Basic Sciences Stuff Flashcards

(145 cards)

1
Q

Red cell Indices
MCV, MCHC, MCH, RBCmass

A

MCV: Mean corpuscular volume (MCV) is the average volume of a red blood cell and is calculated by dividing the hematocrit (Hct) by the concentration of red blood cell count.
# MCV =Hct/ [RBC COUNT]
Normal range: 80–100 fL (femtoliter)

MCH: Mean corpuscular hemoglobin is the average amount of hemoglobin (Hb) per red blood cell and is calculated by dividing the hemoglobin by the red blood cell count.
MCH= {Hb} / {RBC}}
Normal range: 27-31 pg/cell

MCHC: Mean corpuscular hemoglobin concentration is the average concentration of hemoglobin per unit volume of red blood cells and is calculated by dividing the hemoglobin by the hematocrit.
MCHC= {Hb} / {Hct}}
Normal range: 32-36 g/dL

Red blood cell distribution width (RDW or RDW-CV or RCDW and RDW-SD) is a measure of the range of variation of red blood cell (RBC) volume, yielding clues about morphology

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2
Q

Iron Profile
Normal reference ranges are:

Serum iron:
= Men: 65 to 176 μg/dL
= Women: 50 to 170 μg/dL
= Newborns: 100 to 250 μg/dL
= Children: 50 to 120 μg/dL
TIBC: 240–450 μg/dL
Transferrin saturation: 20–50%

A

Serum iron is a medical laboratory test that measures the amount of circulating iron that is bound to transferrin and freely circulate in the blood.
65% of the iron in the body is bound up in hemoglobin molecules in red blood cells.
About 4% is bound up in myoglobin molecules.
Around 30% of the iron in the body is stored as ferritin or hemosiderin in the spleen, the bone marrow and the liver.
Small amounts of iron can be found in other molecules in cells throughout the body. However, some iron is circulating in the serum. Transferrin is a molecule produced by the liver that binds one or two iron(III) ions, i.e. ferric iron, Fe3+; transferrin is essential if stored iron is to be moved and used. Most of the time, about 30% of the available sites on the transferrin molecule are filled. The test for serum iron uses blood drawn from veins to measure the iron ions that are bound to transferrin and circulating in the blood. This test should be done after 12 hours of fasting. The extent to which sites on transferrin molecules are filled by iron ions can be another helpful clinical indicator, known as percent transferrin saturation.
Another lab test saturates the sample to measure the total amount of transferrin; this test is called total iron-binding capacity (TIBC). These three tests are generally done at the same time, and taken together are an important part of the diagnostic process for conditions such as anemia, iron deficiency anemia, anemia of chronic disease and haemochromatosis.

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3
Q

C Reactive Proteins

A

C-reactive protein (CRP) was discovered by Tillett and Francis in 1930. The name CRP arose because it was first identified as a substance in the serum of patients with acute inflammation that reacted with the “c” carbohydrate antigen of the capsule of pneumococcus.

CRP is a pentameric protein synthesized by the liver, whose level rises in response to inflammation. CRP is an acute-phase reactant protein that is primarily induced by the IL-6 action on the gene responsible for the transcription of CRP during the acute phase of an inflammatory/infectious process.

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4
Q

Foot -Muscles-Movements-Nerves

A

Plantar Flexion:
= downgoing as accelerating car
= Gastrocnemius, Soleus
= Sciatic S1

Foot dorsiflexion:
= Tibialis anterior (L4L5)
= Long foot Extensors (Sciatic, common peroneal nerve)

Foot inversion:
= Tibialis anterior & Posterior (L4, Tibial)
Foot Eversion:
= Peronei (S1, Sciatic, common pero)

Great Toe Extension:
= Extensor Hallucis longus, L5

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5
Q

Peripheral Neuron

A

There are three types of fibers that carry pain signals to the brain — A-beta, A-delta and C-fibers. The first two are evolutionarily modern fibers that are myelinated (insulated) and carry nerve impulses rapidly to the cortical regions of the brain
The C-fibers are relatively primitive, are unmyelinated and conduct rather slowly to the subcortical part of the brain. The brain perceives a more generalized burning, aching pain sensation, and this pain takes longer to pass.

Types
A beta type: Large, myelinated, Afferent to skin, Light touch, Moving stimuli
A delta type: Small fiber, myelinated, afferent to pain stimuli
C type axons: unmyelinated, afferent (sensory) slow

Sympathetic Post-Ganglionic: unmyelinated

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6
Q

Pituitary Hormones

A

Anterior pituitary:
= Growth Hormone
= Prolactin
= Thyroid stimulating Hormone (TSH)
= Adrenocorticotropin Hormone (ACTH)
= Follicle stimulating hormone (FSH)
= Leutinizing Hormone (LH)

Posterior Hormone:
= Anti-diuretic Hormone (Vasopressin)
= Oxytocin
= Melanocyte stimulating hormone

