General Physiology 2.
0
Body fluid compartments
D20 / T20/ Antipyrine Age-
Male > Female
Q. A patient injected with 500mg of
mannitol. The concentration of mannitol in
plasma is 3mg/dl. During the equilibirium
period, 10% mannitol is excreted in the
urine. What is the volume being estimated
and which compartment does it belong to?
RISA
Evans Blue
(T-1824)
Mannitol
Sucrose
Inulin
Na thiosulfate
Darrow-Yannet diagrams
Loss of isotonic fluid Gain of isotonic fluid
Loss of hypotonic fluid
Gain of hypotonic fluid
Loss of hypertonic fluid
Gain of hypertonic fluid
Nerve action potential
ARP:
Hyperkalemia-effect on RMP:
E-C coupling
Intracellular Ca
Absence of Ca:
Absence of ATP:
Electromechanical coupling:
DHPR (Ca V1)-RYR1coupling
Electro-chemical coupling
DHPR (CaV2)-RYR2 coupling
CICR
Muscle reflex
Reflex Type Stimulus Afferent Response
Stretch
reflex/
Spindle
Golgi
tendon
During contraction:
Prominent-
Disappear-
Shorten-
Constant-
Epithelial cell junctions
JAM
Cytoskeleton
Muscle contraction Movement, cell division Maintain cell structure
Cytokinesis Cilia, flagella, mitotic spindle,
Actin, microvilli centriole, axoplamic transport in
Cytokeratin:
neurons Desmin:
Vimentin:
GFAP:
Retrograde:
Antegrade:
EXERCISE PHYSIOLOGY
Isotonic exercise: Isometric exercise:
CO: CO:
HR: HR:
SV: SV:
SBP: SBP:
TPR: TPR:
DBP: DBP:
MAP: MAP:
Blood flow:
Muscular > Coronary > Cerebral >
Renal/ Splanchnic
MV: V/Q ratio:
ODC:
PvO2
PvCO2
Miscellaneous
Nerst equation-Equilibrium potential Gibbs Donnan : Diffusion of permeable ions
changes due to large impermeable molecule
Na: +60 mV like protein
Ca: +100 mV
Cl: -70mV Coughing:
K: -90V ` Deep inspiration -> forced expiration against
closed glottis -> sudden glottis opening
Sneeze: forced expiration against open glottis
FEEDBACK:
Goldman equation: Calculate RMP Baroreceptor reflex:
• RMP of cell closest to RMP of K due to open leaky Parturition
channels Clotting
LH surge
Gain = Correction / Error Salivation on thinking about food:
Exercise
Endocrine: Temperature
Autocrine:
Paracrine: • Carrageenan theory:
Juxtacrine: • Bitter taste transmitted by:
• TENS:
Miscellaneous
Altitude: Diving:
FiO2: Barotrauma –
Pao2: Caisson disease-
Ventilation:
Acid-base:
2,3BPG:
PVR:
Acute mountain sickness:
HAPE:
HACE:
GENERAL PATHOLOGY 2.0
Cell injury
Amorphous densities
Myelin figures in mitochondria
(peroxidized lipids)
AI Lymphoproliferative syndrome
Cell membrane typically remains intact without inflammation
PCD with RIPK-1 and MLKL
phosphorylation-
PCD with Caspase 1,4,5,11-
PCD with iron – Phosphatidyl serine flipping-Annexin V: “Eat me”
(fenton reaction/lipid peroxidation) Tunel stain
INFLAMMATION
VASODILATION
CD31
Increased permeability CD62
Bombay blood Delayed separation of
group cord
No pus
1L-2, IL-12, INF-G:
IL-4, IL-5, IL-13:
IL-1, IL-6, TNF-A:
1L-10, TGF-B, Lipoxin:
EXTRAVASATION
IL-8, C5a, LTB4, 5HETE, Kallikrein:
Site:
C3b, IgG:
C3a, c5a:
INFLAMMATION
GRANULOMAS:
Caseating-
Non-caseating-
Histiocytes in gumma-
Stellate-
Durck-
Doughnut-
Listeria
Schistosomiasis
CGD
PBC
GPA, EGPA, Takayasu
De Quervian
Berylliosis, HSP, Talcosis
IMMUNE CHECK POINT INHIBITORS
Advanced melanoma, RCC
Melanoma
HL
NSCLL
UB
Merkel cell ca
T cell receptor: Gamma-delta:
Immunology
Affinity maturation-Somatic hypermutation
Isotype switching-Alternate RNA splicing
Hyper IgM disease
Complement pathway
MC complement deficiency:
Early complement deficiency:
Terminal comp /MAC def:
C1 INH def:
CD16, 56, 94:
CD41, 42, 61:
Leukocyte common Ag:
CALLA:
Positive selection:
Negative selection:
AIRE in thymus:
IPEX (Immune dysregulation,
Polyendocrinopathy, Enteropathy, X-linked)
syndrome : FOXP3 defect
Immunodeficiency disorders
Recurrent infections since Birth
ADA : AR
Absent germinal centers/
thymus
Thrombocytopenia Facies Lyst, Light
Infections Abscess-Cold Microtubule
Eczema- High IgE Teeth Neurodegeneration
XLR Eczema-IgE high phagOlysosome
Platelet, Neutrophil dense
granules
Amyloidosis
Amyloidosis Fibril protein
Primary amyloidosis
Secondary amyloidosis
Dialysis-related
Alzheimer disease
Type 2 diabetes mellitus
Medullary thyroid cancer
Isolated atrial amyloidosis
Systemic senile amyloidosis
Negative APR:
Amyloid polyneuropathy Albumin, Antithrombin Transferrin,
Transthyretin, Transcortin
Pedigree Analysis
STEPWISE:
No gender pref
(65%) All generations affected
No gender pref
(25%) Generations skipped
Mother to ALL
Father to ALL sons
Father to all daughters
Mother to 50% kids
Males affected, females carrier
+ Generations skipped
Surprise case!
