iffusion -- is the transport which is not carrier mediated. It occur down an electrochemical gradient does
not require energy passive.
Diffusion can be measured by J = - PA (C1 - C2) (J= flow, P= permeability, A= area, C= conc entra tion)
* C a rrie r me d ia te d tra nsp ort shows ste re osp e c ific ity, sa tura tion a nd c omp e tition.
Stereospecificty means D-glucose (natural isomer) can transported where as L-glucose (L-isomer) can not.
Saturation means transport | as the concentration | until carriers are saturated called Tm (transport maximum)
Competition means structurally related solute compete for transport site.
eg. (Galac tose is competitive inhibitor of glucose in small Intestine).
* Fa c ilita te d d iffusion -- occur down an electrochemical gradient, does not require energy is passive. It is carrier
Mediated and more rapid than simple diffusion.
* Prima ry Ac tive tra nsp ort -- occur against the electrochemical gradient (up hill). It utilize metabolic energy (from
terminal bond of ATP) is active. It is also carrier mediated ( exhibit stereospecificity, sa tura tion and competition) .
Eg. Na+ - K+ ATPase (usual st oichiomet ry is 3Na / 2K) ,Ca++ ATPase in sarc oplasmic reticulum, K+ - H+ ATPase in parietal cells.
* Se c ond a ry Ac tive tra nsp ort -- in which transport of two or more solute is coupled. One of the solute is transported
down hill (usually Na+) which provide energy for uphill transport of other solute. Metabolic energy provided
indirectly from Na gradient. Thus the inhibition of Na+ - K+ ATPase results into inhibition of Secondary transport.
Eg. Na+ - glucose Cotransport in renal proximal tubule, Ca++ - Na+ exchange, Na+ - H+ exchange. Poisoning the
Na+ - K+ pump eventually results into inhibition of Ca++ - Na+ exchange due Na+ imbalance across cell mem.
* Cotra nsp ort or symp ort is transport of solute in the same direction whereas, C ounte r tra nsp ort or a ntip ort or
e xc ha ng e is the transport of two solute in opposite direction to each other.
* O smola rity is the conc (C) of osmotically active particle in a solution. Osmolarity = g C (g is no of p artic le in the solu.
* Solution with high osmolarity is hyperosmotic, low osmolarity is hypoosmotic, and same osmolarity is isosmotic.
* O smotic Pre ssure (van t Hoff s Law) depends on the conc of osmotic particles. | in solute particle results in |
osmotic P. It can be measured by t = g RT C (Where R is gas constant 0.082L - atom/ mol - K. and Tis
absolute temp K).
* Re fle c tion c oe ffic ie nt is the no b/ w zero & one. It explains the ease with which solutes permeate the mem. If
Reflection coefficient is 1 the solute is impermeable & when it is zero solute is permeable. eg. Reflection coefficient
of albumin (big solute) is 1 where as urea (small solute) is zero.
* Ion c ha nne ls are open or closed by gates.
It may be volta ge g a te d channel which open or closed by change in mem potential. Eg Na channel in nerve
action potential. It may be Lig a nd ( c he mic a l) g a te d channel which open or closed by hormones, second
messenger, neurotransmitters.
* Diffusion p ote ntia l is the potential difference generated across a mem because of conc difference of an ion.
* Eq uilib rium p ote ntia l is the diffusion potential which exactly balance (opposes) the tendency for diffusion caused by
conc difference. There is no more net movement because electrical driving forces on ion are equal and opposite..
* Ne rnst e q ua tion is used to calculate equilibrium potentials. E = -2.3 RT log10 [Ci]
zF [Ce]
E Na+ is + 65mV
E Ca++ is + 120Mv
E K+ is - 85mV
E Cl- is - 90mV
* Re sting me m Pote ntia l is the measured potential difference in mV (millivolts), it is established by diffusion potential.
The resting mem potential of nerve is -70 mV. At rest nerve mem is far more permeable to K+ than to Na+ at rest.
* Thre shold is the mem potential at which occurrence of action potential is inevitable. Inward current depolarize the
mem to Threshold.
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* Upstroke of action potential is depolarization cause rapid opening of the activation gates of Na+ channel. Na
enters into the cell.
* De pola riza tion also open K+ gates and closes the Na+ channel gates but at slower rate. This combined effect make
K+ conductance higher than Na+ conductance in last quarter of depolarization which make mem potential to
Repolarize.
* Re pola riza tion is caused by outward K+ current.
* O ve r shoot is the portion of action potential when mem potential is positive whereas Und e r shoot ( hyp e rp ola riza tion)
makes the mem potential more negative (c lose to K+ equilibrium potential).
* Ab solute ly Re fra c tory p e riod is the period during which another action potential cannot be elicited no matter how
large the stimulus is.
* Re la tive re fra c tory pe riod begins at the end of absolute refractory period and continuous till mem potential return
to its resting potential. Stronger than usual current can elicit the action potential.
* | Fiber size and myelination can | the conduction velocity of action potential. Remember myelinated nerve exhibit
saltatory conduction because action potential can be generated only at the Node of Ranvier.
* End Pla te p ote ntia l (EPP) in the postsynaptic mem is not an action potential but a depolarization of specialized
muscle end plate. Once the end plate region is depolarized local current cause depolarization and action
potential in the adjacent muscle.
* Excitatory postsynaptical potential (EPSP) bring the cell closer to fire action potential where as Inhibitory
Postsynaptical potential (IPSP) hyperpolarize the postsynaptical cell by opening Cl- channels..
* Thick filament contain myosin present at A band. vs. Thin filament contain actin, tropomyosin & troponin present
at I band.
* Myosin head bind ATP and actin and are involved in cross bridging formation.
* Ttubule are present at the junction of A band and I band. It carry depolarization to the interior of the cell.
* Ske le ta l musc le c ontra c tion -- sarcoplasmic reticulum (SR) are internal tubular structure site of Ca++ storage and
release. Ca bound loosely to calsequestrin with in SR & it release upon depolarization bring by Ttubules. Released
Ca+ bind to troponin C on the thin filament causing conformational change in Troponin (which is tropomyosin
moving out of way so that cross bridge cycle can begin). Actin myosin binds and filament slide over each other and
ATP is hydrolysed.
* Le ngth Te nsion re la tionship :-
1. Pa ssive te nsion -- is tension developed by stretching to Fixed length (preload).
2. Tota l Te nsion -- is tension developed when the muscle is stimulated to contract at different length.
3. Ac tive Te nsion -- is the difference b/ w total tension and passive tension.
* Smooth musc le c ontra c tion -- smooth muscle has thick & thin filament & are not arranged in sarcomere. (vs. stria ted m)
There is no troponin instead Ca++ regulate myosin on thick filament Ca++ enter in the cell across cell mem it may
cause release of additional Ca++ from SR via Ca++ - gated channels. Hormones and neurotransmitters also release
Ca++ from SR through IP3 gated Ca++ channels. IC Ca++ |. Ca++ bind to Calmodulin and Ca++ - calmodulin
complex bind to and activate myosin light chain kinase which further phosphorylate myosin and allow it bind with
actin. Contraction follow.
* Dephosphorylation of myosin cause relaxation where as in striated muscle Ca++ uptake cause relaxation.
Remember in heart and striated muscle Ca binds with troponin and in smooth muscle Ca binds with calmodulin.

Figs:

3

ENO DC RO NO LO G Y
* * SEC O ND M ESSENGER SYSTEM :-
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
C YC LIC AM P I P3 C a ++ STERO I DS TYRO SI NE KI NASE C YC LIC G M P
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
CRH GnRH Minera lcorticoids Insulin ANF
ACTH TRH Glucocorticoids IGF EDRF (NO)
TSH GHRH Estrogen
PTH ADH ( V1 ) Progesterone
ADH ( V2 ) Oxitocin Testosterone
|1, |2, o2 o1 Vit D
FSH, LH Angiotensin II T3, T4
HCG CCK
M2 M1 , M3
MSH GABA
Calcitonin
Gluca gon
Secretin
Dopamine
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* TSH, FSH, LH, HC G are the member of same glycoprotein bears o sub unit (identical) & | sub unit (unique for hormone).
* ACTH, M SH, | Lip otrop hin, | End orp hin, all derived from POM C .
* o MSH, and | MSH Rudimentary in adult.
* G HRH G H ( a c idop hillic sta in) .
Functions :- * + Glucose uptake ( Diabetogenic )
* | lipolysis
* | Protein Synthesis ( | LBM )
* | Production of IGF (insulin like growth factor)
* Soma tosta tins and Soma tome d ins have imp negative feed back function.
* Somatostatin block GHRH effect on AP. vs.
Somatomedins cause +ve feedback on the release somatostatin from HT
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* PL ( a c id op hilic to c hromop hob ic sta in) . PL se c re tion | b y TRH and inhib it b y Dop a mine .
Func tion:-* Lactogenesis
* Breast development
* Inhibit Ovulation ( via + Syn of GnRH ) * inhibit spermatogenesis (via + GnRH)
Pa tholog y :- * Failure to lactate
* Failure to ovulate
* Galactorrhea (hypothyroidism can cause increase in TRH with resultant gala c torrhea)
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* ADH originate in supraoptic nuclei of hypothalamus ( Post lobe ). Act on receptors V1 ( vasoconstriction ) and
V2 ( | distal tubule and collecting duct permeability)
* O xitoc in originate in paraventricular nuclei of hypothalamus ( post lobe ). Major stimulus for secretion is Suckling,
sight and sound of infant.
* Ne urop hysin is CNScarrier protein for both hormone (ADH, Oxitocin).

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* C a use s of | or + se c re tion o f ADH :: | Se c re tion o f ADH vs. + se c re tion of ADH
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
* | se rum osmola rity * + se rum osm o la rity
* V o l c ontra c tion * Etha nol
* Pa in, Na use a ( strong ) * o Ag onist
* Hy p og lyc e mia * ANP
* Ne c otinic op ia te
* Antine op la stic d rug
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
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* Func tion of Oxitoc in : Myoepithelial contraction of mammary gland, Milk ejection, Contraction of uterus, Dilatation
of Cervix and Orgasm. ( it can be used to induce labour ).
* TRH TSH T3, T4 ( stored in lumen). ( Ba sop hilic a nd c hromop hob ic sta in)
* Iodide pump ( I - ) present in thyroid follicular epithelial cell.
* Iodide pump Inhibit by Thiocyanate and Perchlorate ion.
* T3, T4 syn can be inhibited by | dosis of Iodine ( I 2 ) this is called Wolf Charkoff Effect.
* T3 is 4 times more potent than T4.
* Thre e sta ge s of TH syn :- 1. O xid a tion :- 2 I - ( Iodide ) I2 ( iodine ) --------- ( Propylthiouracil inhibit oxidation).
2. O rg a nific a tion :- I2 + Tyrosine of Thymoglobulin MIT + DIT
3. Coup ling re a c tion :- MIT + DIT Triidothyroxine T3 ( active form )
DIT + DIT Thyroxine T4
* Befor release Iodinated thyroglobulin first must be taken back into the follicular cell from lumen for digestion of
thymoglobulin by lysosoma l e nz to release T3 T4. ( left over MITand DITare digested by thyroid de iod ina se ).
* T3 T4 circulate by Thyroid Bind ing G lob ulin.
* Conversion of T4 into T3 ( a c tive form) and Re ve rse T3 ( ina c tive form) take place in target tissue by enz Iod ina se .
* Enz 1,5 monod e iod ina se cause break down of T3 and Reverse T3, its deficiency results into | T3 and Reverse T3.
* Func tion of thyroid hormone :-
1. Growth, Bone formation, and maturation.
2. CNS-- Prenatal CNSmaturation
In Adults ---- Hyp e rthyroid ism ( Grave s dis, Plummers $ ) Hyperexcitability, Irritation. Palpitation etc.
Hyp othyroid ism ( Myxedema, Cretinism, Hashimoto thyroiditis, De Quervian thyroiditis, Reidal
thyroiditis ) + mental capacity, impaired memory, slow speech,
listlessness, Somnolence, etc.
3. Autonomic nervous sys :- | Adrenergic Stimulation.
4. BMR :- | O2 consumption and BMR except in Spleen, Gonad and Brain (results into | body temp).
| Syn of Na+ K+ ATPase (results into | O2 consumption)
| HR, | Ventilation (ensure more O2 delivery to tissue)
5. Metabolic effect are over all catabolic .
* Grave dis in which IgG ( thyroid stimulating imunoglobin) | T3, T4

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* PTH is secreted by C hie f c e lls and regulate serum Ca++.
* 1,25 Dihyd roc hole c a lc ife rol is active form of Vitamin D, produce by 1o hyd oxyla se in kidney to Provide C a ++ &
Phosp ha te for normal bone mineralization.
* C a lc itonin Syn and secreted by Pa ra follic ula r c e ll ( C.c e lls ) of thyroid. Its major action is to inhib it b one Re sorption.

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PTH VIT D C ALC ITO NI N
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Stimulus for se c re tion:- + Serum Ca++ + Serum Ca++ * | Serum Ca ++
Mild + in serum Mg + Serum Phospha t Severe + serum Mg inhibit secretion. | PTH

Ac tion on Bone :- | Resorp tion | Resorption * + Reabsorption

Ac tion on Kid ne y :- | Ca++ Reabsorption | Ca++ Reabsorption
+ Ph Reabsorption | Ph Reabsorption

Ac tion on Inte stine :- | Ca++ Absorp tion (via Vit D) | Ca++ Absorp tion (via vit D Ca++ binding Protein)

O ve ra ll e ffe c t :- Serum Ca++ | Serum Ca++ | * Serum Ca++ +
Serum Ph + Serum Ph |
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* Resorption of organic matrix of the bone is reflects in | Hyd roxyp roline Exc re tion.
* PTH | Ca++ reabsorption at distal tubule where as in proximal tubule PTH | inhibit Ph reabsorption with resultant
excretion of nephrogenous cyclic AMP.
* PTH | Vit D production ( indirectly ) by stimulating 1 o Hyd roxyla se .
* Vit D mineralize new bone by | Ca++ and Ph in serum.
* Hyp op a ra thyroid ism Tetany ( + Ca++, | Ph ).
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* Hyp e rp a ra thyroid ism |Ca++,+ serum Ph,| phosphaturia,| Urinary cAMP, | Bone resorption ( with resultant | in
calcitonin & Vit D).
* Pse ud ohyp op a ra thyroid ism ( Alb rig ht he re d ita ry O ste od ystrop hy ) is due to defective G Protein in target tissue with
resultant resistance to PTH which cause | PTH, + Ca++, | Ph.
* Vit D De fic ie nc y Osteomalacia and Rickets .

Diet cholecalceferol 7 Dehydrocholecalciferol ( In skin through ultra voilet light )
+
25.OH. Choleca lciferol ( In Liver )
+
Kidney
.\ ( 1 o Hydroxylase ) ( |PTH, +Ca++, +Ph )
1,25 hydrocholecalciferol 24,25 (OH)2 Choleca lciferol

* Remember | PTH, + Ca++, and + Ph have positive stimulating effect on enzyme 1o Hydroxylase hence it activity.

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* Zona G -- Mineralcorticoids (Aldosterone)
Zona F -- Glucocorticoids (Corticosteroids)
Zona R -- Androgen (Testosterone, Estradiol)

** Cholesterol
+ 17 o Hydroxylase 17 . 20 Lyase
Pregnenolone 17 Hydroxypregnenolone Dehydroxyandrosterone

+ 3 | hydroxysteroid Dehydrogenase + 3 | hydroxysteroid dehydrogenase + 3 | hydroxysteroid dehydrogenase
Progesterone Hydroxyprogesterone Androstenidione
17, 20 lyase 17| Osteroid dehydrogenase
+ 21 | hydroxylase 21 | hydroxylase + + and Aoma ta se
11 Deoxycorticosterone 11 Deoxycortisol Testosterone / Estradiol

+11| Hydroxylase + 11| Hydroxylase
corticosterone Cortisol

ATII & K+ + Aldosterone synthase
Aldosterone .