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7
Q

Blood pressure formula

A

= Cardiac Output x SVR (systemic vascular resistance)
ie
= (Heart Rate x Stroke volume) x SVR

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8
Q

Ortbial Apex and Superio Orbital fissure contents:

A

The orbital apex incorporates the optic canal and the superior orbital fissure. The optic canal transmits the optic nerve (surrounded by meninges) and the ophthalmic artery to the cranial fossa. The superior orbital fissure is anatomically lateral to the optic canal which can be divided into the superior, middle, and inferior portions by the common tendinous ring comprised of the thickened periorbita lining the surface of the orbital bones. The contents of the optic canal and the middle portion of the superior orbital fissure course through the common tendinous ring. The superior portion transmits the lacrimal nerve (CNV1), frontal nerve (CNV1), trochlear nerve (CNIV), superior branch of the ophthalmic vein, and recurrent meningeal artery. The middle portion transmits the nasociliary nerve (CN V1), abducens nerve (CNVI), and the superior and inferior branches of the oculomotor nerve (CNIII). The inferior portion transmits the inferior branch of the ophthalmic vein.

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9
Q

Vitamin B12

A

Cyanacobalamine:
water soluble, essential ie not made in body
co-factor in DNA synthesis
Absorbed in distal ileum

Deficiency causes: fatigue, High MCV anemia, paraesthesia, Headache. Sore red tongue, SACD if long standing

Pernicious anemia: (Antiparietal cell and Anti Intrinsic factor antibodies)
Post Gastrectomy (IF secreted here)
Post Ileal resect (B12 absorbed here)
Intrinsic factor deficiency
Malabsorption: coeliac, Sprue
Pure vegan diet

Rx - always replace before folate, iron or transferrin because neuropathies will occur otherwise.
IM Dose alternate days x 2 weeks
then every 3 months for life

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10
Q

Anti-diuretic Hormone, Vasopressin

A

secreted by hypothalamus and stored in posterior pituitary
acts on collecting ducts through AVP RECEPTORs which inserts aquaporine channels leading to more water absorption. (anti diuresis action)

  • Defect in AVR2 or Vasopressin 2
  • Defect in aquaporin 2 channels
    both these will leads to nephrogenic Diabetes insipidus due to low action of ADH - more diuresis and severe dehydration, Hypernatremia due to Na retention and water loss.
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11
Q

Aldosterone

A

Hormone secreted by adrenal zona glomerulosa in response to angiotensin II and K. Acts on distal tubules of nephron via H-K-channel leading to
Na retention - hence
water retention
H loss
K loss

excess aldosterone causes Hypertension(Na gain)

Spironolactone - is an aldosternone antagonist drug competively inhibits Na-K exchange channel leading to H2O loss > Na loss and K retention ie hyperkalemia

Conn’s syndrome
aldosterone secreting tumor of adrenal - excess Aldosterone leads to Na retention, water retention, High resistant HTN, hypokalemia. There is mild metabolic alkalosis due to low K and increased blood volume.

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12
Q

Antinuclear Antibodies, ANA

A

can be Cytoplasmic or nuclear ANA
may be of type Homogenous-Speckled-Nuclear-Centromere
1:160 is high titre
checked by ELISA, Immunofluoroscence
Speckled ANA: Ro, La, U1-RNP
Nuclear, Centromere: = Scleroderma
ENA: Extractable nuclear antigens

Anti ds-DNA: SLE
Anti Phospholipid: APLS
Anti-Topoisomerase-1(Scl-70): Systemic sclerosis
Anti Ro, La: Sjogren’s ie keratoconjunctivitis sicca
Anti Jo1, Mi2: Polymyositis

ANCA-Anti-neutrophillic-cytoplasmic antibody
c-ANCA (proteinase-3, PR3) = Vasculitis
p-ANCA (myeloperoxidase, MPO) = Vasculitis
C for cytoplasmic, p for perinuclear, fluoroscopic patterns
- Granulomatosis with polyangitis (Wegner’s)
- Eosinophillic granulomatosis with polyangitis (Churg Strauss syn)
- Microscopic polyangitis

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13
Q

Liver screen

A

Liver function tests
Hepatitis B & C screen
Immunoglobulins
Anti mitochondrial antibody
Anti smooth muscle antibody
Anti Liver Kidney microsomal AB
Anti nuclear antibody
Ferritin levels
Alfa 1 anyitrypsine levels
Coagulation profile
Gamma GTT
Alfa fetoprotein
Caeruloplasmin
Ultrasound liver

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14
Q

Alfa fetoprotein

A

AFP is a major plasma protein produced by the yolk sac and the fetal liver during fetal development. It is thought to be the fetal analog of serum albumin. AFP binds to copper, nickel, fatty acids and bilirubin and is found in monomeric, dimeric and trimeric forms.

The function of AFP in adult humans is unknown. AFP is the most abundant plasma protein found in the human fetus. Maternal plasma levels peak near the end of the first trimester, and begin decreasing prenatally at that time, then decrease rapidly after birth. Normal adult levels in the newborn are usually reached by the age of 8 to 12 months.