Trinucleotide repeat disorders
Diagnosis
Repeat
Inheritance
Chromosome
Gene
Others
NEOPLASIA-PROTONCOGENIC GENES
Proto-oncogenes Tumor-suppressor genes
KRAS P53 -> P21 (Inhibits G1-S)
HRAS RB (inhibits G1-S)
NRAS APC
GNAQ NFI
GNAS NF2
C MYC
PTCH (inhibits SHH)
L MYC
PTEN
N MYC
SMAD2, SMAD4
ALK
RET VHL (HIF)
ABL STK11
C-KIT SDH
NOTCH CDH1
FLT3 BRCA1
ERBB1=EGFR BRCA 2
ERBB2=HER MSH2 / MLH1
BRAF WT1
CYCLIN D1 MEN1
NEOPLASIA
Tumor markers
AFP
CEA
CA-125
CA 15-3, CA 27-9
CA-19-9
CA 72-4
CK7– CK20 +
CK7 + CK 20 +
Field cancerization: Chemical Carcinogens:
Head and neck ca Aflatoxin-
Skin ca Arsenic
Bladder ca
Vinyl chloride
Aromatic dyes (Benzidine)-
Benzene-
INHERITANCE
HLA
HS, VWD
B27:
Marfan, Achondroplasia
B57:
AIP
B51:
MEN, Neurocutaneous syndromes
DQ2 / DQ8:
DR2:
All inborn errors of metabolism
DR3:
CF
DR4:
Wilson, Menkes kinky hair, Hemochromatosis
Cw6:
CAH
A3:
Sickle cell anemia, Thalassemia
DMD/ BMD
Hemophilia A / B /C
G6PD
Wiscott Aldrich/ Bruton’s
Lesch Nyhan
RP
Alport
X-linked hypophosphatemic rickets
IP
Hypersensitivity Reactions
• Autoimmune hemolytic anemia • Serum sickness, Arthus • Contact dermatitis
• Immune thrombocytopenia reaction • Graft-versus-host disease
• Transfusion reactions • SLE (2 and 3) • PPD for TB infection
• IgA vasculitis
• Hemolytic disease of the newborn • Patch test
• Polyarteritis nodosa
• Good pasture syndrome • Post-streptococcal • Lepromin test
• Rheumatic fever glomerulonephritis • Montenegro test
• Hyperacute transplant rejection • Rheumatoid arthritis • Transplant rejection-
• Pemphigus (3>4) Chronic
• Reactive arthritis
• Myasthenia gravis • Hypersensitivity
• Graves disease pneumonitis(3/4)
Transplant immunology
Autograft:
Isograft:
Allograft/ Homograft:
Xenograft/ Heterograft:
Most important HLA:
MC infection (1-3month) post
transplant:
GVHD:
High-yield
Aging: Cell adaptation
Telomere shortening-Hayflick Hypertrophy:
limit: Hyperplasia:
Muscles during weight lifting
Free radical mediated damage
LVH
Breast during puberty
Sirtuins BPH
Histone deacetylase Endometrium after estrogen
Uterus during pregnancy
Metaplasia: Reversible?