* G luc oc ortic oid s :- CRH (from paraventricular nuclei) ACTH (AP) . (Both synthesize by POMC).
Release in circardian rhythm, Cortisol | at 6 AM and + at 12 midnight.
* ACTH up regulate its own receptor. Cortisol cause -ve feed back inhibition to both CRH and ACTH.
* Glucocorticoids are essential in response to stress. | cortisol level cause bone resorption.

* G luc oc ortic oid Func tions :- 1. Gluconeogenesis :- | protein catabolism and + protein syn.
| lipolysis
+ glucose utilization (hyperglycemic)
2. Anti inflammatory :- syn of lipocortin
inhibit phospholipase A2
inhibit IL2 ( so inhibit T.cell proliferation )
inhibit histamine and serotonin.
3. Maintain vascular responsiveness to catecholamine.

* M ine ra lc ortic oid s :-
* Hypovolemia | Renin ATI ATII | Aldosterone | Na + re a b sorp tion, | K+ se c re tion, | H+ se c re tion.
* Hyp e rka le mia cause | Aldosterone secretion.
* And roge ns :- Androstenidione produce Testosterone in testes and Estraidol in ovary.
+ Deficiency of 17, 20 lyase Ab se nc e of And rog e n.
+ Deficiency of 3 | hydroxysteroid dehydrogenase Ab se nc e of e ve ry thing .
+ Deficiency of 21 | hydroxylase Ab se nc e of G luc oc ortic oid s a nd M ine ra lc ortic oid s.
+ Def of 11 | hydroxylase Ab se nc e of Cortisol only ( b e c a use 11- d e oxyc ortic oste rone ha s p a rtia l Ald oste ro ne a c tivity 3% )
6

* Pa tholog y :- 1. Ad re noc ortic a l Insuffic ie nc y ( Ad ison d is) .
+Prima ry - Commonly cause by autoimmune destruction of Adrenal cortex.
- + glucocorticoids, mineralcorticoids and androgen | POMC, | ACTH.
- Hypoglycemia, hyperpigmentation, vol contraction, hyperkalemia, metabolic acidosis Aldosterone def.
+Se c ond a ry - Caused by + ACTH .
- Does not exhibit vol contraction, hyperkalemia, metabolic acidosis because aldosterone is normal.
2. Ad re noc ortic a l Exc e ss . | cortica l & androgen level, hyperglyc emia, muscle wasting, c entral ob esity, moon fac e buffa lo hump,
suprac lavicular fa t, poor wound healing, striae, hypertension, osteoprosis, virilization of fema le.
+ C ushing $ commonly cause by Glucocorticoid therapy and adrenal gland hyperplasia.
+ C ushing Dis Overproduction of ACTH.
3. Hype ra ld oste ronism (Conn $) -- cause by tumor.( hyp ertension, hypokalemia, metabolic a lkalosis, + renin secretion )
4. Wa te r house Frid e ric hson $ :- Catastrophic adrenal insufficienc y due to hemorrhagic necrosis of adrenal c ortex often because
of Meningococca l meningitis.
5. Ad re nog e nita l $ :- 21 | hyd roxyla se d e fic ie nc y -- - + Cortisol and Aldosterone.
- | Hydroxyprogesterone and progesterone.
- | ACTH hyperplasia of Zona F and Zona R .
- | Adrenal androgen.
- Virilization of female (early linear growth, pubic and axillary hair).
- suppress gonads function in both sexes.
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* End oc rine Pa nc re a se :- o cells ---- O ute r c e ll isle t ---- Glucagon
| cells ---- C e ntra l isle t ---- Insulin
o cells ---- Inte rmix ---- Somatostatin, Gastrin.
+ Pa nc re a tic polyp e p tid e :-
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
v Insulin ( Tyrosine kina se re c e p tor) stimula tion for se c re tion O ve r a ll Effe c t
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
| blood glucose + blood glucose
| AA
| Fa tty a cid
Glucagon
GIP ---------------------------------------------- + AA
GH ---------------------------------------------- + Fa tty a cid
hypokalemic Cortisol ---------------------------------------- + Ketoa cid
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v G luc a g ons ( c AM P me c h ) Stimula tion for se c re tion O ve r a ll Effe c t
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+ Blood glucose | Blood glucose
| AA
CCK ---------------------------------------------- | Fa tty acid
EN, Nor EN, Ac h ------------------------------- | Ketoacid ( | Hydroxubutyra te and a cetoaceta te )
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
* G luc a g on act only on liver Glycogen break down.
Glucagon + Fruc tose 2,6 Bip hosp ha te p roduc tion a nd + Phosp hofruc tokina se a c tivity.
( Tha t's why also cause gluconeogenesis, in addition to Glycogenolysis, Lipolysis, and Ketone produc tion).
* Insulin consist of o subunit and | subunit among which | subunit have tyrosine kinase activity.
* Insulin d own re g ula te s its own re c e ptor. Receptor | in starvation and + in obesity.
Ac tion :- | uptake of glucose and promote glycogen formation.
Inhibit Glycogenolysis and + Gluconeogenesis.
Decreases Fatty acid , ketones, AA, and serum K+ concentration
Inhibit lipolysis and stimulate fat deposition.
* Insulin def into hypokalemia, hypotension and noc turia. Also ketosis which results into metabolic acidosis compensa tory hyp erventila tion.
* Soma tosta tin :- Inhibit secretion of Glucagon, Insulin, Gastrin, and Intestinal absorption of Glucose.
* insulin secretion is media ted by ca++ channel op ening in | c ell. + Blood glucose, soma tosta tin and EN, Nor EN + insulin secretion.

7

* Te stoste rone synthesize by 5 o reductase and secreted by Leydig cells.

Cholesterol d esmolase
Cholesterol Pregnenolone
| +
LH 17 hydroxypregnenolone
+
Dehydroxyandrosterone
+
Androstenidione
17 | OH steroid Dehydrogenase +
Testosterone
5 o reduc tase +
Dihydrotestosterone (ac tive form)

( Inhib in re le a se from se rtoli c e lls, it c a use - ve fe e d b a c k a ffe c t on the re le a se of FSH from Ant p ituita ry )
* G nRH originate from arcuate nuclei of hypothalamus & secrete in pulsatile manner.
G nRH up re g ula te its own re c e ptor in AP.
Te stoste rone Ac tion :- * Prenatal differentiation of wolfian duct and external genitalia.
* Develop male Secondary sexual characteristics at puberty.
* Cause pubertal growth spurt.
* Maintain spermatogenesis (by paracrine effect of testosterone) and increases libido.
* | Size and secretory activity of epididymus, Vasdefrens, prostate and seminal vesicle.
* 5 o reductase inhibit by Finastride it can be used in BPH.
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* ESTRO G EN AND PRO G ESTERONE :-
HT GnRH AP
* FSH a nd LH Cause Steroidogenesis in ovarian follicle & corpus luteum. .\
Follicular development beyond the antral stage. LH FSH
Ovulation + +
Leutinization Theca c ell Granulosa c ell
+ + aroma tase
Testosterone ( Androgen ) Estrogen
(convert And rogen into estrogen)

LH FSH
Cholesterol Pregnenolone 17 Hydropregnenolone dehydroepiandrosterone androstenidione testosterone
(theca cell) Aroma tase
17| estradiol. (granulosa c ells)

* Aromatase convert testosterone into 17| Estradiol.
* In male FSH cause sp erma togenesis in sertoli cell where as in fema le it cause 17| Estradiol synthesis in granulose c ell.
* In male LH hormone ca use testosterone synthesis in leydig cells where as in fema le it cause testosterone synthesis in theca c ells.
* Estrog e n Func tion :-
1. - ve and + ve feed back effect on FSH and LH secretion. ( where as progesterone cause - ve feed back )
2. Maintainance and Maturation of fallopian tube, uterus, cervix, and vagina.
3. Development of female sec sexual characterstics.
4. Development of breast.
5. Upregulate estrogen, LH, and progesterone Receptor.
6. Development and proliferation of granulose cell.
7. Maintain pregnancy.
8. Lower uterine threshold to contractile stimuli during pregnancy vs.(progesterone Raise uterine threshold to contrac tile stimuli
during pregnancy)
9. Stimulate PL secretion but block its action on breast.
8

* Proge ste rone Func tion :-
1. - ve feed back effect on FSH, LH. ( where as estrogen cause both - ve and + ve feed back )
2. Maintain secretory activity of uterus in luteal phase.
3. Maintain pregnancy.
4. Raise uterine threshold to contractile stimuli during pregnancy vs.
Estrogen Lower uterine threshold to contractile stimuli during pregnancy.
5. Responsible of development of breast.

+ ve & - ve FEED BAC K C O NTRO L O F M ENSTRUAL C YC LE.
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Pha se of C yc le Horm one Ty p e of Fe e d Ba c k Site
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Follicular Phase Estrogen - ve AP
Mid Cycle Estrogen + ve AP (ovula tion occur)
Lutea l Phase Estrogen - ve AP
Progesterone - ve HT
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Fig:

* M e nstrua l c yc le :-
1. Follic ula r p ha se ( d a y 5 - 14) :- In which Primodial follicular development and uterus proliferate.
Estradiol | steadily and FSH, LH suppressed And Progesterone is low.

2. Ovula tion ( d a y 15) :- Occur 15 days prior to menses regardless of cycle length.
Estradiol + ve feed back on FSH, LH ( re sponsib le for LH surg e ) .
Ovulation occur as a result of estrogen induced LH surge.
Estrogen + just after ovulation and | again in leuteal phase ( sourc e of this | is c orp us le ute um)
Cervical mucous | and become less viscous.

3. Le ute a l Pha se ( d a y15 - 28) :- Corpus leuteum develop and syn of estrogen and progesterone occur from it.
| vascularity and secretory activity of endometrium..
Basal body temp | (progesterone act on HTthermoregulatory center)
If fertilization not occur corpus leuteum regresses + Estradiol and Progesterone.
If fertilization occur Estradiol and progesterone keep | steadily.
4. M e nse s ( d a y 1 - 4):- Is sloughing of endometrium because of with drawal of Estradiol and progesterone.
----------------------------------------------------------------------------------------

9

* PREG NANC Y :-

* 1
ST
TRIMESTER :- HCG stimulates corpus leuteum to produce Estradiol and progesterone.
HCG peak occur at week 9 and than it declines.

* 2
nd
& 3
rd
TRIMESTER : Progesterone produce by placenta & estrogen produce by fetal adrenal gland & placental
Interplay. Major Placental Estrogen is Estriol.
HPL (Human Placental Lactogen).has GH and PL like effect produce through out pregnancy

* PARTURITION :- Initiating event is unknown. (there is no change of blood oxitocin level prior to labor even though it is
potent stimulator of uterine contraction)
* LACTATIO N :- PL | steadily during pregnancy but estrogen and progesterone block the action of PL on breast.
After parturition estrogen and progesterone + and lactation occur.
Ovulation is suppressed by PL because PL inhibit GnRH secretion from HTwith resultant + in FSH and LH.
PL also antagonise the action of FSH and LH on ovaries.
Suckling stimulates both oxitocin and PL secretion.
---------------------------------------------------------------------------------------------

G I PHYSIO LO G Y
* STRUC TURE AND INNERVATIO N :
Epithelial cell may be secretive or absorptive.
M usc ula ris muc osa --- contraction cause change in surface area.
C irc ula r musc le --- contraction cause decrease in diameter of the lumen.
Long itud ina l musc le --- contraction cause shortening of GI segment.
Sub muc osa l p le xus a nd M ye nte ric p le xus -- is enteric nervous sys which integrate and coordinate the motility,
secretion and
Endocrine function of GI tract.
Fig:

* INNERVATIO N O F G I TRAC T :- consist of extrinsic nervous sys and intrinsic nervous sys.
Extrinsic ne rvous sys:- Comprise of Sympathetic and Parasympathetic nervous sys.
Parasym is Excitatory via vagus & pelvic nerves where as sym is inhibiting originate from T8 - L2.
( Vagus supplies to esophagus , stomach, pancreas & upper large intestine where as p elvic supp lies to lower large intestine, rec tum and anus )
10

Preganglionic cholinergic fiber synapse in prevertebral ganglion.
Post ganglion adrenergic fiber synapse in submucosal and myenteric plexus.
Some direct post ganglionic adrenergic innervation to blood vessel & smooth muscle also
occur here.
Intrinsic ne rvous sys:- Intrinsic sys relay information to and from GI to CNS.
Intrinsic sys also relay information with in GI by local reflexes.
Myenteric plexus (Auerbac h,s plexus) control motility of smooth muscle
Submucosal plexus (Meissner,s plexus) receive sensory information from chemo and mechano
receptor and control secretion and blood flow.
* G I HO RM O NES :-
Hormone s ( only 4) ---------- Gastrin , CCK, Secretin, GIP --- It enter portal and sys circulation and act on distal sites.
Pa ra c rine ( only 2) ----------- Somatostatin and Histamine --- Release from GI cells and act on short distance.
Ne uroc rine ( only 3) - - - - - - - VIP(vosotive intestinal peptide), Gastrin releasing peptide (Bomb esin), Enkephalin (met E, leu E)
Neurocrine synthesize in neuronal body move down by axons & release by nerve action potential.

* Gastrin ---- Little gastrin have 17 AA. Big gastrin have 34 AA (it is not a dimer of little gastrin).
Gastrin s 4 C terminal AA contain biologic activity.
Gastrin is a potent H+ releaser than histamine.
CCK also has gastrin like activity .
* Secretin --- all AA require for biologic activity.

----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Horm one s Homolog y Site of se c re tion Stimulus for se c re tion Ac tion
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Gastrin CCK G Cell (stoma ch) Sma ll p ep tide, AA specially | gastric H+ secretion.
Phenylalanine and Tryp tophan stimula te growth of gastric mucosa.
are potent stimula ter. (prietal c ell, mucosa of intestine & colon)
Distention of stoma ch .
Vagus via GRP.(a tropin does not inhibit Gastrin release b ecause
mediator of gastrin release is GRP not Ach)
Inhibit by H+ in stomach via Soma tosta tin.

CCK Gastrin I cell of Small p eptide a nd AA. Contra c tion of gallbladd er & relax sphinc ter of oddi.
(33AA) doud enum & fa tty a cid. Secrete pancrea tic enz.
Jejunum monoglyc erides. Secrete pancrea tic HCO3 via secretin.
(but not triglycerid es) Growth of endocrine pancrease & gall bladder mucosa.
Inhibit gastric emp tying.

Secretin Glucagon Scell doudenum H+ and fa tty acid in Doud enum Stimula te pancrea tic HCO3 and H2O secretion.
Stimula te biliary HCO3 secretion.
| growth of exocrine pancrease.
Inhibit H+ secretion.
Inhibit gastrin on growth of gastric mucosa.
(Gastric Inhibitory p ep tide)
GIP Secretin Doud enum and Fa tty ac id, AA, & Ora lly ad ministered Stimula te insulin release.
Glucagon jejunum Glucose. Inhibit H+ secretion.
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

* G I p a ra c rine : Soma tosta tin -- Secreted in response to H+ through out GIT, & its secretion is inhibited by vagus nerve.
Somatostatin inhibits all GI hormone and gastric H+ secretion
Hista mine ------- Secrete by mast cell induce gastric H+ secretion
Histamine also potentiate its effect on Ach and gastrin | H+ secretion.
* G I ne uroc rine s: VIP Cause GI smooth muscle relaxation, stimulate pancreatic HCO3 secretion & inhibit Gastric H+
secretion. VIP producing pancreatic tumor of islet cell pancreatic cholera
G RP (bombesin) -- release from nerve ending by vagal stimulation stimulate Gastrin release.
Enke p hlins -- Contract GI smooth muscle of lower esophageal, pyloric, and iliocecal sphincter.
Enkephlins also inhibit intestinal secretion of fluid and electrolytes.

11

* G I M OTILITY :- Contractile tissue of GITis unitary smooth muscle except pharynx, upper 1/ 3 of esophagus and
external anal sphincter which are straited muscle.
Pha sic Contra c tion ---- contraction and relaxation found periodically in esophagus, antrum and intestine.
Tonic c ontra c tion ------- found in lower esophagus sphincter, orad stomach, iliocecal and internal anal sphincter.
* Slow wa ve are osc illa ting me m pote ntia l which is essential to smooth muscle.
* Slow wave are not action potential but they do determine the pattern of action potential and contraction.
* Depolarization of slow wave bring mem potential closer to threshold to initiate action potential.
* Frequency of slow wave not influence by neuronal or hormonal input where as action potential yes.
* Frequency of slow wave lowest in stomach (3/ min) and highest in doudenum (12/ min).