Measurement of AFP is generally used in two clinical contexts. First, it is measured in pregnant women through the analysis of maternal blood or amniotic fluid as a screening test for certain developmental abnormalities, such as aneuploidy. Second, serum AFP level is elevated in people with certain tumors, and so it is used as a biomarker to follow these diseases. Some of these diseases are listed below:

Developmental birth defects associated with elevated AFP
Omphalocele
Gastroschisis
Neural tube defects: ↑ α-fetoprotein in amniotic fluid & maternal serum

Tumors associated with elevated AFP
Hepatocellular carcinoma
Metastatic disease affecting the liver
Nonseminomatous germ cell tumors
Yolk sac tumor

Other conditions associated with elevated AFP
Ataxia telangiectasia: elevated AFP is used as one factor in diagnosis

A peptide derived from AFP that is referred to as AFPep is claimed to possess anti-cancer properties.

In the treatment of testicular cancer it is paramount to differentiate seminomatous and nonseminomatous tumors. This is typically done pathologically after removal of the testicle and confirmed by tumor markers. However, if the pathology is pure seminoma, if the AFP is elevated, the tumor is treated as a nonseminomatous tumor because it contains yolk sac (nonseminomatous) components.

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15
Q

Alfa 1 Antitrypsin

A

Alpha-1 antitrypsin or α1-antitrypsin (A1AT, α1AT, A1A, or AAT) is a protein belonging to the serpin superfamily. It is encoded in humans by the SERPINA1 gene. A protease inhibitor, it is also known as alpha1–proteinase inhibitor (A1PI) or alpha1-antiproteinase (A1AP) because it inhibits various proteases (not just trypsin). In older biomedical literature it was sometimes called serum trypsin inhibitor (STI, dated terminology), because its capability as a trypsin inhibitor was a salient feature of its early study. As a type of enzyme inhibitor, it protects tissues from enzymes of inflammatory cells, especially neutrophil elastase, and has a reference range in blood of 0.9–2.3 g/L (in the US the reference range is expressed as mg/dL or micromoles), but the concentration can rise manyfold upon acute inflammation.

When the blood contains inadequate amounts of A1AT or functionally defective A1AT (such as in alpha-1 antitrypsin deficiency), neutrophil elastase is excessively free to break down elastin, degrading the elasticity of the lungs, which results in respiratory complications, such as chronic obstructive pulmonary disease, in adults. Normally, A1AT leaves its site of origin, the liver, and joins the systemic circulation; defective A1AT can fail to do so, building up in the liver, which results in cirrhosis in either adults or children

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16
Q

Gastric Hormones

A

Gastrin: secreted by G cells of gastric antrum, increased by vagus stimulation and reduced by Low PH and somatostatin. Increases HCl production, pepsinogen, motility and Intrinsic factor levels

Cholecystokinin: secreted by I cell of proximal small intestine. Secretion stimulated by TG and protein meals. Increases pancreatic secretions, causes GB contraction releasing bile, increases satiety and reduces gastric emptying.

Secretin: by S cells in proximal small intestine. Stimulated by acidic chyme and Fatty acids in it. Increased HCO3 rich pancreatic secretions and reduces gastric acid secretion.

Vasoactive Intestinal Peptide: produced by pancreas and small intestine, also increased by neural input. Increased pancreatic and intestinal secretions, reduces gastric acid production. Excess VIP causes secretory diarrhea as in VIPomas.

SomatoStatin: produced by D cells in stomach and pancreas. Secretion stimulated by Fatty acids, glucose and bile. Inhibitory action, reduces acid/ pepsin/ gastrin and insulin secretion and production.

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17
Q

Spinal Pathways

A

Descending- Motor:
= Pyramidal tracts: Anterior cortico-spinal and Lateral cortico-spinal
= Extra-Pyramidal: Rubrospinal, Reticulospinal, Olivospinal, Vestibulospinal
—————————
Ascending Sensory:
= Dorsal columns-Medial Leminiscus system: Gracile fasciculus, Cuneate fasciculus
= Spino-cerebellar: Anterior, Posterior
= Spino-Thalamic: Anterior, Lateral

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18
Q

Cranial Nerves: Sensory/Motor

A

Some Say Marry Money But My Brother Says Big Brains Matter Most
S = sensory
M = Motor
M = Mixed
1-12 each word in sequence

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19
Q

Retro-peritoneal structures

A

SAD PUCKER:
- Supra renal glands
- Aorta
- Duodenum except 1st part
- Pancreas except tail
- Ureters
- Colon (ascending, descending)
- Kidneys
- Esophagus
- Rectum

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20
Q

Testosterone

A

It is responsible for development of internal genitalia and spermatogenesis. IT IS converted to dihydro-testesterone by enzyme 5 alfa-reductase which is more active form and responsible for development of male secondary sexual characters. Absence of this enzyme or DHT receptor leads to testicular feminization.