Dystrophic calcification:
Metastatic calcification:
Vacutainer Color Additive Use
GENERAL PHARMACOLOGY 2.0
Formulae:
Volume of distribution
Plasma protein binding:
Lipid solubility:
Loading dose: Target conc x Vd
Maintanence dose: Target conc x CL
Therapeutic index TI= Median toxic dose /median effective dose
TD50/ED50
Potency VS Efficacy
Competitive antagonist:
Non-competitive:
Phenytoin
Warfarin
Ethanol
Aspirin
a. Aspirin+ PCM (2+2=4)
b. Clopidogrel + Aspirin (2+2>4)
c. Carbidopa-Levodopa (2+0>2)
Permissive
General Pharmacology tables
Enzyme inducers Enzyme inhibitors Gynecomastia CYP2C19:
Griseofulvin Valproate CLOPIDOGREL -> active
Phenobarbitone Ketoconazole
CYP2C9: both zero order
Phenytoin Cimetidine
WARFARIN
Rifampicin Omeprazole PHENYTOIN
Carbamazepine Ciprofloxacin
Nevirapine Erythromycin CYP 3A4
Smoking, Ethanol INH CAT
Cisapride
Aminophylline: Essential drugs : Schedules: Astemizole
PDE-4 inhibition Under medical supervision: Terfenadine
PDE-3 inhibition Cost effective With prescription only: OCP(ESTROGEN)
Adenosine antagonism Prevalent Cannot be treated: Cyclosporine/ Tacrolimus
Histone deacetylase diseases Addictive potential: Statins / AMiodarone
activation Available easily Category:
No combination X: CYP2D6
TAMOXIFEN -> active
500mg PCM containing only 200mg PCM: Bblocker
500mg PCM containing only no PCM: SSRI
500mg PCM containing harmful substances:
Drugs for rare diseases:
Trandermal patch PRODRUGS:
Carbimazole
Nicotine patch Clopidogrel
Hyoscine Prednisone
Diphenhydramine Prasugrel
Nitrates Levodopa
Clonidine ACE- except:
Seligiline Sulfasalazine
Rivastigmine Mycophenolate
Bioequivalence: 80-125% Ritogitine Acyclovir/ Gancyclovir
HRT
Anti-obesity Approved drugs: Suicide inhibitors:
High first pass metabolism: Phentermine + topiramate PPI
Lignocaine Bupropion + zonisamide MAO inhibitors
Fentanyl Liraglutide, Semaglutide OP
Natural steroids-GC, MC, E, PR Tirzepatide Aspirin
Propranolol Orlistat, Cetilistat
Morphine
Verapamil
Salbutamol
Nitrates
Imipramine
ANS
Agonist: BETHANECHOL
Antagonist: Solifenacin, Oxybutynin,
Flavoxate, Tolterodine, Darfenacine
MIRABEGRON
TAMSULOSIN
M1
M2
M3
CHOLINERGIC / ANTICHOLINERGIC
CHOLINERGIC
Bethanechol
Carbachol
Methacholine
Pilocarpine
Donepezil, Rivastigmine, Galantamine
Neostigmine
Pyridostigmine
Physostigmine
Varenicline
ANTI- CHOLINERGIC
Atropine, Homatropine, Tropicamide
Benztropine, Trihexyphenidyl
Glycopyrrolate
Hyoscyamine, Dicyclomine
Ipratropium, Tiotropium
Solifenacin, Oxybutynin, Flavoxate, Tolterodine, Darfenacine
Scopolamine
Pirenzepine
BT
Adrenergic agonists/ antagonists
Receptors
a1 BV: PUPIL: UB/Viscera:
Agonist-Phenylephrine, Midodrine
Antagonist-Phenoxybenzamine
Phentolamine
Selective alpha-1: Prazosin, Terazosin, Doxazosin
Tamsulosin
a2
Agonist- Clonidine, Methyldopa
Antagonist-Yohimibe
b1 HR: Renin +
Agonist-Dobutamine
b2 BV: Bowel-bladder-uterus: Bronchus:
Tremor: Sugar:
Agonist-Salbutamol, terbutaline
Antagonist-Butoxamine Indirect agonists
Amphetamine
b3 Lipolysis Cocaine
Agonist-Merabegron Ephedrine
Beta Blockers
BETA BLOCKERS USES: CI:
B1 selective: CVS Bradycardia
Atenolol,Betaxolol, Bisoprolol, Esmolol, Metoprolol Glaucoma AV block
Nebivolol: Performance anxiety Acute CHF
Celiprolol: Thyroid storm Asthma
Acebutolol: Akathisia PVD
Migraine prophylaxis DM
Non-selective: Essential tremors Prinzmetal angina
Nadolol: DOC for toxicity:
Propranolol:
Timolol Bisoprolol, carvedilol, metoprolol
Pindolol:
Nadolol, Propranolol, Carvedilol
Alpha + beta blockers: Carvedilol, Labetalol
Tillisolol:
Sotalol:
ANS graphs
DOC
Norepinephrine
Septic shock, Neurogenic shock
Cardiogenic shock-refractory Epinephrine
Cardiogenic shock Isoproterenol
Cardiogenic shock + oliguria
CPR, Anaphylactic shock
Postural hypotension
Spinal induced hypotension
DOPAMINE
<2 ug/kg/min
2-10
>10
PG analogues
PDE-5 inhibitors
Sildenafil , vardenafil , tadalafil
PDE-4 inhibitor
Roflumilast
PDE-3 inhibitor
Milrinone
“Platelet inhibitors”
Cilostazol
Dipyridamole
Anti-microbials
Safe in renal failure:
PMT
Cyp inh, QT prolong, tendons, seizure
Cyp inh, QT prolong,
Prokinetic, Jaundice
Fosfomycin:
Muramic acid
Cycloserine:
Pentapeptide (d-
ALA)
Bacitracin:
BP transporter
Vancomycin:
Transglycosylase
B lactams:
Transpeptidase
No cross-reactivity:
DOC:
Syphilis, Actinomyces
Listeria
Mastitis
SSI
Neisseria, Lyme disease (complicated), Enteric fever
Enterobacter, Acinetobacter
Plague,Tularemia
Ricketsia, Cholera
Atypical pneumonia, Legionella, Mycoplasma, Chlamydia, Pertussis, Diphtheria
Nocardia, PCP, Burkholderia, Cyclospora, Isospora
Meningococcal, Anthrax, UTI, Travelers diarrhea
Ceftriaxone, Cefoperazone: Imipenem+ Cilastatin:
Bile excretion
TABLE OF DRUGS NOT EFFECTIVE AGAINST MICROORGANISMS
MYCOPLASMA Cell wall inhibitors (beta-lactams, vancomycin)
PSEUDOMONAS Vancomycin
ANAEROBES Aminoglycosides
MRSA Beta lactams (except fifth generation cephalosporins)
SALMONELLA Aminoglycosides
VRSA: Resistance: Enzyme Altered target Efflux pump
Linezolid
Daptomycin
Quinpristine-Dalfopristine
Ceftarolin
CIDAL DRUGS
BEVAFA STREPTOGRAMINS
Antifungals
• Systemic severe infection, Mucor, Kalaazar DOC:
• Infusion reaction, Nephrotoxicity, RTA type 1, hypokalemia, BM supression:
• Cryptococcal DOC:
• Candida DOC, Max oral / CNS BA:
• Aspergillus DOC, Transient visual changes:
• Histoplasmosis, Sporothrix, Blastomyces DOC:
• Azole useful in mucor:
• Azole with antipruritc/ anti-inflammatory action
• Antifungal causing heart failure:
Anti-cancer drugs
Hemorrhagic cystitis
Compound:
Prevention:
Treatment:
Cyclophosphamide
Busulfan
Bleomycin
Carmustine
Methotrexate
Amiodarone
Vincristine
Bleomycin
L-aspararginase
Ribonucleotide reductase
DHF reductase
ADA
Fludarabine Mitomycin C
Temozolamide Nephrotoxic:
Ototoxic
5FU / Capecitabine s/e: Most emetogenic
DOC early-
Anthracycline s/e: DOC delayed-
Anticancer small molecule inhibitors
NEW DRUGS Alectinib, crizotinib ALK Non-small cell lung
Vismodegib cancer
Osimertinib : T790M mutation Erlotinib, gefitinib, EGFR Non-small cell lung
Belimumab: afatinib L858R mutation cancer
Teprotumumab: Imatinib, dasatinib, BCR-ABL CML, ALL, GISTs
Elacestrant, Fluvestrant: nilotinib
Teplizumab: Ruxolitinib JAK1/2 Polycythemia vera
Omavexolone: Bortezomib, Proteasome Multiple myeloma,
Ravulizumab, Rozanolixizumab: ixazomib, carfilzomib (induce G2-M mantle cell
Daprodustat: arrest -> lymphoma
Vanoprazan: apoptosis)
Palivizumab Vemurafenib, BRAF Melanoma
Cetuximab, Panitumumab encorafenib,
Emicizumab dabrafenib
Palbociclib Cyclin- Breast cancer
Natalizumab
dependent
IFN-α
kinase 4/6
IFN-β (induces arrest
IFN-γ at GI-S phase →
Aldesleukin apoptosis)
Olaparib Poly(ADP-ribose) Breast, ovarian,
Ixekizumab, Secukikumab polymerase (↓ pancreatic and
Risankizumab, Guselkumab, Tildrakizumab DNA repair) prostate cancers
Ustekinumab ALEMTUZUMAB CD52 CLL