* SALIVA :- There are 3 major glands, Parotid, maxillary and sublingual gland.(myoepithelial a nd duc ta l cells contrac t to ejec t
saliva in mouth)
* At lowest flow rate saliva has lowest osmolarity & | K+ conc vs.
At highest flow rate saliva has osmolarity close to plasma.
* The Acinus produce initial saliva whose composition is same as plasma but duct modify the saliva by reabsorbing
Na+ and cl- and secreting K+ and HCO3.( Aldosterone ac t on duc tal c ell | reabsorp tion of Na+ and secret K+ )
* Duct is relatively impermeable to water hypotonic saliva
* Parasympa thetic stimula tion is through facia l nerve VII and glossopharyngeal nerve IX | produc tion of sa liva (rec ep tors are muscarinic and
2
nd
messenger is IP3 where as sympa thetic stimula tion also cause | produc tion of saliva but rec ep tors are | and 2
nd
messenger is c AMP.

* SWALLO WING REFLEX coordinated in medulla. vs. vagus & glossopharyngeal nerve carry info to & from the medulla.
* During swallowing beathing inhibit, nasopharynx close, perstalsis begin, larynx elevate (glottis close), upper
esophageal sphincter relax (gravity accelerate the movement).
* At rest intraesophegeal P is < than atmospheric P, Intrathoracic P can be measured by baloon catheter.
* Primary peristalsis create just behind the food and secondary peristalsis clear the esophagus.
* Lower esophageal sphincter relax (via vagus nerve neurotransmitter is VIP) at the same time Orad stomach relax
(receptive relaxation) CCK participate in it by increasing dispensability of Orad stomach.

* G a stric re flux ---- occur when tone of esophageal sphincter + or secondary peristalsis does not clear food particles.
* Ac ha la sia ---- when lower esophageal sphincter does not relax, in turn food accumulates in esophagus.
* O ra d re g ion ---- contain Oxyntic gland vasovagal reflex relax Orad region. (Oxyntic gland secrete Hc l and Intrinsic fa c tor)
* C a ud a d re g ion ---- contraction, mixing occur and food propel to doudenum.

* M IG RATING M YO ELEC TRIC C O MPLEX :-
* Are contraction that occur at 90 min interval during fasting which clear stomach. Motilin cause those contraction.
* Gastric emptying is fast when contents are isotonic and is slow when contents are hypertonic or fatty.
* H+ in doudenum inhibit gastric emptying by direct neuronal reflex via GI plexus.
* Se g me nta l c ontra c tion mixing of contents in orad and caudad direction but no net movement of food occur .
* Pe rista ltic c ontra c tion coordinated by enteric nervous system & propel food downward.( contrac tion behind bolus
and relaxation in front of bolus )
* G a stroile a l re fle x deliver intestinal content in colon. Reflex mediated by ANS and gastrin.
* Ha ustra is a sac like segment appear following segmental contraction of colon (during mixing the colon content).
* Once rectum is filled about 25% cause urge to defication (it can be prevent by voluntarily by external sphincter).
* Va lsa lva ma ne uve r :- voluntary increasing of intraabdominal P by expiring against closed glottis.
* Food in stomach | gastro colic reflex | frequency of mass movement.
* Parasympathetic activity cause rapid gastrocolic reflex whereas CCK & Gastrin slows down the gastrocolic reflex.
* G a stroc olic re fle x : Is food in stomach which | the motility of the colon and frequency of mass movement.

12

--------------------------------------------------------------------------------------------------------------------------------------------------------------------------
G I SEC RETIO N C O NTENTS STIM ULATED BY I NHIBITED BY
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Saliva | HCO3 , | K+ IP3 parasympa thetic (imp) Sleep
Hypotonic c AMP sympa thetic ( | ) Dehydra tion
o a mylase (starch) Atropine (anticholinergic)
Lingual lipase (triglyc erides)
Kellikrein
Gastric HCl Gastrin, Ac h, + PH of stomac h
Hista mine (H2) via c AMP Chyme in doud enum
Atropine, Cemetidine, vagotomy, omeprazole
Pepsinogen parasympa thetic
Intrinsic fa c tor
--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
C ELL TYPE SITE PRO DUC T STIM ULUS FO R SEC RETIO N
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Oxyntic (parieta l c ell) Fundus HCl Gastrin, Hista mine, Ac h (vaga l)
Intrinsic fac tor
Chief cell (p ep tic cell) Fundus (Body) Pepsinogen Ac h (vagal stimula tion)
(convert to pepsin a t low PH)
G cell Antrum Gastrin see above
Mucous c ells Antrum mucous, pepsinogen Ach (vaga l stimula tion)
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

* G a stric Se c re tions --- HCl is secreted by parietal cell into lumen of stomach and HCO3 absorbed in blood stream
and HCO3 absorbed in venous blood (Alkaline Tide) later it secreted back into the lumen of the GI tract via
pancreatic secretion to neutralize H+ in small intestine.
Fig:

* Chief cells secret Pepsinogen in the form of zymogen granules.
* When stomach is empty its PH is < 3.0 inhibition of gastrin release, which further inhibit H+ secretion via
somatostatin.
* Chyme in the doudenum inhibit H+ secretion directly or via hormone GIP (release by fatty acid in stomach) &
Secretin (release
by H+ in duodenum).
* In gastric ulcer H+ is lower than normal and Gastrin is |.
* In duodenal ulcer H+ is higher than normal, Gastrin is high | and Gastric perital cells are | because of gastrin
mediated growth.
* Zollinger Ellison $ --- Gastrin secreting tumor of pancreas | H+ secretion & is not subject to - ve feedback
inhibition of H+.
* In vomiting H+ is lost and results into Metabolic Alkalosis (arterial Blood become Alkaline)
---------------------------------------------------------------------------------

13

* PANC REATIC SEC RETIO N :-
* Pancreatic juice is high in vol having same Na+, K+ conc as plasma where as HCO3 conc is higher than plasma,
and Cl- conc is lower than plasma.
* Pancreatic juice has isotonicity. It contain lipase, amylase, protease.
* Aqueous component is varies with flow rate.
* Na+, K+ conc is not effected by flow rate ( vs. saliva )
* At low flow rate HCO3 is low and Cl- is high where as At high flow rate HCO3 is higher and Cl- is low.
* The Acinar cell produce initial pancreatic juice Na+ and Cl-, than Ductal cell modified it by secreting HCO3 and
absorbing Cl- ( HC O 3 - C l e xc ha nge ) . Pancreatic duct is permeable to H2O so make it isosmotic.

* Re g ula tion of Pa nc re a tic se c re tion :- It is regulated by secretin and CCK.
* Secretin acts on pancreatic ductal cell | HCO3 secretion (via c AMP) where as CCK acts on Pancreatic Acinar cell
| enz secretion (via IP3).
* Ach (via vagal reflex) stimulate enz secretion by Acinar cell in response to H+, small peptide, AA, fatty acid in
duodenum.
* Cystic Fibrosis --- Defect in Cl channel because of mutation in the Cystic fibrosis Transmembrane conductance
(CFTR) gene Which results into deficiency of pancreatic enz mal absorption (statorrhea).
-----------------------------------------------------------------------------------------------------

BILE SEC RETIO N AND G ALL BLADDER:-
* Bile contain bile salts, phospholipids, cholesterol, bile pigment(bilirubin).
* Bile salt are Amphiphatic having hydrophobic and hydrophilic portion.
* In water bile salt orient them selves around droplet of lipid and keep the lipid disperse in solution (emulsified).
* Bile salt form Micelles by covrering one fatty acid and two monoglycerides; pointing there hydrophilic portion into
the aqueous solution to make it soluble for absorption.
* Bile is produce by hepatocytes continuously (chloretic agent increase bile formation).
* primary bile acid (cholic acid and chenodeoxycholic acid) is syn in hepatocytes than conjugate it to glycine and
Taurine to form the respective bilesalt.
* Intestinal bacteria convert primary bile acid to secondary bile acid (deoxycholic acid and lithodeoxycholic acid).
* Gall bladder concentrate the bile by NaCl and HCO3 reabsorption where as water reabsorbs isosmotically.
C O NTRAC TIO N O F G ALL BLADDER :-
* CCK cause contraction of gall bladder & relax sphincter of Oddi. vs.
Ach cause only contraction of Gall bladder.
* Terminal ileum absorbes conjugated bile acid with Na+ by sec active transport.
* Bile depletion cause statorrhea, bile pool depletion and Anemia, for e.g. Due to ilieal resection or diseased ileum.
----------------------------------------------------------------------------------------------------

DIG ESTIO N AND ABSO RPTIO N :-
+ C ARBO HYDRATE - - Absorbs only in the form of monosaccharide (glucose, galactose, fructose).
* o Amylase (salivary and pancrea tic) hydrolyze 1,4 glycosidic bond in starch & yield oligosaccharides maltose, maltriose,
& o limit dextrin which is further hydrolyze to yield glucose, galactose & fructose by enz maltase, o dextranase &
sucrase (brush border enz).
* Lactase, Trehalase also yield monosaccharide form disaccharides.
* Glucose and galactose absorbs with Na+ as a sec active transport, where as Na - K pump at basolateral side
maintain IC Na+. If this pump is poisoned Glucose, galactose absorption stops.
* Glucose, Galactose entered the intestinal cell by Na+ dependant Sec active transport (Cotransport) later it
entered blood by facilitated diffusion.
* Fructose absorption in the intestinal cell occur by facilitated diffusion ( so can not absorb against its | gradient).
* Lactose intolerance occur when brush border lactase is + or absent lactose cant be absorb H2O remains in
lumen results in osmotic diarrhea.

14

+ PRO TEIN - - Absorbs as a AA, Dipeptide and Tripeptide in intestinal cell.
* End op e p tid a se hydrolyze interior peptide bond, vs. Exope ptid a se hydrolyse one AA at a time from C terminal .
* Pe p sin secreted as pepsinogen from Chief cells H+ converts it into pepsin.
* PH for pepsin is 1 3, PH more than 5 inactivate pepsin as in duodenum. Pepsin is not essential for protein digestion
* Pa nc re a tic p rote a se are secreted in inactive form which is activated by brush border enz. eg Tripsinogen is
converted to Trypsin (active form) by Enterokinase in small intestine.
* Dipeptide and Tripeptide must hydrolyse by cytoplasmic peptidase to AA prior to enter into the blood.
* Free AA, Dipeptide and Tripeptide absorb with Na+ as sec active transport than AA enters blood by facilitated
diffusion.
* Dipeptide & Tripeptide absorbs faster than free AA due to 4 separate carriers for acidic, basic, neutral & Imino AA
absorption.
* Pancreatic protease degrade each other and also absorbed along with dietary protein.
+ LPIPDS - - Absorbs as fatty acid, monoglycerides & cholesterol in the form of micelles. (Glycerol is hydrophilic & is not
contain in micelles)
* Lingual Lipase digest some lipids, stomach breaks lipid into droplets and intestinal bile emulsify it.
* Pancreatic lipase, cholesterol ester hydrolase & phospholipase A2 hydrolyze lipids into fatty acid, monoglyceride
& chlesterol.
* Intestinal cells reesterified Triglycerides, phospholipids with cholesterol and apoprotein form chylomicron & than
chylomicron transported out of cell by exocytosis in the lymphatics later chylomicron added to the blood via
thoracic duct.
* Abetalipoproteinemia is failure to synthesize Apoprotein | results in inability to transport Chylomicron out of cell.
(apoprotein is one of the constituents of chylomicron).
* Hyper secretion of gastrin | H+ secretion + PH in duodenum Inactivate pancreatic lipase Statorrhea.

ABSO RPTIO N O F ELECTRO LYTE AND WATER :- Occur by cellular and paracellular routes.
+Tig ht Junc tion are - Tight (impermeable) junction present in epithelium of colon.
- Leaky (permeable) junction present in epithelium of small intestine and gall bladder.

NaCl absorption ------- 1. Passive diffusion (Na+ channel) 2. Na+ glucose, Na+ AA co transport.
3. NaCl cotransport. 4. Na+ - H+ exchange.

* In colon Na+ channel are stimulated by Aldosterone.
* Na+ - K pump + IC Na+ conc on basolateral side.
* Cl- absorption accompanies Na+ absorption through out the GI tract by -- 1. NaCl co transport
2. Cl - HCO3 exchange
3. Cl diffuse passively by paracellular route.

* K+ absorbs by passive diffusion (via paracellular route in small intestine) where as K+ secreted actively by
aldosterone in colon In diarrhea K+ secretion is | in colon hypokalemia.
* H2O absorbs in small intestine and gall bladder osmotically. Where as colon is less permeable to water.

SEC RETIO N O F ELEC TRO LYTE AND H2O :- Secretive mechanism is located in Crypt. vs. absorptive mechanism is in Villi.
* Cl is primary ion secreted in intestinal lumen through Cl- channel (via cAMP) and Na+ follow Cl- where as water
follow them.
* Cholera toxin some E- Coli toxin activate adenylate cyclase at the basolateral mem of the crypt | IC cAMP
| Cl secretion Na+ and H2O follow Cl- Diarrhea.
VITAMINS :- Fat soluble vit absorbs along with lipid and water soluble vit absorbs with Na+ cotransport where as VitB12
together with Intrinsic factor absorbed in ileum.

* C a ++ :- Ca++ absorption depend on active vit D (1,25 dihydroxycholecalciferol). ( + vit D cause Rickets and Osteoma lacia )
* Iron :- Iron absorbes as heme iron ( bound to hemoglobin or myoglobin ) or as a free Ferrous (Fe++). In Intestine cells
Heme iron broke down to release iron which bind to Apoferritin and transport to blood than In blood it
bound with Transferrin which take iron to liver and store it. (Iron deficienc y is the most common cause of anemia)
------------------------------------------------------------------------------------
15

RENAL AND AC ID BASE PHYSIO LO G Y
* TBW -- 60% of body wt. ( TBW vol is measured by Titra ted H2O or D2O)
* ICF -- 2/ 3 of TBW and is measured by TBW - ECF. ( it contain K+, Mg++, Protein, Inorganic ph, ATP etc)
* ECF --1/ 3 of TBW a nd is measured b y sulfa te, inulin, or manitol. (it contain Na+, Cl-, HCO3).
* Plasma -- of ECF or 1/ 12 of TBW & is measured b y radioiodinated serum albumin RISA or evan blue.(it contain Albumin a nd Globulin etc )
* Interstitial fluid --- of ECF ( of TBW ) and is measured b y ECF - Plasma.
* Fluid Compartment -- is measured b y vol = a mount injec ted - a mount exc reted / conc in plasma.
-------------------------------------------------------------------

* RBF (renal blood flow) is 25% of cardiac out put.
* RBF remain constant over the range of arterial BP from 100 - 200 mmHg (auto regulation).
* RPF (renal plasma flow) measured by PAH clearance because PAH is both filtered and secreted by renal tubules.
* Rena clearance can be measured by C = UV/ P RPF = c PAH = [U] PAH V / [P] PAH

* GFR is 20% of renal plasma flow (RPF) 125ml/ min. G FR = [U] inulin V / [P] inulin.
* GFR is measured by Inulin clearance because Inulin is filtered but not reabsorbed or secreted by renal tubules.
* Both BUN and Plasma Creatinine | as GFR +.
* Filtration Fraction is the fraction of RPF that filter across the glomerular capillaries ( it is 0.20). thus 20% of RPF is filtered.
Filtra tion Fra c tion = G FR / RPF
* GFR can be expressed by Starling equation. G FR = Kf [ ( PG c - PBc ) - ( tG c - tBc ) ]

* PG c : -- is constant along the length of capillaries.
It | by dilatation of afferent arterioles &| by constriction of efferent arterioles.
* PBc : -- | by constriction or blockade of ureter + GFR.
* tG c :-- | along the length of glomerular capillaries. It | by | in protein conc + GFR.
* tBc : -- is zero small amount usually absorbs

* NaCl and Mannitol donot cross cell mem and confined to ECF,
* More water than salt lost during sweating.