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21
Q

Melatonin

A

Synthesized from serotonin and secreted by pineal gland, causes sleep
Stimulation of release:
= Exposure to darkness
= Retino-Hypothalamic nerves
= Due to Norepinephrine released by post-ganglionic sympathetic nerves (nervi conarnii)
which innervates pineal gland

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22
Q

Rheumatoid Factor

A

an IgM antibody against patient own IgG Fc

Detected by Rose waaler Assay using sheep rbc agglutination or by Latex agglutination

70-80% positive in Rheumatoid arthritis
Also can be present in:
- Sjogren’s syndrome (100%)
- Felty’s syndrome (100%)
- Infective endocarditis
- SLE
- Systemic sclerosis
- General population
Rarely: TB, HSV, EBV, Leprosy infections

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23
Q

Parathyroid Hormone

A

Secreted by 4 parathyroid glands
84 amino acids peptide

Stimulation of release: Hypocalcemia, Low VitD

Inhibition of release: HypoMg, Hypercalcemia, Hypervitaminosis D

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24
Q

Small Hand Muscles

A

Abductor Pollicis brevis (APB): thumb Abduction, test by Palm, thumb to ceiling, dont let me push down your thumb to palm

First Dorsal Interossei: index finger: Test as palm up and push index out against resistance

Abductor digiti minimi:
little finger abduction, test by pushing out little finger against resistance

APB weak + 1st DI weak = T1 radiculopathy
APB weak + 1st DI spared = Median nerve lesion
APB intact + 1st DI weak = Ulnar nerve lesion