----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
TYPE EXAM PLE EC F Vol IC F Vol EC F O smola rity Hc t, Se rum Na +
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
- Isosmotic Vol Expansion Isotonic Na cl infusion | No change No Change + Hc t , Na --
- Isosmotic Vol Contra c tion Diarrhea + No change No change | Hc t , Na --
- Hyp erosmotic Vol Contrac tion Swea t, fever, Diabetes Insipidus + + | Hc t (RBC shrunk) Na+ |.
- Hyp erosmotic Vol Expansion | NaCl intake | + | Hc t + ,Na+ | .
- Hyposmotic Vol Expansion SIADH | | + Hc t (RBC swell), Na+ +
- Hyposmotic Vol Contra c tion Adrenocortica l insufficiency (loss of NaCl) + | + | Hc t, (RBC swell) Na+ +.
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

* TRANSPO RT M AX CURVE FO R G LUC O SE :- Plasma glucose conc of < 300 mg/ dl can be absorbed by proximal tubule
through Na - glucose co transport.
* Threshold at which glucose first appear in the urine is approx 300 mg/ dl.
* SPLAY is the region of glucose curve b/ w Threshold and transport max. (300-350mg/ dl)
* At 300 - 350 mg/ dl --- spilling of gluc ose occ ur in urine b e fore sa tura tion or ( Tm) Transport maximum.

* Tm C URVE FO R PAH :- PAH filtration | as PAH plasma conc |.
* Secretion of PAH from Peritubular capillaries into tubular fluid occur in proximal tubule.
* PAH secretion | when plasma conc | once carriers become saturated it stops further | in secretion due to Tm.
* RPF is measured at plasma PAH conc below the Tm (Transport max).
* Relative Clearance: PAH > K+ > inulin > urea > Na+ > glucose > AA > HCO3-.

* Na + REG ULATIO N: Na+ in the tubular fluid (TF) in Bowman space equals that in plasma (P) is said to be TF/ PNa+ = 1.0
* If TF/ PNa+ is < 1 Net Reabsorption of solute occur dilution of TF.
* If TF/ PNa+ is > 1 secretion of solute occur produce concentrated TF.
16

* Only 1% of filtered Na+ is excreated.
* Na+ is reabsorbed by Co transport with glucose, AA, ph, lactate, K+ in proximal tubule.
* Na+ is reabsorbed also by Counter transport as Na+ - H+ exchange in PT.
* Na+ absorbed with Cl- in middle and late PT. (total of 67% of Na+ reabsorbed in PT)
* In Thick ascending limb of Loop of Henle 20% of Na+ reabsorbed as Na+ - K+ - 2Cl- Cotransport
also called diluting segment and is impermeable to H2O (loop diuretics act here).
* Distal tubule and Collecting duct together reabsorbe 12% of filtered Na+.
* Early Distal tubule is Cortical Diluting segment reabsorb Na+ by Na+ - Cl- Co transport. (Thiazide ac t here).
* Principle cell reabsorb Na+ & secrete K+ in late distal tubule (DT) & collecting duct. (Aldosterone/ ADH ac t here)
* Intercalated cell secrete H+ & reabsorb K+ in late DT& collecting duct. (Aldosterone also ac t here to secrete H+).
* Starling forc es in p eritubular capillaries (due to | or + in protein conc) | or + in proximal tubular reabsorp tion.

* K+ REG ULATIO N :- K+ is filtered, secrete & reabsorbed by nephron to achieve K+ balance.
* TF/ PK+ = 1 in Bowman space.
* PTreabsorb 67% of K+ alonge with Na+ and H2O.
* Thick ascending limb of Loop of Henle reabsorb 20% of filtered K+ as Na+ - K+ - 2Cl- Cotransport.
* Distal Tubule and collecting duct either reabsorb or secrete K+ depend on dietary intake.

SHIFT O F K+ b / w EC F AND IC F
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
C a use s of K+ shift out of c e ll ( hyp e rka le mia ) C a use s o f K+ shift into the c e ll ( hyp oka le mia )
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
* Insulin Deficienc y * Insulin
* | adrenergic antagonist * | agonist
* Acidosis ( via H+ - K+ exchange ) * Alkalosis ( via H+ - K+ exchange)
* Hyperosmolarity (H2O out of c ell K+ follow) * Hyposmolarity (H2O flow into the c ell K+ follow)
* Na+ - K+ pump inhibitor
* Excersize
* Cell lyses
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
EFFECT O F DISTAL K+ SEC RETIO N
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
C a use s of | d ista l K+ se c re tion C a use s of + d ista l K+ se c re tion
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
* High K+ diet * Low K+ diet
* Hyp eraldosteronism * Hypoaldosteronism
* Alkalosis * Acidosis
* Thiazide * K+ sparing Diuretics
* Loop diuretics * Renal failure
* Luminal Anion
--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

* Ure a Re g ula tion : 50% of urea reabsorb passively in PT. Other segment are impermeable to urea.
* ADH | urea permeability of inner medullary collecting duct which contribute urea recycling in the medulla.

* Phosp ha te Re g ula tion : 85% of phosphate reabsorb in PTas Na+ - phosphate Cotransport. Where as 15% excreted.
* PTH Inhibit phosphate reabsorption phosphaturia & | urinary cAMP. ( PTH also | bone resorp tion )
* phosphate is urinary buffer for H+ excretion of H2PO4 (titrableacid).

* C a ++ Re g ula tion : 90% of Ca++ reabsorbed in PTand Thick ascending limb of Loop of Henle.
* Loop diuretics cause | Ca++ excretion by inhibiting Na+ reabsorption. ( Tx of hypercalcemia )
* Thiazide + Ca++ excretion by reabsorbing Ca++ in distal tubule ( Tx of Hypercalciurea ).
* DTand Collecting duct reabsorb 9% of Ca++ actively.
* PTH | Ca++ reabsorption in DT.
* Mg ++ Re g ula tion : Reabsorb in PT, Thick ascending limb and DT
* In Thick ascending limb Mg++ and Ca++ compete for reabsorption.
* Mild + in Mg++ stimulate PTH secretion | Ca++ reabsorption.
* Severe + in Mg++ inhibit PTH secretion | Mg++ reabsorption.( also | Phosphate reabsorption )
17

* C O NC AND DILUTIO N O F URINE :-
* Cortic op a p illa ry osmotic g ra d ie nt :
* Is the gradient of osmolarity from cortex ( 300 mOsm / L) to papilla (1200 mOsm / L) & is comprise primarily of NaCl & urea.
* Vasa Recta (capillaries of Loop of henle) maintain the corticopapillary gradient by serving as osmotic exchanger.
* Thick Ascending loop of henle reabsorbe Na+ - K+ - 2Cl by cotransport & is permeable to H2O. [ TF/ Plasma osmo = <1 ]
* Early distal tubule is cortical diluting segment and is impermeable to H2O.
* In late distal tubule H2O permeability | by ADH. Here H2O reabsorb normally until TF/ Plasma Osmo = 1
* In collecting duct H2O permeability | by ADH. Here H2O reabsorb normally untill TF/ Plasma Osmo >1 .

HO RM O NES THAT ACTS ON KIDNEY:
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Hormne s Stimulus for se c re tion Time c ourse M e c h o f a c tion Ac tion on kid ne y
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
PTH + Plasma Ca++ Fast Ad enyla te Cyc lase + ph reabsorp tion (PT)
mild + in Mg++ c AMP (a t basola teral side) | Ca++ reabsorption (DT)
Stimula te 1 o hydroxylase in PT
ADH | Plasma Osmolarity Fast Ad enyla te c yclase | H2O p ermeability in la te DT&
+ Blood vol V2 Rec ep tors collec ting duc t (principle c ell)
Aldosterone + Blood vol (via renin AT) Slow New Protein Synthesis | Na Reabsorp tion in DT- Principle c ell
| Plasma K+ | K secretion in DT- Principle cell
| H+ secretion in DT- Interca lated c ell
ANF | Atrial Pressure Fast Guanyla te c yclase | GFR, + Na+ reabsorption
cGMP
Angiotensin + Blood vol (via renin) Fast IP3 mec h | Na+ - H+ exchange in PT
(stimula te Aldosterone synthatase)
| HCO3 reabsorption in PT
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

AC ID BASE BALANC E :
* Buffer prevent changes in the pH when H+ ions are added or removed. ( Buffer is most effective in the linear
portion of the titration curve.)
* Buffer are more effective with in 1.0 pH unit of the pK.
* Major EC buffer is HCO3. (pK of CO2/ HCO3 buffer is 6.1)
* Minor EC buffer is Phosphate (PK of H2PO4 / HPO4 2 buffer is 6.8)
* Major IC buffer is Hg. Deoxyhemoglobin is Better buffer than Oxyhemoglobin at physiologic pH.
* Minor IC buffer is organic Phosphate (AMP, ADP, ATP, 2,3 DPG)
* When pH of the solution is equal to pK than there are equal conc of HA- and A-.
* PH = pK + log [A-]/ [HA-] . (where A- is base of the buffer and HA- is acid of the buffer)

RENAL ACID BASE :
* Filtered HCO3 reabsorbs in proximal tubule in two steps
* | PCO2 | HCO3 Reabsorption ( because IC H+ is | )
* + PCO2 + HCO3 Reabsorption ( because IC H+ is + )
* ECF vol contraction | HCO3 Absorption (contraction Alkalosis) and produce acidic urine.
* ECF vol expansion + HCO3 Reabsorption .
* Angiotensin II stimulate Na+ H+ exchange | HCO3 reabsorption. (Contributing to Contraction Alkalosis)
-----------------------------------------------------------------------------------------------

* H+ secrete in the lumen by H+ - ATPase and resultant HCO3 is reabsorbed.
* Secreted H combine with filtered HPO4 H2PO4 (titrable acid). This Process results into net excretion of H+ in
urine.
* Another mech for excreting H+ is NH3 Production in renal cell from glutamine. ( NH3 produc tion | in Acidosis which favor H+
excretion ) H+ + NH3 NH4+ excreted in urine (diffusion trapping)

18

AC ID BASE DISO RDER:
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
DISO RDER C O 2 + H2O H + HC O 3 Re sp C omp e nsa tion Re na l C o mp e nsa tion
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Metabolic Acidosis + | + Hyp erventila tion | H+ excretion
| HCO3 rea bsorption
Metabolic Alka losis | + | Hypoventila tion | HCO3excretion
Respiratory Acidosis | | | None | H+ excret ion
| HCO3 rea bsorption
Respiratory Alka losis + + + None + H+ Excretion
+ HCO3 rea bsorption
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
* RULE : CO2 goes up HCO3 goes up CO2 goes down HCO3 goes down. ( Direc tly proportional rela tionship).
* Normal Serum Anion Gap is 10 - 16 mEq / L. ( Serum Anion Gap = [Na+] - [Cl-] - [HCO3-] )
* Synthesis of Glucose (gluconeogenesis) during prolong fasting also occur in kidney.
* H+ Excreted in urine as H+ + HPO4 -2 H2PO4 (Titrab le acid)
H+ + NH3 NH4+ (diffusion trapping)

-------------------------------------------------------------------------------------------------------------------------

RESPIRATO RY PHYSIO LO G Y
* LUNG VO LUM ES :
1. Tid a l Vol - - is the vol inspired and expired with each normal breath.
2. Insp ira tory Re se rve Vol ( IRV) - - is the vol that can be inspired over the tidal vol eg during exersize.
3. Exp ira tory Re se rve Vol ( ERV) - - is the vol that can be expired after expiration of the tidal vol.
4. Re sid ua l Vol ( RV) - - Vol that remains in the lung after max expiration. ( cant be measure b y spirometery ).

* Ana tomic De a d sp a c e -- Vol of conducting airway it is 150 ml normally. (measured by Fowler s Method )
* Physiolog ic De a d sp a c e -- vol of the lung does not eliminate CO2 normally or due to dis. ( measured by Bohr s Method )

* M inute Ve ntila tion = Tid a l Vol Bre a th / min
* Alve ola r ve ntila tion = Tid a l Vol De a d sp a c e Bre a th / min

* LUNG C APAC ITIES :
1. Insp ira tory C a p a c ity = Tid a l Vol + Insp ira tory Re se rve Vol.
2. Func tiona l Re sid ua l C a p a c ity ( FRC ) = Exp ira tory Re se rve Vol + Re sid ua l Vol (can not measured by spirometery)
3. Vita l C a p a c ity = Tid a l Vol + Insp ira tory Re se rve Vol + e xp ira tory Re se rve Vol
4. Tota l Lung C a p a c ity = Tid a l Vol + IRV + ERV + RV.

* Forc e d Exp ira tory Vol ( FEV) : Is air expired in one Second after Max Inspiration.
It is 80% of forced vital Capacity. FVC . FEV / FVC = 0.8
* In restrictive Lung Dis ( Fibrosis ) both FEV and FVC is reduced.
* In Obstructive Lung Dis ( asthma ) FEV reduces more than FVC.

* MUSC LE O F INSPIRATIO N : * MUSC LE O F EXPIRATIO N :
Diaphragm (normally) Passive (normally)
External Intercostal Muscle Abdominal & Internal Intercostal muscle ( during exercise )
Accessory Muscle ( during exercise )

* C OM PLIANCE :- The extent to which lung expand (stretchability) for each unit in Transpulmonary P is called the
Compliance.
| Compliance | Stretchability where as + compliance + stretchability. ( Comp lianc e measures stiffness of the lung )
( C ha ng e in Intra p le ura l P d uring insp ira tion is use d to me a sure d yna mic c o mp lia nc e of the lung )

19

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
* C a use s of + Lung Comp lia nc e * C a use s of | Lung C omp lia nc e
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
High Expanding Pressure Emphysema (+ Elastic fiber)
| Pulmonary venous return Age
Fibrosis
Lack of surfa c tant
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------

* Under equilibrium condition lung have a tendency to collapse which is exactly balance by tendency of chest wall
to spring out.
* HYSTERESIS :- Is inflation of the lung follow different curve than deflation of the lung.
* Compliance of the lung chest wall system is less than the lung alone or chest wall alone.
* In Emphysema lung compliance is | so FRC | too. This change disturb the lung chest compliance system, so the
lung chest wall system seek for higher FRC in order to balance these two forces again. This is the reason pt develop
barrel shape chest to provide new Vol to lung with results into + O2 diffusion.

* SURFACE TENSIO N O F ALVEO LI AND SURFAC TANT :
* Tendency to collapse alveoli is directly proportional to the surface tension and inversely proportional to alveolar
radius called La p la c e La w . ( large a lveoli has low tend ency to collapse than sma ller a lveoli ).
* Surfactant lines the alveoli and reduce the tension | compliance.
* Surfactant is made by Type II alveolar cells consist of Dipalmitoyl Phosphatidyl Choline.
* Neonatal RDScause by lack of surfactant Atelactasis (difficulty in reinflation due to + compliance) Hypoxemia
(V/ Q misma tch).

* AIRWAY RESISTANC E :- Airflow is directly proportional to pressure difference of the mouth and alveoli and inversely
proportional to airway resistance . (Airflow) Q = AP/ R ( where AP is pressure gradiant and R is Airway Resistanc e)
* Airway Resistance (R) is describe by Poise uille s La w . R = 8nl / t r4
Where n is viscosity of the inspired air, l is length of airway, and r is radius of airway.

* Fa c tor tha t c ha ng e Airwa y Re sista nc e :
* Parasym stimulation, Irritants, Slow reacting subs of anaphylaxis (constricts airway) + radius and | resistance
* Sympathetic stimulation dilates airways | Radius and + Resistance (via |2 recep tors).

* | Lung Vol exert more traction (pulling force) & + airway resistance. vs.
+ Lung Vol exert less traction & | airway resistance
For exa mple in Asthma p t learn to brea th a t high lung vol to off set the high resistanc e.