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25
Lung volumes, 01
**TLC, Total lung capacity**: the volume in the lungs at maximal inflation, the sum of VC and RV. **TV, Tidal volume**: that volume of air moved into or out of the lungs during quiet breathing (TV indicates a subdivision of the lung; when tidal volume is precisely measured, as in gas exchange calculation, the symbol TV or VT is used.) **RV, Residual volume**: the volume of air remaining in the lungs after a maximal exhalation **ERV, Expiratory reserve volume**: the maximal volume of air that can be exhaled from the end-expiratory position **IRV, Inspiratory reserve volume**: the maximal volume that can be inhaled from the end-inspiratory level **IC, Inspiratory capacity**: the sum of IRV and TV IVC, Inspiratory vital capacity: the maximum volume of air inhaled from the point of maximum expiration **VC, Vital capacity**: the volume of air breathed out after the deepest inhalation. **FRC, Functional residual capacity**: the volume in the lungs at the end-expiratory position RV/TLC%, Residual volume expressed as percent of TLC
26
Lung Volumes, 02
VA, Alveolar gas volume VL, Actual volume of the lung including the volume of the conducting airway. FVC, Forced vital capacity: the determination of the vital capacity from a maximally forced expiratory effort FEV, tForced expiratory volume (time): a generic term indicating the volume of air exhaled under forced conditions in the first t seconds FEV1, Volume that has been exhaled at the end of the first second of forced expiration FEFx, Forced expiratory flow related to some portion of the FVC curve; modifiers refer to amount of FVC already exhaled FEFmax, The maximum instantaneous flow achieved during a FVC maneuver FIF, Forced inspiratory flow: (Specific measurement of the forced inspiratory curve is denoted by nomenclature analogous to that for the forced expiratory curve. For example, maximum inspiratory flow is denoted FIFmax. Unless otherwise specified, volume qualifiers indicate the volume inspired from RV at the point of measurement.) PEF, Peak expiratory flow: The highest forced expiratory flow measured with a peak flow meter MVV, Maximal voluntary ventilation: volume of air expired in a specified period during repetitive maximal effort
27
Oxygen Index
calculated for premature babies OI = (FiO2 X Mean Airway pressure) / PaO2 > 40 - consider ECMO support
28
Hormones & Second Messengers
**cAMP** = Adrenaline, GHRH, Glucagon, LH, FSH, PTH, TSH **MAP kinase pathway**: Insulin, GH, Prolactin **Ca++/Phospoinositide**: TRH, GnRH, Vasopressin **cGMP**: = Nitric Oxide, ANP **Intra-cellular receptors** = for T3 thyroxine **Cytosolic receptors**: = Steroids (Progesterones, Testosterone, Estradiol, Cortisol)
29
Nuclear Hormones
Corticosteroids Vitamin D Retinoic Acid Sex Steroids
30
Hering Breuer Lung Inflation Reflex
During normal breathing, vagal impulse activity of stretch receptors increases with onset of inspiration dying down as expiration begins. **Stimulation of stretch receptors by maximally inflating lungs in the humans INHIBITS INSPIRATION further** thereby limiting tidal volume and also slows respiratory rate, called as Hering Breuer reflex which is **protective** and important during exercise. It is **inactive in adults until tidal volume increases 1 Liter** - after which reflex increases respiratory rate and shortens inspiration.
31
Bohr Effect
Hydrogen ions reduce Hemoglobin’s affinity for oxygen by altering the structure of Hb so that it binds less easily to Oxygen and is known as **Bohr effect**.
32
Haldane effect
Haemoglobin reacts more readily with CO2 to form Carbamino compounds as it releases Oxygen increasing CO2 carrying capacity of blood. Opposite occurs as Hb is saturated with oxygen. Approximately 0.7 ml CO2 per 100 ml is unloaded for 1 mm Hg drop in CO2 pressure. Helps in minimising CO2 changes.
33
Genetic imprinting
for some genes either maternally or paternally derived, copy is preferentially used (not both) and other is inactivated **Examples** - 1. **Prader Villi Syndrome**: in 70% deletion on paternal chromosome 15, in 30% maternal uniparental disomy ie none from father. Has neonatal hypotonia, Poor feeding, moderate learning disability, Hyperphagia, Obesity, small genitals. 2. **Angelman syndrome**: 80% deletion on maternal chromosome 15, 2-3% paternal uniparental disomy. Happy puppet, unprovoked laughter or clapping, Microcephaly, severe learning disability, ataxia, Broad based gait, convulsions, EEG characteristic **Other examples**: Albrights hereditary Osteodystrophy Becekwith Wiedman Syndrome Russel Silver syndrome Familial Paraganglinomas (Pheochromocytoma)
34
Antibody Isotypes
**IgG**: monmeric, 1,2,3,4 > 75%, crosses placenta **IgM**: pentameric, first to respond to any new infection **IgE**: monomeric, binds allrgens, causes most degranulation involved in Type 1 hypersensivity reactions (inhibited by Omalizumab) **IgA**: dimeric, deficiency associated with auto-immunity as coeliac disease, mucosa association, IgA deficiency is **commonest Primary Variable deficiency**, = levels < 0.05 gms/Lit = presents as recurrent otitis media, pneumonias, Chronic sinusitis, reactions to blood products (check anti IgA antibodies prior to transfusions) **IgD**: monomeric, Hyper-IgD- syndrome is a rare autosomal recessive condition with periodic fevers
35
Cryoglobulins
Immunoglobulins which precipitates on exposure to cold as in cold fingers. these proteins may clump together at temperatures below 98.6 F (37 C). These gelatinous protein clumps can impede your blood circulation, which can damage your skin, joints, nerves and organs — particularly your kidneys and liver. **Presentation:** most commonly fatigue, joint pain, numbness or weakness, and a particular rash called **purpura** that looks like red spots or purple bruises, usually over the lower legs. **Type I Cryoglobulins** Monoclonal IgM cryoglobulins, causes hyperviscosity as in Waldernstrom's **Type II Cryoglobulins**: mixed mono/ polyclonal cryoglobulins seen with Hepatitis C, chronic infections **Type III Cryoglobulins**: Polyclonal cryoglobulins seen in CTDs as Sjogrens, SLE
36
Complement pathways
**Classic pathway**: Antigen + antibody = C1 complex activation = C1q, C1r, C1s = (C2 to C2a, C4 to C4a) = final common pathway = C5 TO C9 activation = membrane attack complex **Lectin Pathway**: Sugar residues on pathogens activates C2 +C4 then final common pathway follows **Alternative Pathway**: Bacterial, fungal cell wall, causes C3 activation to C3a, C3b =Factor B + D = Final common pathway of C5 to C9 activation = membrane attack complex formation deficiency in common final pathway increases Neisseria infections.
37
Phases of Action Potential
Phase 0 = depolarization and overshoot, initial upstroke Phase 1 = early repolarization to plateau voltage Phase 2 = Action potential plateau Phase 3 = full repolarization back to resting membrane potential Phase 4 = resting membrane potential with gradual depolarization during this phase in pacemaker cells
38
Blotting methods
**Southern Blot**: to transfer DNA fragments from a agar gel to a membrane **Western Blot**: proteins are transferred **Northern Blot**: RNA is bound to a membrane
39
Agar mediums A gelatinous material derived from certain marine algae. It is used as a base for bacterial culture media and as a stabilizer and thickener in many food products
**Blood agar**: grows most organisms **Chocolate agar**: for Haemophillus, Neisseria **Nutrient Broth**: for anaerobes **Cooked meat Broth**: aerobes, anaerobes **Brain Heart infusion Broth**: for fastidious organisms, fungi **Sabaraud's agar**: for fungi **Anaerobic Blood agar**: Peptococcus, propiniobacterium **Thioglycolate agar**: anaerobes **Lowenstein Jenson medium**: for TB **E coli seeded agar**: for Entamoeba
40
Essential Amino acids
PVT TIM HiLL 1. Phenyl alanine 2. Valine 3. Tryptophan 4. Threonine 5. Isoleucine 6. Methionine 7. Histidine 8. Leucine 9. Lysine
41
Human Leucocyte Antigens
encoded on chromosome 6 Class I HLA: = A, B, C Class II HLA: = DP, DQ, DR HLA-A3: = Haemochromatosis HLA-B5 = Behcet's disease HLA-B27 = Ankylosis, Reiters, Anterior uveitis HLA-DQ2/ DQ8 = Coeliac disease HLA-DR2 = Narcolepsy, Goodpastures HLA-DR3: = Primary biliary cirrhosis, Sjogrens, Dermatitis herpetiformis HLA-DR4 = Rheumatoid arthritis, IDDM
42
Major Histocompatibility complex, MHC
located on chromosome 6 short arm Encodes for proteins known as HLA which are expressed on surface of variety of cell types mainly leucocytes. Class I HLA (a,b,c) are expressed on virtually all body cells except RBCs and trophoblasts Class II HLA (dr, dq, dp) are expressed on B cells, monocytes, macrophages, follicular dendritic cells Most unstimulated T cells do NOT express class II antigens but they are induced to express them following antigen presentation/stimulation. Class I presents endogenous peptides to T cell receptor of CD8 cells Class II presents exogenous peptides to T cell receptors of CD4 types
43
Phases of cell Cycle
G0 phase: most cell in adult tissue are in this phase G1 phase: First gap phase, prior to initiation of DNA synthesis S phase: phase of DNA synthesis G2 phase: second gap phase, errors repaired here M phase: Mitosis phase, which completes cell cycle
44
Adrenal Hormones
**Adrenal Cortex**: **3 layers** Zona GFR-Miner Gluco Andro 1. **Zona Glomerulosa** (Outer): produces mineralocorticoids, 2. **Zona Fasciculata** (middle): produces glucocorticoids 3. **Zona Reticularis** (Inner): roduces androgen precursors (mostly DHEA with some androstenedione). Each layer produces steroid hormones synthesized from cholesterol. Adrenal **medulla** produces the catecholamines, epinephrine, and norepinephrine.
45
Hypothalamic-Pituitary-Adrenal Axis:
**Hypothalamic-Pituitary-Adrenal (HPA) Axis** - is involved in the production of glucocorticoids and adrenal androgens from the zona fasciculata and zona reticularis. In response to circadian rhythms or stressors, paraventricular neurons (PVN) in the hypothalamus make and secrete **corticotropin-releasing hormone** (CRH). CRH binds receptors on the anterior pituitary gland, which leads to the synthesis of ACTH (or corticotrophin) from pre-pro-opiomelanocortin (pre-POMC). Of note, cleavage of POMC also yields other hormones such as alpha-melanocyte-stimulating hormone (MSH). **ACTH from the anterior pituitary** is released into the circulation and engages the melanocortin type 2 receptors (MC2-R) in the zona fasciculata of the adrenal cortex predominantly to induce the synthesis of glucocorticoids. It is a GPCR and has an associated protein (MRAP) produced by the adrenal that appears to function as a chaperone to escort MC2-R to the cell surface to allow engagement by ACTH. Circulating glucocorticoids negatively feedback on the hypothalamus (long loop) and the anterior pituitary (short loop), suppressing the release of CRH and ACTH, respectively. This prevents the continued rise of glucocorticoid levels. ACTH is released from the anterior pituitary in a pulsatile pattern that parallels the fluctuating levels of cortisol. **Both ACTH and cortisol levels rise to a peak in the morning (6:00 AM to 8:00 AM)** and decline throughout the day, reaching their nadir at around midnight.
46
Renin-Angiotensin-Aldosterone system
**Renin-Angiotensin-Aldosterone-System** - The zona glomerulosa produces mineralocorticoids. While pituitary ACTH regulates adrenal glucocorticoid and androgen synthesis, it is not the primary regulator of mineralocorticoid synthesis. The 2 primary regulators of aldosterone are (1) the renin-angiotensin-aldosterone system (RAAS) and (2) potassium levels. The kidney releases renin in response to decreased renal perfusion sensed by the juxtaglomerular apparatus. Renin converts angiotensinogen to angiotensin I (AT-I), which is then converted to angiotensin II (AT-II) via angiotensin-converting enzyme (ACE) in the lung. **AT-II stimulates aldosterone synthesis in the zona glomerulosa by activating aldosterone synthase**.
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Mineralocorticoids