* Viscosity & Density changes the resistance to air flow : If density of gas | resistance to airflow | (eg deep sea diving)
If density of gas + resistance to airflow + (brea thing low density gas like helium)
* Medium size bronchi are major site of resistance.
* Small size airway do not offer | resistance because of parallel arrangement.
-----------------------------------------------------------------------------------------------

BREATHING C YC LE :- ( At rest before inspiration begin)
1. At Re st - - - Alveolar P equals atmospheric P ( alveolar P is said to be zero ).
Intrapleural P is - ve ( can be measured b y baloon ca theter in esophagus ) where as Lung vol is FRC.
2. During Insp ira tion - - Inspiratory muscles contract thorax Vol to |.
P gradient cause air to flow into the lung.
Intrapleural P become more - ve and lung Vol | by 1 tidal vol (+ FRC).
3. During Exp ira tion - - - Alveolar P become greater (+ ve) than atmospheric P.
Intrapleural P return to its resting value during normal expiration (passively).
During forced expiration Intrapleural P become +ve Lung vol return to FRC before another cycles begin.
( In COPD airway resistanc e is | & p t expires slowly with pursed lip to prevent airway collapse which occur with forc ed expira tion )
* G a s Exc ha ng e :- * Diffusion of gases such as O2 and CO2 depends in the partial P difference across the mem and
area available for diffusion. ( Can be measured by Da lton s Law Partial P = Total P Frac tional conc entra tion ).
20

* About 2% of Cardiac output bypass pulmonary circulation because of physiologic shunt that s why
mixture of the venous blood makes PO2 of arterial blood slightly less than alveolar air.
* Solubility of O2 in the blood is 0.3 ml/ 100ml of blood .

Blood g a se s va lue in norma l c ond itions:
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
G a s Dry Insp ira tion Humid Insp ira tion Alve ola r Air Sys Arte ria l Blood M ixe d V e nous Blo od
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
PO2 160 mmHg 150 mmHg (due to H2O in air) 100 100 % (slightly less) 40 mmHg
PCO2 0 40 mmHg 40 mmHg 46 mmHg
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

* Pe rfusion limite d e xc ha nge --- When gas equilibrate early along the length of pulmonary capillaries the partial P of
arterial blood become equal to partial P of alveolar air.
* Diffusion limite d e xc ha ng e - - - When the gas does not equilibrate fully by the time blood reaches the end of the
pulmonary Capillaries the partial P of arterial blood is less than that of alveolar air .
* Diffusion of O2 from alveolar air to pulmonary capillaries bed is usually perfusion limited but become diffusion limited
in dis. Eg In Fibrosis diffusion of O2 + because of thickening of the alveolar mem | diffusion distance. Where as in
Emphysema diffusion of O2 + because surface area for diffusion is +.
------------------------------------------------------------------------------------------------
O 2 TRANSPO RT :
* Hg contain 4 subunit 2o and 2| ( each subunit contain heme moiety which is iron containing porphyrin ) .
* Ferrous (Fe2+) state of iron bind O2 Where as ferric (Fe3+) state of iron is methemoglobin and does not bind O2.
* In fetal Hg | chain is replaced by chain.
* O2 affinity of fetal Hg is higher than adult because 2,3 diphosphoglycerate (DPG) bonds less avidly to fetal Hg. ( that
is why O2 movement from mother to fetus is facilitated ).
Hg O 2 DISSOC IATIO N C URVE :
* At PO2 of 100 mmHg Hg is almost 100% saturated.
* At PO2 of 40 mmHg 75% of Hg is saturated.
* At PO2 of 25 mmHg 50% of Hg is saturated.
* The affinity of 4
t h
O2 molecule is very high.

* Because the curve is almost flat in PO2 range from 60 - 100 mmHg, the human can tolerate change in atmospheric
P without compromising the O2 carrying capacity of Hg.

C HANG E IN O 2 DISSO CIATIO N C URVE :
1. Shift to the rig ht - - - Affinity of Hg for O2 + P50 | . ( C a use s a re |PC O 2, +PH, |Te mp, | 2,3DPG) .
* Adaptation of chronic Hypoxemia (high altitude) | 2,3DPG which bind to | Chain to facilitate unloading of O2 in
tissue. By + the affinity of O2 .
* | PCO2 and + PH + the affinity of Hg for O2 & facilitating the unloading of O2 in tissue as in exercise. ( Bohrs Effe c t )
2. Shift to the Le ft - - - Affinity of Hg to the O2 | P50 + unloading of O2 in tissue is more difficult .
* C a use s a re + PC O 2, | PH, + Te mp , + 2,3DPG .

C O 2 TRANSPO RT : CO2 carried to the lung in 3 Forms. 1. HCO3- ( 90% .major form )
2. Carbaminohemoglobin ( small amount )
3. Dissolved CO2 ( small amount )
* CO2 generate in tissue enter into venous plasma enter into RBC where CO2 combine with H2O by Carbonic
anhydrase H2CO3 H+ and HCO3-.
* H+ is buffered inside RBC (Deoxyhemoglobin) where as HCO3- is exchanged for Cl- by RBC (C loride shift).
* In lung all above reaction occur in reverse ( which is HCO3- enter into RBC in exchange for Cl- than HCO3-
combines with H+ H2CO3 which further decompose into CO2 and H2O and CO2 is diffuse out ).

* Pre ssure and Re sista nc e in pulmonary circulation is much lower than systemic circulation.
* Cardiac output (pulmonary) is equal to systemic circulation.

21

DISTRIBUTIO N O F PULM O NARY BLO O D FLO W --- Distribution of pulmonary blood flow effect by gravity.
* In supine position blood flow is uniform through out the lung where as standing position blood flow is lowest in apex.
BLO O D FLO W IN LUNG ZO NES :
+ Zone 1 - - Alveolar P > Arterial P > Venous P (b lood flow is lowest) -- V/ Q |. (| Alveolar P collapses the capillaries when arterial BP is low eg .In
Hemorrhage)
+ Zone 2 - - Arterial P > Alveolar P > Venous P (b lood flow is medium).
+ Zone 3 - - Arterial P > venous P > Alveolar P (b lood flow is highest) -- V / Q + .
* Hypoxia cause local vasoconstriction (Opposite effect of that in systemic circulation where hypoxia cause
vasodilation) . It is imp in lung because local vasoconstriction divert blood from poorly ventilated area to well
ventilated area.
* In fetus pulmonary vascular resistance is very high due to generalized hypoxic vasoconstriction as a result blood flow
through fetal lung is low . ( with first breath alveoli become oxygenated and vascular resistance decreases )
* Both ventilation and Perfusion is great in base than in apex. ? (very imp to understand)
* Right to left shunt normally occur to a small extent because 2% cardiac output by passes the lungs. More than 2% is
Usually due to congenital abnormality + in arterial PO2. Where as Left to right shunt | in venous PO2 (donot result
in a + in arterial PO2)

VENTILATIO N / PERFUSION RATIO :
1. Norma l V/ Q Ra tio = 0.8 ( 0.8 when tidal Vol & pulmona ry cardiac out put are normal, and it is liable for 100 mmHg of PO2 & 40 mmHg of
PCO2).
2. V/ Q is Ze ro when airway is completely blocked, Perfusion is normal and ventilation is Zero No Gas Exchange.
3. V/ Q is Infinity when blood flow is blocked and ventilation is normal No Gas Exchange.

* V/ Q is highest ( > 1.0 ) in the apex of the lung and lowest ( 0.8 ) at the base of the lung. (imp to understand)
* PO2 is greater than PCO2 in different region of lung. 1. At apex ---- PO2 | and PCO2 +
2. At base ---- PO2 + and PCO2 |
----------------------------------------------------------------------------------------
C O NTRO L O F BREATHING :-
1. M e d ulla ry Re sp Ce nte r:+Dorsa l Re sp ira tory G roup control inspiration & genera te basic rhythm of brea thing rec eive input from lung via
vagus & from peripheral chemorec ep tor via glossopharyngeal nerve where as it send output to diaphragm via
pherenic nerve .
+ Ve ntra l Re sp ira tory G roup control Expira tion & is not ac tive during norma l brea thing because Expiration is passive
.
2. Ap ne ustic c e nte r - - - - - - - - - - - - - located in the lower pons . It stimula te inspiration more d eep er and prolongs Inspira tory gasp. (Apneusis)
3. Pne umota xic Ce nte r - - - - - - - - - located in the upper pons. It inhibit inspiration therefore regula te inspira tory Vol and ra te.
4. C orte x - - - - - - - - - - - - - - - - - - - - - - - - - Breathing can be und er voluntary control.
----------------------------------------------------------------------------------------

C HEM O REC EPTO RS FO R O 2, CO 2, & H+ :-
1. C e ntra l C he more c e ptors of the me d ulla is sensitive to PH of CSF.
* H+ does not cross the BBB but CO2 does. So when CO2 enter CSF combine with H2O H2CO3 H+ + HCO3-
(by carbonic anhydrase) than liberated H+ can act directly on central chemoreceptors. ( that s why | or + in CO2
cause change in breathing).

2. Pe rip he ra l c he more c e ptors present in Carotid and Aortic bodies. (stimulate by + PO2, |PCO2, H+)
* When Partial PO2 falls < 60 mmHg | breathing rate by peripheral chemoreceptors.
* When PCO2 | | in breathing rate.
* H+ ion stimulate carotid bodies chemoreceptors directly and is independent of PCO2 . eg Metabolic Acidosis |
the breathing rate ( where PCO2 is low).

O THER RECEPTO RS THAT C O NTRO L BREATHING RATE :
1. Lung Stre tc h Re c e ptors ( He ring Bre ue r Re fle x ) stimula te b y distention of lung | in brea thing ra te.
2. Irrita nt Re c e ptors located in b/ w airway epithelial c ells. It stimula te b y noxious stimuli eg a mmonia, smoke etc.
3. J Re c e ptors located in a lveolar wall c lose to capillaries it stimula ted b y capillaries engorgement as in LHF Rapid shallow breathing.
4. Joint a nd M usc le Re c e ptor | Brea thing during (early) exercise.

22

INTEG RATED RESPO NSE O F RESPIRATO RY SYSTEM DURING EXERCISE :
* | O2 consumption and |CO2 production
* | ventilation rate
* No change in arterial PO2 and PCO2 where as Venous PCO2 |.
* PH stays normal during moderate exercise where as PH + during strenuous exercise due to lactic acid production.
* Pulmonary blood flow |. V/ Q rate more evenly distributed through out lung

ADO PTATIO N TO HIG H ALTITUDE :
* Alveolar PO2 + and Arterial PO2 also +.
* Ventilation rate |.
* Arterial PH | ( | Respiration cause Alkalosis )
* Hg conc | ( because | erythropoietin production )
* 2,3 DPG conc | ( facilitate unloading of O2 in tissue ).
* Hg O2 dissociation curve shift to the right side (Bohr s effect), + affinity of Hg for O2 and facilitate unloading O2.
* Pulmonary vascular resistance | (vasoconstriction).
-----------------------------------------------------------------------------------------------------------------

C ARDIO VASC ULAR PHYSIO LO G Y
* Stre ss Vol is the blood in systemic arteries which are thick walled.
* Arterioles are the site of high resistance and is innervated by autonomic fibers.
* Capillaries comprise of largest total cross sectional area and surface area.
* Unstre ss Vol is the blood in systemic veins and have lowest P.
* Ve loc ity of b lood flow is directly proportional to blood flow & inversely proportional to cross sectional area. v = Q / A
* Blood flows from high P to low P & is inversely proportional to resistance of the blood vessel. Q = AP/ R (Q= Flow, A= area)
* Re sista nc e is directly proportional to the blood viscosity & length of the vessel and inversely proportional to the 4
t h

Power of the vessel radius ( Poise uille s La w ) . R = 8ql / tr4 ( q is viscosity and l is length of vessel )
* Re nold s No: Renolds No predict whether flow is laminar or turbulent. As renold No | the tendency of turbulence|.
+ Blood viscosity ( due to anemia, + Hematocrit) | the Renold No Turbulence. ( produce audible bruits )
| Blood viscosity (eg. in narrowing of vessel, polycythemia) | the renold No turbulence. (produce bruits )

* C a p a c ita nc e ( c omp lia nc e ) describes the distensibility of the blood vessels & is directly proportional to Vol &
inversely proportional to P. C = V/ P ( V is volume where as v is flow )
* Compliance is much greater in arteries. Compliance + as person ages. ( C omp lia nc e + Pulse P | )
* Blood flow P falls over its course due to changing resistance of vessels (that s why P is highest in aorta than in vena cava).
* Largest fall of P occur across the arterioles since arterioles are the site of the highest resistance.
* Arte ria l Pre ssure is pulsatile and not constant during cardiac cycle.
1. Systolic P : is highest arterial P during cardiac cycle (heart contracts)
2. Dia stolic P : is the lowest arterial P during cardiac cycle (heart relaxes)
3. Pulse P : is difference b/ w systolic and diastolic P and is determined by stroke Vol ( stroke Vol | Pulse P | )
+ in capacitance (compliance) such as with aging results in | Pulse P.( C omp lia nc e + Pulse P | )
4. M e a n Arte ria l P: is average Arterial P with respect to time calculated by Dia stolic P + 1/ 3 of Pulse P.

ELEC TROC ARDIO G RAM :
P wa ve - - Atrial depolarization ( shows the size and thic kness of a trium)
PR inte rva l - - Interval b/ w atrial depolarization & ventricular depolarization. It is starts from beginning of P wave till the
beginning of Q wave. (PR interval | when conduction velocity is slow due to heart block). NL time 0.21
Q RS c omp le x - - is Ventricular Depolarization it also buried Atrial Repolarization. Normal time 0.12
Q T inte rva l - - is beginning of Q wave till the end of Twave. It represent entire depolarization & Repolarization of
ventricle. Normal time 0.41 ( shows the size and thickness of ventric le)
ST se g me nt - - Is segment from the end of Swave till the beginning of Twave. It is isoelectric period shows entire
ventricular depolarization.
T wa ve - - is ventricle Repolarization.

23

C a rd ia c AP: Na - K ATPase maintain ion gradient across cell mem. (AP are of longer dura tion in ventric le 300 m sec)
Pha se 0 : Up stroke, | inward Na flow depolarization (at the peak of AP the mem potential is equilibrium potential for Na+).
Pha se 1 : Initial repolarization caused by + inward Na+ flow and initial K+ outward flow ( it is brief period ).
Pha se 2 : Transit | in inward Ca++ flow & | outward K+ flow result in Pla te a u (outward & inward c urrent are approx same during
this p eriod)

Pha se 3 : Is repolarization in which inward Ca++ conductance + and outward K+ conductance |. | outward K+
conductance hyperpolarize the mem (equal to K+ equilibrium potential) and than resting mem potential.
Pha se 4 : Resting mem potential ( inward outward current is equal ). Resting mem potential is determined by conductance
to K+ and approaches K+ equilibrium potential.
Sinoa tria l Node ( SA) :
* It is Pace maker and does not have resting mem potential ( it exhibit Phase 4 Depolarization )
* AV Node and HISPurkinji system are latent pace maker. It can over ride SA node if SA node is not functioning.
* The intrinsic rate of Phase 4 depolarization (heart rate) is slower in AV node and HIS purkinji system than in SA node.
Pha se 4 : Slow depolarization -- | inward Na+ conductance called I ###. ( I### turn on by Repolariza tion )
Pha se 0 : Up stroke of action potential cause by | inward Ca++ flow ( it d erive mem potential toward Ca++ equilibrium potential )
Pha se 3 : Repolarization (caused by | outward K+ conduc tance)

* Phase 4 account for the pace maker activity of the SA node automaticity
( Note -- Phase 1 & 2 are not present in SA nod e ac tion potent ial )

C ond uc tion ve loc ity is the time required for exitation to spread in the heart it is fastest in purkinji system and slowest in
AV node (this is the reason EKG shows PR interval). Conduction velocity depend upon size of inward current during
up stroke.