**Mineralocorticoids** The mineralocorticoids, which include: 1. **corticosterone**, 2. **11-deoxycorticosterone**, and 3. **aldosterone**, act on the kidney to increase sodium reabsorption and potassium excretion. Water reabsorption follows increased sodium reabsorption, resulting in an increase in effective circulating volume and therefore increased blood pressure. Specifically, mineralocorticoids achieve this via **increased synthesis of epithelial sodium channels (ENaC) and sodium-potassium ATPases** on the principal cells of the distal nephron. Mineralocorticoids also promote potassium ion secretion at the principal cells because of the gradients produced by the above channels. In high potassium states, aldosterone synthesis is increased to promote potassium excretion. Lastly, mineralocorticoids promote hydrogen ion secretion at the intercalated cells. Interestingly, 11-deoxycorticosterone and corticosterone also have mineralocorticoid effects. These are weaker than aldosterone but can produce a strong mineralocorticoid effect when present in excess levels, as in some forms of congenital adrenal hyperplasia (CAH), for example, 11-beta-hydroxylase deficiency resulting in hypertension.
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Glucocorticoids
Cortisol is the major glucocorticoid and increases in response to stress which activates the HPA axis. Therefore, all of its functions can be thought of as allowing the body to function with increased stress. Upon engaging glucocorticoid receptors, cortisol increases the expression of genes that will regulate metabolism, the immune system, cardiovascular function, growth, and reproduction. Cortisol is essential for maintaining blood pressure because it increases the sensitivity of vascular smooth muscle to vasoconstrictors like catecholamines and suppresses the release of vasodilators like nitrous oxide.[1] Cortisol suppresses the immune system, which is the basis for immunosuppressive drug therapy with glucocorticoids. Regarding metabolism, cortisol increases gluconeogenesis and decreases peripheral glucose uptake. These oppose the actions of insulin, and the net effect is an increase in serum glucose. Cortisol also activates lipolysis and stimulates adipocyte growth, which leads to fat deposition. Generally, growth is inhibited, leading to muscle atrophy, increased bone resorption, and thinning of the skin. Of note, glucocorticoids can act on mineralocorticoid receptors. However, aldosterone effects predominate in the kidney because the renal enzyme, 11-beta-hydroxysteroid dehydrogenase-2 (11-beta-HSD-2) converts cortisol to cortisone.[6] The 11-beta-HSD-1 converts cortisone into cortisol. Hence, these enzymes add another layer of regulation to cortisol. Licorice toxicity inhibits 11-beta-HSD-2, causing hypertension and hypokalemic alkalosis with normal aldosterone levels. Also, there can be a loss of function mutations in 11-beta-HSD-2, resulting in hypertension with low aldosterone.
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Androgens DHEA = Androstenedione = Testosterone = 5-alfa-dihydrotestosterone
The adrenal androgens, primarily **DHEA**, require **peripheral conversion to active sex steroids** in the gonads and peripheral tissue. Circulating DHEA-sulfate is the best measure of adrenal androgen excess. Some DHEA is also converted to androstenedione. Ultimately, both are converted to **testosterone** in peripheral tissues, which is converted to **5-alpha-dihydrotestosterone** (DHT), the most potent androgen.[2] Adrenal androgens do not play a major role in the adult male because the testes are the major source of testosterone. However, adrenal androgens are important in puberty for both males and females and are the main source of circulating testosterone in females. The rise in adrenal gland androgen synthesis is responsible for adrenarche, which precedes gonadarche.
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Catecholamines
Adrenal catecholamines, epinephrine, and norepinephrine are involved in executing the fight-or-flight response of the sympathetic nervous system. They increase blood pressure via alpha-1 receptors on vascular smooth muscle. They help increase serum glucose by activating glycogenolysis and increasing glucagon secretion via beta-2 receptors and decreasing insulin secretion via alpha-2 receptors.[
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Suspected Testing for Adrenal Issues
For example, **if Cushing syndrome is suspected**, then evidence of hypercortisolemia is sought. This can be achieved by measurement of evening plasma cortisol and or salivary cortisol, and a 24-hour urine free cortisol. Also useful are plasma ACTH levels to identify the site of the lesion and the cortisol responses to dexamethasone suppression as detailed recently. **If Addison disease (primary adrenal insufficiency) is suspected**, then one can assess the cortisol response to synthetic ACTH (short synacthen test) , and if peak levels are less than 18 ug/dl then the diagnosis is confirmed, and an elevated ACTH is adjunctive evidence. **If primary hyperaldosteronism** is suspected since the patient has hypokalemic alkalosis and hypertension, then the measurement of the plasma aldosterone (PAC) coupled with the aldosterone to renin ratio (ARR) is the most useful screening tests. PAC is generally greater than 15 ng/dl and the ARR greater than 30.[10] **If a pheochromocytoma is suspected**, measurement of plasma or urine metanephrines is the test of choice. In the commonest form of adreno-genital syndrome due to a **deficiency of 21-hydroxylase** resulting in glucocorticoid and mineralocorticoid deficiency and ambiguous genitalia in females and iso-sexual precocity in males, the most useful test is 17-OH-progesterone levels.
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Fick's Equation
Law governing diffusion of gases from high to low concentration gradient Rate of diffusion = dn/dt x D X A X dc/dx where, n = quantity, t = time, d = diffusion D = diffusion coefficient (cm2/second) A = surface area dc = diffusion in partial pressures of gas dx = thickness of barrier