EXITABILITY is ability of heart to initiate action potential response to inward current, during the course of action
potential changes are describe as Re fra c tory Pe riod .
1. Ab solute Re fra c tory pe riod : Begins with Action potential & end after Pleateau. AP cannot be elicited during this
period.
2. Effe c tive Re fra c tory p e riod : Slightly longer than ARP, conducted action potential can not be elicited.
3. Re la tive Re fra c tory p e riod : Period followed by ARP when repolarization is almost complete. AP can be elicited but
more than usual current is required.
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AUTO NOM IC EFFECT O N HR & C O NDUC TIO N VELOC ITY :
* C hronotrop ic Effe c t : is | or + of HR by | or + firing of the SA nod e .
* Dromotrop ic Effe c t : is | or + of conduction velocity by slowing or speeding the conduction through AV node .
* The Atria, SA node, and AV node have parasympathetic innervation but ventricle do not.
* - ve c hronotrop ic e ffe c t + the HR by + the ra te of Pha se 4 d e p ola riza tion, the mech is + in I ### (+in Na+ c onduc tance).
* - ve d romotrop ic e ffe c t + the conduction velocity through AV node | PR inte rva l.
* Sympathetic innervation is through out the heart.
* + ve c hronotrop ic e ffe c t | the HR by | ra te of Pha se 4 d e p ola riza tion, the mech is | in I ### ( | in Na+ conduc tance ).
* + ve d romotrop ic e ffe c t | the conduction velocity through AV node + in PR inte rva l. (Ventricle filling ma y b e
compromised).
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M YO C ARDIAL C ELL STRUC TURE :
* Sarcomeres is the contractile unit of myocardial cell it runs Z to Z. contain thick filament (myosin) & thin filament
(actin, troponin, tropomyosin)
* Intercalated disc present at Z and maintain cell to cell cohesion.
* Gap Junction present at intercalated disc, and are low resistance pathway b/ w cells. (ac count for elec trica l sync ytium)
* Ttubules continuous with cell mem ( it carries ac tion potential ) well develop in ventricle and poorly develop In atria.
* The magnitude of tension develop in heart is proportional to the | in IC Ca++. ( | IC Ca++ Ca++ triggered Ca++
release from SR )
24

* Ca++ binds Troponin C to remove inhibition of actin - myosin interaction by troponin - tropomyosin to cause
contraction.
* Relaxation occur when Ca++ is reaccumulated in SR by active Ca++ ATPase pump.
-----------------------------------------------------------------------------------------------

C O NTRAC TILITY ( Inotrop ism ) : Is ability of cardiac muscle to develop force at given muscle length.
* It Can be measured by Ejection Fraction ( stroke vol / end diastolic vol ) which is normally 0.55 (55%).
* Fa c tor tha t + C ontra c tility are Parasympathetic by + C a ++ e ntry into the c e ll ( - ve inotrop ic e ffe c t )

* Fa c tor tha t | C ontra c tility ( + ve inotrop ic e ffe c t ) :
1. | HR (In +ve Stair case or Bowditc h Stair case | in IC Ca++ occur over several b ea ts & in Post extra systolic potentia tion IC Ca++ | due to
a ccumula tion )
2. Sympathetic stimulation. via | Ca++ entry during p lateau O R via | Ca++ pump ac tivity in SR ( phosphola mbam )
3. Cardiac Glycoside ( Digitalis, Quabain ). ( digitalis Na+ - K+ ATPase IC Na+ to | Inhibition of Na+ Ca++ exc hange | IC Ca++ )
Eventually all three | the IC Ca++ | contractility .

LENG TH TENSION RELATIO NSHIP :
* It describes the effect of ventricular cell length on the strength of contraction (similar in skeletal muscle).
* Pre loa d is equivalent to End Dia stolic Vol ( | end diastolic vol | in fiber length | in d eveloped tension )
* Afte rloa d is equivalent to Aortic Pre ssure . It | by | Aortic P. ( Velocity of contra c tion + b y | in after load )
Fig :

FRANK SRATLING RELATIO N SHIP : Is based on le ng th te nsion re la tion ship .
* Frank starling relation ship describes | in Cardiac output (stroke Vol) that occur in response to an | in venous P (end
diastolic Vol ).
In other word it is a mechanism that matches Cardiac output and venous return.
* Change in contractility shift Frank starling curve.
Fig:

VENTRIC ULAR PRESSURE - VO L LO O P :
* A cycle of ventricular contraction, ejection, relaxation, and refilling can be seen by combining of two curve into
Pressure - Vol loop . It is constructed by Diastolic and systolic Pressure curve.
Fig:

25

C ARDIAC AND VASC ULAR FUNC TIONAL CURVE :
* Change in End diastolic is major mechanism of alteration in cardiac output.
* Cardiac functional curve shows frank starling relation ship for the ventricle.
* Venous return & vascular functional curve shows relation ship b/ w flow through the vascular sys & the right atrial P.
* Mean systemic P is equal right atrial P when there is no flow in CVS. It | or + by | or + in blood Vol.
* Slope of the venous return curve is determined by resistance of the vasculature.
* A clock wise relationship of venous return curve indicate + in TPR which results into | venous return and cardiac
output. Whereas counter clock wise relationship indicate | TPR | venous return & cardiac output.
| TPR + ve nous re turn to he a rt vs. + TPR | ve nous re turn to he a rt.
* When two curve intersects each other the point is called equilibrium or steady point.
* Equilibrium occur when cardiac output equals venous return.
* + Inotropic agent (digitalis) cause | in contractility | in cardiac output which furthe r lowe rs rig ht a tria l P .
( this is exactly opposite of - ve Inotropic drug )
* | or + in Blood Vol | or + in venous return and cardiac output. It shows shift of curve.
Fig:

C ARDIAC O2 C O NSUMPTIO N : | by | afterload ,| size of heart, | contractility, | HR, ( rememb er after loa d is | by | aortic P)
C a rd ia c outp ut = stroke Vol HR (can also b e measured by Flick's principle C O = O 2 c onsump tion / [O 2] p ulmona ry ve in - [O 2] p ul a rte ry)
Stroke Work = Stroke Vol Aortic P
* Stroke work is work done by heart and fatty acid is primary source of energy for stroke work.

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REG ULATIO N O F ARTERIAL PRESSURE :
* FAST--- Neurally mediated, Baro receptor (stretch rec ep tor) respond fast and regulate minute to minute arterial BP.
* SLOW --- Renin angiotensin and Aldosterone respond slow.
* Baro receptor mechanism present in carotid sinus located near bifurcation of common carotid artery respond to
high or low BP. Additional baro receptor present in Aortic arch which respond only to | in arterial P. (but not to + BP)
* Baro receptor | the firing rate of carotid sinus nerve IX (glossopharyngea l) which carries information to vasomotor
center in brain.
* Set point for the mean arterial P in vasomotor center is 100 mmHg so if set point |, vasomotor center reduce it by |
parasym vagal out flow to heart and + sympathetic out flow to the heart and blood vessels (+ vasoconstriction).
* + Renal perfusion P Renin release Renin catalyze angiotensinogen to angiotensin I (in plasma) than
angiotensin I is converted to ATII (in lung) by ACE.
* AT II vasoconstriction of arterioles (|TPR) & stimulates Aldosterone secretion. (|K+ & + b lood vol also stimula te Aldosterone
secretion )
* Aldosterone Reabsorption of salt and water by distal tubules | blood Vol and mean arterial P.

O THER REG ULATIO N O F ARTERIAL BLO O D PRESSURE :
1. C e re b ra l Isc he mia - - | both parasympathetic & sympathetic outflow. (tha t is why is very hard to control BP in CVA or strokes)
Mean arterial P | to life threatening level.
Flow to other organ (eg kidney) significantly reduced | Renin, | ATII | TPR.
* C ushing re a c tion - - | in IC Pressure compression of cerebral blood vessel cerebral ischemia | sympathetic
out flow | contractility, | TPR with simultaneous reduction in Heart rate (Parasym).
2. C he more c e p tor in a ortic a nd c a rotid b od ie s are very sensitive to hypoxia (because of very high ra te of O2 consump tion)
stimulate vasomotor center to restore BP.
26

3. Va sop re ssin ( ADH) release in response to + blood Vol or P.
ADH a c t on --- V1 re c e p tors cause vasoconstriction (| TPR)
V2 re c e p tors | reabsorption of water by distal tubule and collecting duct.
4. Atria l na triure tic Pa ptide ( ANP) release in response to | atrial P dilation of arterioles (inhibit vasoconstric tion), & + TPR. It
also | salt & water excretion and inhibit Renin release.

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* Flow through capillaries is regulated by contraction and relaxation of the arterioles and the precapillaries sphincters.
Remember capillaries do not have smooth muscles instead containing endothelial cells.
* BBB is a tight cleft b/ w endothelial cells of capillaries. In intestine & liver these cell clefts are wide open called
Sinosoid s it allow protein to cross. ( 3 types of subs cross capillary wall 1. lipid soluble subs. 2. sma ll water soluble subs. 3. large wa ter
soluble subs via pinocytosis. )

FLUID EXCHANG E AC ROSS C APILLARIES :
* It can be determined by Starling equation Jv = K] [ ( Pc - Pi ) - ( tc - ti ) ] Jv is fluid flow and Kf is filtra tion coefficient
Pc (Capillaries hydrosta tic P) when | it cause net filtration. Pc is hig he r a t a rte riola r e nd of the capillaries than venous end.
Exc e pt in glomerular capillaries where it is nearly constant. ( Rememb er | arteriolar or venous P | Pc but | venous P has grea ter
effec t on Pc )
Pi ( Interstitia l fluid hydrosta tic P) Normal Pi is 0mmHg . | in Pi oppose filtration out of the capillaries.
tc ( Capillaries oncotic or colloid osmotic P) when | opposes filtration out of capillaries.
ti ( Interstitia l oncotic or colloid osmotic P) when | favor filtration out of capillaries.
Fa c tor tha t inc re a se filtra tion a re | Pc, +Pi. +tc, |ti .

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FUNCTIO N O F LYMPHNO DE:
* Excess filtered fluid is returned to circulation via lymph. One way flap valve permit unidirectional lymph flow.
Skeletal muscle contraction also aid it.
* Edema caused by excess filtration or blocked lymphatics or by | Pc, + tc, | K]. (K] | due to burn & inflamma tion)
* EDRF (produce by endothelial c ell) relaxes smooth muscle by Guanylate cyclase mech produce GMP. ( one form of EDRF is
Nitricoxide )
* Ach vasodialation by stimulation of EDRF production.
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SPEC IAL C IRC ULATIO N :Blood flow is regula ted by a ltering arteriolar resista nc e, can b e varied depends upon metabolic need.
Autoc irc ula tion - - When perfusion P | arteriolar smooth musc le stretc hes follow by contrac tion vasoconstric tion oc c ur (by this maintain
constant flow)
Ac tive Hype re mia - - Is blood flow to organ proportiona l to its metabolic need . eg . Heart
Re a c tive Hyp e re mia - - Is | in blood flow to an organ after a period of oc clusion to flow. eg . Heart
Va sod ila tor me ta b olite s are CO2, H+, K+, lactate and Adenosine.
-------------------------------------------------------------------

VASO ACTIVE HO RM ONES :
* Hista mine arteriolar dilation & venoconstriction. It | Pc & cause local edema. (Wheal is an ed ema results from local
hista mine release).
* Bra d ykinine arteriolar dilation and venous constriction it also cause edema.
* Se rotinin arteriolar vasoconstriction. It release upon vessel damage and prevent blood loss.
* Prosta g la nd ins --- PGI2 (prostac yc lin) and PGE vasodilation
PGF va soc onstric tion
TxA2 va soc onstric tion

C O RO NARY ARTERY C IRCULATIO N : 5% is resting cardiac output.
* Control by local metabolites specially hypoxia and Adenosine vasodilatation to | blood flow.
27

* Exhibit Autoregulation, active and reactive hyperemia.
* During systole mechanical compression of the coronary vessel reduces blood flow, Reactive hyperemia occurs after
that brief period of occlusion to replay the O2 dept. (Mechanical Effect)
* Sympathetic nerev play a minor role.

C EREBRAL CIRC ULATIO N : Is 15 % of resting cardiac out put.
* Control by local metabolites specially CO2 or of pH vasodilatation of cerebral arteries to | blood flow.
* Vasoactive subs in general circulation have little or no effect on cerebral circulation because of BBB.

SKELETAL M USC LE C IRC ULATIO N : Is 20 % of resting cardiac out put.
* At rest symp control of blood flow predominate where as during exersize local metabolites control over rides
sympathetic control.
* Local metabolites like lactate, Adenosine, K+, dilates vessel and increase blood flow.
* Mechanical effects compensate by reactive hyperemia. (due to temporary compression of arterioles with resultant
vasodilata tion )
* o receptors cause vasoconstriction where as | receptors cause vasodialation.

SKIN C IRC ULATIO N : Is 5 % of resting cardiac output.
* Skin have extensive sympathetic innervation and flow of blood is in extrinsic control (temperature regulation).

PULM O NARY CIRC ULATIO N : Is 100% of cardiac out put. Local metabolites are most imp mechanism.

RENAL C IRC ULATIO N : Is 25% of resting cardiac out put.
-----------------------------------------------------------------

* Upon Standing (gravity) | in venous P, | Pc | Filtra tion initial + in stroke vol & cardiac output comp ensa tory mec h starts (via carotid
baro rec ep tors) HR |, TPR | BP return to norma l BP.
* On Exercising HR |, stroke vol |, cardiac output |, Arterial P | (slightly), Pulse P | (due to | stroke vol), TPR + (due to vasodilata tion of skeletal m
bed), Arterio venous O2 differenc e | ( due to increase O2 consump tion).
* On Hemorrhage HR |, TPR ,| contrac tility |, unstressed vol + (stress vol |), Renin |, ATII |, Aldosterone |, EN & norEN |, ADH |. ( Rememb er
vaso constric tion occ ur in skeleta l, splanchnic & cuta neous vascular b ed; but it does not oc cur in coronary and cerebral va scular b ed because
to ensure maintained blood flow to heart and brain ).
----------------------------------------------------------------------------------

* Blip is aortic P tracing occur following closure of aortic valve also called dicrotic notch or Incisura.
* Rapid flow of blood from atria to ventricle cause 3rd heart sound (normal in c hildren but associated with dis in adults).
* Inspiration split the second heart sound.
* Ventricle filling is divided into Rapid ventricle filling & Reduced ventricle filling (Diastasis) which is last part of ventricle
filling curve.

NEURO PHYSIO LO G Y
* Autonomic nervous sys (symp, parasymp & enteric) is distinct from Somatic nervous sys which innervate skeletal muscles
and use ACh as a NTwhere as receptor is nicotinic.
* Symp neurotransmitter is norEN in effector organ except in sweat glands where it is ACh and receptors are
muscarinic.
* Parasym and Symp receptors in ganglion are Nicotinic and NTis ACh.
* Symp ganglia are located in paravertebral chain where as parasymp ganglia are located in effector organ.
* Preganglionic symp fiber are short and synapse in autonomic (paravertebra l) ganglia its cell bodies are present in CNS
& Postganglionic symp fibers are long & synapse in effector organ & its cell bodies are located in Autonomic
(paravertebral) ganglia.
* Preganglionic parasymp fibers are long and synapse in autonomic ganglion in effector organ it cell bodies are
present in CNS & postganglionic parasym fibers are short & synapse on effector organ, its cell bodies are present in
autonomic ganglion.
* Parasymp receptor in effector organ is Muscarinic but in skeletal muscle (somatic) is Nicotinic.
* Adrenal medulla is a special case in which preganglionic fiber syna p se d ire c tly on c hroma ffin c e lls of adrenal
medulla it use ACh as NT& secret EN 80% & norEN 20% . (because rememb er preganglionic fibers norma lly synapse on ganglion).
28

ADRENERG IC RECEPTO R TYPES :
1. o1 - located on smooth muscle except bronchial smooth muscle Exc ita tion ( via IP3 me c h) & is equally sensitive to
EN & norEN.
2. o2 - located on smooth muscles, Presynaptic nerve terminal, platelets and fat cells Inhib ition ( via c AM P ma c h) .
3. |1 - located in heart, kidney and fat cells Exc ita tion ( via c AM P ma c h) .
4. |2 - located on vascular, bronchial and GI smooth muscles Re la xa tion ( via c AM P ma c h) and is more sensitive to EN
than norEN and more sensitive to EN than o receptors.
* When sma ll a mount of EN release from adrenal medulla cause vasodilation but when large a mount of EN release from adrenal medulla for eg as
in pheochromocytoma results into vasoconstric tion (via o rec ep tors).

* o1 --- constrict pupil. whe re a s |1 --- heart contraction, | renin secretion, and lipolysis in fat cells.
* In sweat gland sympathetic action | sweating but neurotransmitter is ACh and receptors are muscarinic.

C HO LINERG IC RECEPTO R TYPE :
1. Nic otnic re c e p tors (ac tivated by ACh or Nicotine) are located in autonomic ganglia & neuromuscular junction
Excitation ( nic otinic or Ac h re c e p tors a re ion c ha nne l for Na + a nd K+ ) . Ganglion blockers ( He xa m e thonium , Trime thp p ha n ) block
nicotinic receptor for Ach in autonomic ganglia but not at neuromuscular junction ( b e c a use re c e p tors a re not id e ntic a l) .
2. M usc ura nic re c e p tors located on
* In Heart M2 receptors are located on SA node Inhibition ( via c AM P) by + the rate of spontaneous depolarization.
* In Glands Exitation ( via IP3)
* In Smooth muscle Excitation ( via IP3) with resultant constriction of bronchial smooth muscle, contract bladder wall
& relax sphincter, | GI motility and relax sphincter. ( note : in va sc ula r smo oth musc le M re c e p tors c a use re la xa tion or va sod ila tion)
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SENSO RY SYSTEM :
A. Typ e of se nsory tra nsd uc e r :
1. Mechano Receptors -- * Pacinian Corpuscles (encod e vibration and tapping) & adop t rapidly
* Meissners corpuscles present on non hairy skin (encod e velocity) & adopt rapidly
* Merkels disc ( loca tion ) & adop t slowly * Ruffini,s corpuscles (encode pressure) & adopt slowly
* Joints, stretch rec ep tors in muscles * Hair cell in auditory and vestibular system.
2. Photo Receptors ------------- Rods and Cones of the retina.
3. Chemo Receptors ----------- Olfactory Receptors, taste receptors, osmo receptors and Carotid body Receptors.
4. Temp & Pain Receptors ---- Noci Receptors.
(Pacinian vibrates meissners run (velocity) to merkel loca tion and shares ruffini's pressure)

B. Fib e r type a nd ve loc ity :
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
G e ne ra l Fib e r Typ e Se nsory Fib e r Typ e Dia m e te r C ond uc tion Ve lo c ity
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
A - Alp ha (large o motoneuron) Extrafusal fiber I a (musc le spindle afferent) Largest Fastest
I b (golgi tendon organ) Largest Fastest
A - Beta ( Touch & Pressure) II Sec Afferent of musc le spindle touch & pressure Medium Medium
A - Ga mma ( motoneuron to musc le spindle) Intrafusal fiber Medium Medium
A - Delta (touch, pressure, temp, pain) III Touch, Pressure, Temp & Fast Pain Sma ll Medium
B Preganglionic Autonomic Fiber Sma ll Medium
C Slow Pain, Postga nglionic Autonomic Fiber IV Pain, Temp (unmyelina ted) Smallest Slowest
--------------------------------------------------------------------------------------------------------------------------------------------------------------------------
* Receptive Field in the region that contain sensory transducer can be excitatory or inhibitory.

STEP IN SENSO RY TRANSDUCTIO N : Stimulus arrives in sensory receptors opening of ion channel in sensory receptor
inward current cause depolarization ( except in photo receptors where light cause hyper polarization).
* Action potential is fired only when stimulus to receptor potential is large enough to exceed threshold.

ADO PTATIO N O F SENSO RY RECEPTO R :
1. Slow adopting receptor eg. musc le sp ind le , p re ssure , slow p a in. Respond relatively to prolong stimulus.
2. Rapidly adopting receptor eg. p a c inia n c orp usc le s, lig ht touc h respond fast but show decline in action potential
frequency with time in response to constant stimulus.
29

SENSO RY PATHWAY :
a. 1
st
order neuron --- Primary afferent neuron receive signals. These cell bodies are located in dorsal root ganglia and
CN ganglia.
b. 2
nd
order neuron --- Located in spinal cord & brain stem. Receive information from primary afferent neuron & send
it to thalamus.
c. 3
rd
order neuron --- Located in sensory nucleus of thalamus from here it send information to cerebral cortex.
d. 4
t h
order neuron --- Located in cortex and result in conscious perception of stimulus.
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PATHWAY O F SO MATO SENSO RY SYSTEM :
1. Dorsa l C olumn Syste m: * Consist of group II fiber which run in the Dorsal Root; it asc end ipsila terally to the Nuc Gra cilis & Cunea tus of
(Posterior column sys) medulla from here 2
nd
ord er neuron cross the mid line and ascend to the contrala teral thala mus.
* Dorsal column system process sensa tion of touc h, p re ssure , vib ra tion, a nd mo ve me nt.
2. Ante rola te ra l Syste m: * Consist of group III and IV fibers which enter the spinal cord and termina te in the dorsal horn. Form here 2nd ord er
neuron sensory projec t across the midline to the Anterola teral quadrant & asc end to the contra la tera l thala mus.
* Anterola teral system proc ess sensa tion of te mp a nd p a in.

* Destruction of thalamic nuclei result in loss of sensation on the contra lateral side of the body.

SO M ATO SENSO RY C O RTEX :- * Major somatosensory area of cortex is S I and S II. S I have somatotropic representation
similar to thalamus. This map of body is called Homunculus (HAL).
PAIN: * Perceive by Noci receptors which are free nerve ending and neurotransmitter is Substance P (opiate inhibit it).
* Fa st p a in fib e rs are g roup III fib e rs shows rapid onset and offset and is loc a lize d .
* Slow p a in fibe rs are C, ( IV) fib e rs perceive aching, burnig, throbbing sensation and is poorly loc a lize d .
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VISIO N :
* Refractory power of lens is measured by Diopters. 10 Diopters = 10 cm
* Emme trop ia -- Normal -- light focus on retina.
* Hyp e rop ia - - Farsightedness -- Light focus behind the retina (convex lens).
* M yop ia - - Nearsightedness -- Light focus in front of retina (Biconcave lens).
* Astig ma tism -- Curvature of lens is not uniform (cylindrical lens).
* Pre sb yop ia - - Loss of accomodation of lens with aging. The near point appear more farther from eye (convex lens).

* Receptor cells are Rod and Cones which are not present at Optic disc and create a blind spot.
* Fe w c one s syna p se on sing le Bip ola r C e ll whic h further synap se on single Ganglion Cell this arrangement cause hig h a c uity & lo w se nsitivity.
* M a ny Rod s syna p se on sing le b ip ola r c e ll which results into le ss a c uity & g re a te r se nsitivity . (because many rods can ac tiva te single bipolar c ell).
* In FOVEA where acuity is high Cone Bipolar ratio is 1:1 .
* Horizontal and Amacrine Cell form local circuit with Bipolar Cell.
* Axon of the Ganglion form Optic Nerve & Optic Tract terminate in the Lateral Geniculate Body of the thalamus.
* Fiber from Lateral Geniculate Body form Geniculocalcarine Tract and pass to cortex of Occipital lobe.
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FUNC TIO N RO DS C O NES
-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Se nsitivity to lig ht Sensitive to low intensity to light ( Night vision ) Sensitive to high intensity light ( Day vision )
Ac uity Low visual ac uity ( not present in FOVEA ) High visual Acuity ( Present in FOVEA )
Da rk Ad a p ta tion Rod adopt la ter Cones adop t first
C olor vision NO NO
M ore a t p e rip he ra l of re tina YES YES
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* Cutting the Optic nerve Blindness of ipsilateral eye.
* Cutting the Optic chiasm Hetronymous Bitemporal Hemianopsia.
* Cutting the Optic Tract Homonymous Contralateral Hemianopsia.
* Cutting the Geniculocalcarine Tract Homonymous Hemianopsia with Macular sparing.
* Cutting unilateral temporal lobe radiation Homonymous Quadrantopia (pie in the sky)
* Bilateral visual cortex lesion Macular sparing.

30

Photo Re c e p tion of Rod s:
* In Rod Photosensitive element is Rhodopsin composed of Scotopsin & Retinine ( Aldehyd e of vit A ) . Vit A deficiency
cause night blindness. (because Vit A is essentia l for regenera tion of Rhodopsin).
* Lig ht on re tina c onve rt 11- c is Rod op sin All tra nsRod op sin M e ta Rod op sin I I ( a c tive form) tha n M e ta rod op sin II a c tiva te s G p rote in c a lle d
Tra nsd uc in whic h in turn a c tiva te Phosp hod ie ste ra se Phosp hod ie stra se furthe r c a ta ly ze c onve rsion o f c G M P into 5 G M P ( c G M P le ve l +) . Tha n
+ c G M P re sults into c losure of Na + c ha nne l & Hyp e rp ola riza tio n of the c e ll M e mb ra ne . ( | lig ht c a use | d e g re e of hyp e rp ola riza tion ) .
* Excitatory NThyperpolarize bipolar & horizontal cell in response to light. vs.
Inhibitory NTdepolarize it in response to light.

Re c e ptive visua l Fie ld :
* Light hit the centre of receptive field & depolarize (excite) the Ganglion cells & constitute On Center Off Surround
receptive visual field pattern. (On Center Off surround is another possible pattern in which light hits the surround of
receptive field & hyperpolarize (inhibit) the ganglion cell)
* Lat Geniculate Cell of the Thalamus retained the Center - Surround ON - OFF pattern transmitted from Ganglion cell.

REC EPTIVE FIELD O F VISUAL CO RTEX : Detects shape and orientation of figure. Visual Cortex comprise of three Layers.
1. Simple Cells (have c enter -surround On - Off pa ttern & are elonga ted Rods) --- Respond to Bars of light with correct position &
Orientation.
2. Complex Cells --- Respond best to moving Bars and edge of light.
3. Hyper Complex Cells --- Respond best to lines with Particular Length and to curve and angles.
--------------------------------------------------------------------------------------------------------------------

AUDITO N :
* Frequency measure in Hertz where as Intensity in Decibles.
Fig:

* Middle ear is air filled where as inner ear is fluid filled.
* M id d le e a r contain Tympanic mem, Ossic les (malleus, incus, stapes) and Oval window where as Inne r e a r consist of Bony lab yrinth (semicirc ular
canal,
cochlea, vestibule) and series of Duc ts called Membranous labyrinth whic h contain endolymp h (inside the duc t) and perilymph (out sid e the
duc t).
* Sound c a use Tymp a nic me m to vib ra te , in turn Ossic le vib ra te a nd p ushe s the sta p e s in to the Ova l Wind ow ( a
me m
b / w inne r e a r a nd midd le e a r ) whic h d isp la c e s the fluid in the inne r e a r.
* Sound energy is amplified by lever action of Ossicles and send conc of sound wave from Tympanic mem to Oval
Window.

C O CHLEA consist of three Tubular canals.
1. Scala Vestibuli --- Contain perilymph and is | in Na+.
2. Scala Tympani --- Contain Perilymph and is | in Na+.
3. Scala Media --- Contain endolymph and is | in K+* ( Scala Media is Bordered b y Basilar Mem the site of Organ of Corti ).

Fig:

31

O RG AN O F C O RTI is located on Basilar mem. Its Receptors are inner Hair cells (in single row) & outer Hair cells (in parallel
row) Outer Hair cells are greater in number than inner Hair cells.
* Cilia protrudes from Hair cells and imbedded into Tectorial mem .
* Spiral Ganglion contain cell bodies of CN VIII which synapse on Hair cells.
* Sound wave vibrates Organ of Corti Basilar mem to vibrate & push against Tectorial mem Hair cells to bend
bending of cilia (which cause change in K+ conduc ta nc e) Depolarization Ossillating potential results. (bending in other
direc tion cause hyp erpolarization)
* Ossillating Potential (Cochlear microphonic potential) of Hair cell intermittent firing of Choclear nerve.

ENC O DING O F SOUND WAVE :
* Base of the Basilar mem ( near Oval and Round window ) is narrow and stiff it respond best to high Frequency.
* Apex of the Basilar mem ( near Helicotrema ) is wide and compliant it respond best to low Frequency.

C ENTRAL AUDITO RY PATHWAY :
* C oc hle a r ne rve Fib e r a sc e nd throug h La te ra l La minisc us Infe rior C ollic ulus M id d le G e nic ula te nuc le us of tha la mus a ud itory C orte x.
* Fiber may crossed or uncrossed that s why lesion of the chochlea of one ear cause unilateral deafness where as
more central
unilateral lesion does not cause complete unilateral deafness.
* Ability to recognize a patterned sequence is a property of Cerebral Cortex.
* Remember always Medial geniculate to Ear and lateral geniculate to Eye.

VESTIBULAR SYSTEM :
* Vestibular organ is a membranous labyrinth consisting of three perpandicular canal filled with Endolymph.
1. Semicircular canal --- De te c t a ng ula r a c c e le ra tion a nd rota tion.
2. Utricle --- De te c t line a r a c c e le ra tion.
3. Saccule --- Also de te c t Line a r a c c e le ra tion .

* The vestibular receptor cells are Hair cells located at the end of each semicircular canal.
* Vestibular Hair cells are embedded in gelatinous substance called C a p ula .
* Kinoc ilium is a single long cilium where as Ste re oc ilia are small cilium.
* If Sterocilium b ends toward the Kinocilium Hair c ells Depola rize whe re a s If Sterocilium bends away from Kinocilium Hair cells Hyperpolarize.
* During initial counterclockwise rotation Left Horizontal canal is excited & Right Horizontal canal is inhibited but after
few seconds endolymph catches up the movement of head & capula; cilia return to their upright position.(no more
hyperpolariza tion or d epolariza tion)
* When head sud d e nly stop s endolymph continues to move to counterclockwise for a while (cause cilia to move in opp
direc tion) if the hair cell was depolarized with initial movement, it will now hyperpolarized and hyperpolarized one
will depolarize.

* Ve stib ula r - O c c ula r Re fle x :
Nysta g mus --- An initial rotation of head cause eye to move slowly in opposite direction when limit of eye
movement reaches the eye rapidly snap back than move slowly again. (nystagmus in rest arise from disruption in c entra l or
peripheral vesticular connec tion)
Post rota tory nysta g mus --- Occur in the opposite direction of head Rotation.
-----------------------------------------------------------------------------

O LFAC TO RY receptor cells are present on epithelia and are true neurons. It conduct action potential to CNS via CN I.
* These neuron are the only eg. in nervous system that turn over and replace neuron.
* CN I carries information from receptor cell to Olfactory bulb, the Axon of olfactory nerve is unmyelinated C fiber
and are smallest therefore slowest.
* Olfactory epithelium is a lso inne rva te d b y trig e mina l ne rve V which detect Noxious stimulus such as Amonia.
* Olfactory nerve passes through the Cribriform plate to Olfactory bulb, its fracture Hypoosmia, Anosmia.( CN V
response is inta c t )
* Mitral cells in the Olfactory bulb are 2
nd
order neurons from Olfactory Tract and project to Prepiriform Cortex.
* Odorant molecules bind to the olfactory receptor neuron activate G protein activates adenylate cyclase |
cAMP Open Na+ channel depolarization of receptor potential Fire action potential.
32

TASTE :
* Taste buds are located on special Papillae & are covered with micro villi. ( taste rec ep tors are present on taste bud )
* Ant 2/ 3 of tongue has Fungiform Papillae detect salty and sweety sensation and is innervated by Facial nerve VII.
* Post 1/ 3 has Circum vallate & Folliate papillae detect sour & bitter sensation & is innervated by Glossopharyngeal
nerve IX.
* Back of throat and Epiglottis is innervated by vagus nerve X.
* CN VII, IX, X enter the medulla ascend in solitary tract where 2
nd
order neuron terminates in solitary nucleus; from
here itproject primarily ipsilaterally to ventral posteromedial nuc of thalamus taste cortex (which is present in the ventra l
region of Post central gyrus).
--------------------------------------------------------------------------
M O TO R SYSTEM :-
* Motor unit is a single motoneuron plus muscle fiber that it innervates. (single motoneuron may innervate few musc le for fine
movement & many musc le for large movement) .
* Motone uron p ool is a group of neuron that innervates fibers with in same muscle.
* Force muscle contraction is graded by recruitment of additional motor unit ( size p rinc ip le ) .
* Sma ll motone uron -- innervate few muscle fibers, has lowe r thre shold therefore fire first and generate small force.
* La rg e motone uron -- innervate many muscle fibers, has hig he st thre shold and therefore fire last and generate large
force.
-------------------------------------------------------------------------
M USC LE SENSO RS :- 4 Types of muscle sensors
1. Muscle spindle Ia has parallel arrangement with extrafusal muscle fiber, detect both static & dynamic changes in
muscle
length.
2. Golgi tendon organ Ib has serial arrangement with extrafusal muscle fiber detect muscle tension.
3. Pacinian Corpuscles II detect vibration.
4. Free nerve ending III, IV detect noxious stimuli.
TYPE O F M USC LE FIBER :-
1. Extra fusa l fibe r -- make muscle bulk and stimulate by o motoneuron. It p rovid e forc e of muscle contraction.
2. Intra fusa l fib e r -- are smaller than extrafusal fiber. It e nc a p sula te d to form musc le sp ind le & run parallel to extrafusal
fiber but do not run entire muscle length.

Intrafusal Fiber
.\
Ia typ e afferent musc le strength (d yna mic c ha ng e s) Nuc b a g fib e r Nuc c ha in fib e r musc le c hange (sta tic c ha ng e ) II type a fferent

-------------------------------------------------------------------------
* Muscle spindle -- Finer movement need greater no of muscle spindle in muscle. (muscle spindle consist of intra & extra fusal
muscle fiber)
* There are two type of intrafusal fiber present in muscle spindle.
1. Nuc le a r Ba g fib e r: Detect Dyna mic c ha ng e s (rate & change in musc le strength a t motion) & is Innervated by Ia a ffe re nt.
2. Nuc le a r C ha in fib e r: Detect Sta tic c ha ng e (a t rest) in the muscle length & is innervated by group II a ffe re nt.

FUNCTIO N O F MUSC LE SPINDLE : Muscle spindle opposes over stretching of muscle by contracting it.
* Stretched muscle further stretches Muscle spindle Stimulate Ia (velocity) & group II (static) afferent fibers
stimulate o motoneuron in spinalcord contraction.
Func tion of Motone uron :- Motoneuron Innervate intrafusal muscle fiber it adjust the sensitivity of muscle spindle. o
& motoneuron are coactivated so muscle spindle remain sensitive to change in muscle length during contraction.

M USC LE REFLEXES
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
REFLEX NO O F SYNAPSE STIM ULUS AFFERENT FIBER RESPO NSE
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Stretc h Reflex ( Knee Jerk ) Monosynsp tic Stretch Musc les Ia Muscle contra c tion
Golgi Tendon Reflex ( Clasp Knife ) Disynaptic Contra c t musc le Ib Musc le Relaxa tion
Flexion withdrawal Reflex Polysynap tic Pain II, III, IV Ipsila tera l Flexion & contrala teral
( after touching Hot objec t ) Extension
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
33

Stre tc h Re fle x -- Ia afferent synapse on o motoneuron to cause contraction in the muscle that was stretched.
( | motor a c tivity | the sensitivity of muscle spindle whic h result into exaggera ted stretch reflex ).
G olg i te nd on Re fle x - - Activated muscle contraction stimulate Ib afferent fiber of Golgi tendon than Ib inhibit
interneuron in spinal cord which further inhibit o motoneuron Relaxation of muscle that was
originally contracted.
C la sp Knife re fle x is an exaggerated form of the Golgi tendon ref it can occur in Corticospinal tract dis ( sp a stic ity ) .
Fle xion withd ra wa l re fle x -- After touching a hot object pain stimulus from II, III, and IV afferent fiber cause ipsilateral
Flexion and contralateral extension ( c ross e xte nsion re fle x ) to maintain balance. After
discharge does not allow the muscle to relax for some time because of persistent neuronal
activity in polysynaptic circuit.
---------------------------------------------------------------

SPINAL O RG ANIZATIO N O F M O TO R SYSTEM :
1. C onve rg e nc e is when more than one muscle spindle stimulates single motoneuron ( Ia afferent ) produce sp a tia l
Summa tion ( more tha n one input bring musc le to threshold ) & te mpora l summa tion ( input arrive rapid succ ession ).
2. Dive rge nc e is when Ia afferent (muscle spind le) project to more than one or all motoneuron of the homonymous mus.
3. Re c urre nt inhib ition ( Re nsha w c e lls) : Renshaw cells are inhib itory ne uron it inhibit motoneuron (- ve feed back ) in
ventral horn of spinalcord. It receives input from collateral axons of motoneuron.
---------------------------------------------------------------

BRAIN STEM C O NTRO L O F PO STURE : Motor center and Pathway are of two types,
1. Pyra mid a l Tra c t -- is Corticospinal & Corticobulbar Tract. Both Pass through medullary pyramids.
2. Extra p yra mid a l Tra c t -- are all other pathway.
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

EXTRAPYRAM IDAL TRACTS AND ITS O RIG INS :
1. Rub ro sp ina l Tra c t - - Origina te in re d nuc & projec t interneuron to la tera l spinalcord. It stimula te fle xors & inhib it e xte nsor.
2. La te ra l Ve stib ulosp ina l Tra c t -- Origina te in Die te rs nuc & projec t to Ipsila tera l motoneuron & interneuron. It stimula te e xte nsors & inhib it fle xors.
3. Pontine Re tic ulosp ina l Tra c t -- Origina te in nuc in p ons & projec t to Ventromedial spinalcord. It stimula te b oth e xte nsors & fle xors.(but more Ext)
4. M e d ulla ry re tic ulosp ina l Tra c t -- Origina te in me d ulla ry Re tic ula r forma tion & projec t to spinalcord. It inhib it b oth e xte nsor & fle xor. (b ut more ext)
5. Ta c tosp ina l Tra c t -- Origina te in sup e rior c ollic ulus & projec t t o cervical spinal cord. It c ontrol ne c k musc le s.
EFFECT O F TRANSECTIO N O F SPINAL C O RD :
1. Pa ra p le g ia (Loss of voluntary movement) below the level of lesion.
2. Loss of c onsc ious se nsa tion below the level of lesion.
3. Initia l loss of re fle xe s (spinal shock) flaccidity occur below the level of lesion due to loss of o & motoneuron.
( with time partial recovery and return of reflexes or even hyperreflexia will occ ur )

* C7 le sion results into loss of sympathetic tone to the heart + HR & + BP .
* C3 le sion will stops breathing because respiratory muscle disconnected from brain stem Control center.
* C1 le sion cause Sudden death eg. as in hanging.

EFFECT O F TRANSECTIO N ABO VE THE SPINAL C O RD :
* Le sion a b ove La te ra l Ve stib ula r Nuc le us - - remove inhibition from higher center and cause excitation of o and
Motoneuron De c e re b ra te rig id ity (rigid posture).
* Le sion a b ove Pontine Re tic ula r forma tion - - removal of inhibition from pontine reticular formation & resultant
excitation of o & motoneuron & cause De c e re b ra te rig idity (rigid posture)
* Le sion a b ove the Re d Nuc le us results in De c ortic a te Posturing and inta c t tonic ne c k re fle x.
-----------------------------------------------------------------------

C EREBELLUM :- Central control of movement.
FUNCTIONS --- 1. Control of Balance an eye movement conduct by Ve stib ulo Ce re be llum.
2. Planning and Iniciation of movement control by Ponto C e re b e llum.
3. Synergy (Control of ra te, Forc e, Range and Direc tion of movement) control by Sp ino Ce re b e llum.

34

La ye rs of c e re be lla r c orte x :
1. G ra nula r La ye r ( inner most ) -- contain granule c ells, Golgi II cells & Glomeruli. ( In glomeruli axons of mossy fibers form syna pse on granular &
golgi II cells ).
2. Pe rkinji C e ll La ye r ( middle layer ) -- out p ut is a lwa ys inhib itory.
3. M ole c ula r La y e r ( outer la yer ) -- contain Stella te & Basket c ells, Dendrites of perkinji & golgi type II c ells & parallel fib ers (axons of granule cells).

C onne c tion of Ce re b e lla r Corte x :
* Inp ut of c e re b e lla r c orte x :
1. C limb ing Fib e rs - Play role in c e re b ra l motor le a rning . It originate in infe rior O live (medulla) make multiple synapse
on perkinji cells results in c omp le x Sp ike s.
2. M ossy Fibe rs - Originate in brain stem & spinalcord. It synapse on perkinji fibers (via interneuron) & on glomerular
Complex. M ossy fib e r g ive rise to p a ra lle l fib e r e xc ite multip le p e rkinji c e lls a s we ll a s inhib itory ne uron inhib ition.

O ut p ut of c e re be lla r c orte x :
* The only out put from cerebellar cortex are perkinji cells and is always inhibitory (neurotransmitter is GABA)
* Inhibitory out put project to deep cerebellar nuclei and vestibular nuclei. It regulates synergy.

Disord e r of C e re b e llum ( Ata xia ) :
La c k of c oord ina tion: (Poor execution & delayed inhibition of movement), Inability to perform rapid alternating movement
called Dysdiadochokinesia.
Inte nsion tre me r occur during voluntary movement.
Re b ound Phe nome non - inability to stop movement.
------------------------------------------------------------------------

BASAL G ANG LIA :- Control of movement
* Basal ganglia p la n a nd e xe c ute smooth move me nt by modulating thalamic out flow to motor cortex. Many of its
synaptic connection are inhibitory and use GABA. (Its lesion results into loss of GABA)

Ba sa l G a ng lia c onsist of :-
1. G lob us p a llid us Lesion Ina b ility to ma inta in p ostura l sup p ort and a the tosis (involuntary slow movement of hand & foot).
2. Sub Tha la mic Nuc le us Lesion Wild flinging movement called He mib a llismus. (ca used b y release of inhibition on
contra la tera l side)
3. Stra itum Lesion Q uic k c ontinuous unc ontrolla b le move me nt as in Huntington. (caused b y release of inhibition)
4. Puta me n Lesion involuntary purposeless muscular movement called C hore a .
5. Sub sta ntia Ne g ra Lesion Destruction of Dopaminergic neuron O ve r re a c tivity of inhib itory p a thwa y of Stra itum
& Glob us p a llid us Lead pipe rigidity, resting tremor & reduced voluntary movement ( Pa rkinson Dis) .

M O TO R C O RTEX :-
1. Pre motor C orte x & Supp le me nta ry M otor Corte x ( a re a 6 ) generate a p la n for move me nt .
* It is active during Mental Rehearsal for movement which than transfer to primary motor cortex for execution.

2. Prima ry M otor C orte x ( a re a 4 ) is responsible for e xe c ution of move me nt.
* Epileptic event in Primary motor cortex Jacksonian Siezures.
* Homunculus is upside down Representation of the Human Body in cerebral cortex.
--------------------------------------------------------------------------

HIGHER FUNCTIO N O F CEREBRAL C O RTEX :-
1. EEG Find ing s :
* EEG wave consist of alternating excitatory & inhibitory synaptic potential in the pyramidal cell of the cerebral
cortex.
* EEG change occur due to cortical evoked potential. In alert adult | waves predominate & Upon relaxation o
waves predominate where as during sleep slow waves predominate.

35

2. SLEEP :
* Sleep wake cycle occur in c irc a d ia n rhythm which resides in Sup ra c hia sma tic nuc le us of hypotha la mus, which
receives input from retina.
* Rapid eye movement sleep occur every 90 min. During REM sleep EEG resembles that of awake person. Most
dream occur during REM sleep. | age and Benzodiazepine + in REM sleep.
* Slow wave sleep is Dream less Sleep ( dream do occur but cant be remmember ).

3. LANGUAG E :-
* Left hemisphere is usually dminant with respect to language even in left handed person. Its lesion Aphasia.
* Right hemisphere is more dominant in Facial expression, Intonation (voice tone), Body language, and Spatial task.
* Damage to We rnic ks Are a Se nsory Ap ha sia ( d ifficult to und erstand written and spoken langua ge ) .
* Damage to Broc a Are a M otor Ap ha sia ( In whic h speech and writing are affec ted but understa nding is inta c t ).

4. Short Te rm M e mory: Involve synaptic changes.
5. Long Te rm Me mory: Involve structural changes & is resistant. ( b ila te ra l hip p oc a mp us le sion no more ne w long - te rm me m orie s)
----------------------------------------------------------------------

BBB AND C SF :
* BBB consist of endothelial cells of cerebral capillaries and choroids plexus epithelium.
* Lipid soluble subs like CO2, O2, & H2O cross BBB freely but other subs transport (in & out) by carrier in choroid plexus
epithelium.
* Protein and cholesterol are excluded from CSF because of large molecule size.
* Composition of CSF is same as interstitial cerebral fluid of brain.
FUNCTIO N : * BBB maintain constant enviornment of neuron in CNS and prevent scape of CSF and neurotransmitter.
* Non Ionized ( lipid soluble ) drug absorb more easily than ionized ( non lipid soluble ).
* Inflamation, Radiation, or tumor cell may destroy BBB.

C O MPO SITIO N O F C SF & BLO O D C O NC :
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
C SF ~ BLO O D C SF ( BLO O D C SF ) BLO O D
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Na+ K+ M g ++
Cl- C a ++ C re a tinin
HCO3- G luc ose
O smola rity Cholesterol & protein.
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

TEMP REG ULATIO N :
* Thyroid hormone | metabolic rate heat production ( b y stimula ting Na + - K+ ATPa se ) .
* Cold Te mp Activate sympathetic sys | metabolic rate & heat production ( via | re c e p tors a c tiva tion on b rown fa t)
* Shive ring is most potent heat generating response by Post Hyp otha la mus ( via o & moto ne uron c ontra c tions ) .

HEAT LO SS :
* Heat loss response is also control by Post Hyp otha la mus.
* | Temp + sympathetic tone to the skin and blood vessels shunting the warm blood near the surface of the
skin | heat loss by radiation and convection.
* Heat can also loss by evaporation via sweat glands activity which is under sympathetic muscuranic control.

HYPO THALAMUS SET- PO INT FO R BO DY TEMP :
* Te mp se nsors on the skin a nd hypotha la mus re a d the c ore te mp and re la y informa tion to a nt hyp otha la mus which
compare core temp with SET- POINTtemp.
* If core temp is below or above normal it activate SET- POINTheat generating or losing mechanism via Post
hyp otha la mus.
* Cold and Pyogens ( infla mma tory produc ts and media tors ) | the SET- POINTtemp.

36

FEVER : Pyogens produce IL-1 which act on ant hypothalamus to | the production of prostaglandins which | the SET
POINTtemp and generate heat (fever).

HEAT EXHAUSTION AND HEAT STO RK :
* He a t e xha ustion: is caused by excessive sweating + Blood vol + BP Syncope .
* He a t stork: occur when body temp | to the point of tissue damage due to impaired sweating response | core
temp.
* Hyp othe rmia : results when temp is low and shivering & metabolism can not adequately maintain core temp near
SETPOINT.
* M a lig na nt hyp e rthe rmia : caused by inhalation anesthetics in susceptible individual. It is characterized by | in O 2
c onsump tion a nd he a t p rod uc tion b y ske le ta l musc le rapid | in body temp.
----------------------------------------------------------------------

Fe w Points
* Renshaw cells (neuron) respond to Ach and receptor is nicotinic.
* Parasympathetics contract smooth muscle but relax sphincter by muscarinic receptors.
* Sympathetics relax smooth muscle and contract sphincters by o receptors. exception in eye where o receptors
contract radial muscle and cause mydriasis.
* |1 -- In heart cause contraction where as in kidney cause Renin release.
* |2 -- Relax smooth muscle
* |3 -- In Adipose tissue lipolysis.

* In carotid sinus Baro receptors respond strong to rising Pressure than falling pressure.
* Protein produce by platelets is thromboplastin.
* Cerebellar lesion cause intention tremor (tremor during voluntary movement). vs.
Parkinson dis cause resting tremor. Imp d iffe re nc e
* Difference b/ w decerebrate and decortical rigidity and other signs ?

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