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Poiseuille's Equation
Resistance = 8x Length x Viscosity of Gas ------------------------------------------ pi x radius rest to 4 describes resistance of laminar airflow indicates that resistance increases dramatically as airways narrows (low radius)
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**Laplace's Law of Gas** pressures and surface tension inside a bubble
**P =2 x Surface Tension / Radius** inside a bubble The law explains that as the radius of a tube or sphere increases, the pressure gradient across the wall decreases. It also states that as the surface tension increases, the pressure gradient across the wall also increases.
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Soluble Transferrin Receptors
Most abundant on nucleated RBCs in bone marrow, helps with Iron deficiency assessment The **sTfR level is elevated in IDA** but is unaffected by inflammation and, therefore, has the potential to better differentiate IDA from Anemia of chronic disease (ACD). Adjunct diagnostic criteria for IDA: - microcytosis with an MCV <80fL, - the sTfR of >55.0nmol/L and - sTfR-ferritin index of>1.4.
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Hepcidin
**Hepcidin is an iron-regulating peptide hormone** made in the liver. It controls the delivery of iron to blood plasma from intestinal cells absorbing iron, from erythrocyte-recycling macrophages, and from iron-storing hepatocytes. During conditions in which the **hepcidin level is abnormally high**, such as inflammation, serum iron falls due to iron trapping within macrophages and liver cells and decreased gut iron absorption. This typically leads to anemia due to an inadequate amount of serum iron being available for developing red blood cells. **When the hepcidin level is abnormally low** such as in hemochromatosis, **iron overload occurs** due to increased ferroportin mediated iron efflux from storage and increased gut iron absorption.
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Median Arcuate Ligament
The **median arcuate ligament** is a ligament formed at the **base of the diaphragm** where the left and right diaphragmatic crura join near the 12th thoracic vertebra. This fibrous arch forms the anterior aspect of the aortic hiatus, through which the **aorta, thoracic duct, and azygos vein** pass. The median arcuate ligament usually comes into contact with the aorta above the branch point of the celiac artery. However, in up to one quarter of normal individuals, the median arcuate ligament passes in front of the celiac artery, compressing the celiac artery and nearby structures such as the celiac ganglia. In some of these individuals, this compression is pathologic and leads to the **median arcuate ligament syndrome**
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Functions of branches of **Facial nerve**
TeZ BuMaC **Temporal branch**: contract the forehead and elevate eye brow **Zygomatic branch**: open and shut eyes **Buccal branch**: smiling **Mandibular branch**: frowning **Cervical branch**: contract the platysma muscle
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Spinal cord section
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Physiological changes in Pregnancy
Peripheral vasodilation Increased CO & Heart rate Increase circulatory volume Increased MV/ tidal volume Increased O2 consumption
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Inverse Square law for Magnates
**Inverse Square Law:** The most common relationship between magnetic force and distance is the inverse square law. This means if you double the distance, the force weakens to one-quarter (1/2 squared). If you triple the distance, the force becomes one-ninth (1/3 squared), and so on.
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Cerebral perfusion pressure, CPP
CPP = MAP - ICP Normal ICP, 5-15 mmHg ICP correlates with CVP Cerebral blood flow autoregulation is lost below CPP of 40 mmHg
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Branches of Abdominal Aorta
**Paired Branches**: 1. Inferior Phrenic Arteries: Supply the diaphragm. 2. Middle Adrenal Arteries: Supply the adrenal glands. 3. Renal Arteries: Supply the kidneys. 4. Gonadal Arteries: Supply the ovaries in females (ovarian arteries) and testes in males (testicular arteries). 5. Lumbar Arteries: Supply the muscles and spinal cord in the lumbar region. **Unpaired Branches**: 1. Celiac Artery: divides into the common hepatic artery, splenic artery, and left gastric artery, supplying the stomach, liver, spleen, and pancreas. 2. Superior Mesenteric Artery: Supplies the small intestine, pancreas, and parts of the large intestine. 3. Inferior Mesenteric Artery: Supplies the remaining parts of the large intestine. 4. Median Sacral Artery: Supplies the sacrum and coccyx. **Terminal Branches**: Common Iliac Arteries: Each common iliac artery then divides into the internal and external iliac arteries. The internal iliac artery supplies the pelvic organs and perineum, while the external iliac artery continues into the lower limb as the femoral artery.
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Liver Segments
**Segment 1 (Caudate Lobe)**: Located posteriorly, between the fissure for the ligamentum venosum and the inferior vena cava (IVC). **Left Lobe**: Further divided into medial (S4) and lateral segments (S2 and S3). Segment 2: Left lateral superior. Segment 3: Left lateral inferior. Segment 4: Medial segment, further divided into superior (4a) and inferior (4b) parts. **Right Lobe**: Divided into anterior (S5 and S8) and posterior segments (S6 and S7). Segment 5: Right anteroinferior. Segment 6: Right posteroinferior. Segment 7: Right posterosuperior. Segment 8: Right anterosuperior.
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Positive Feedback Loop: Example
Each change triggers another which cycles and can go on forever if no limiting mechanism. 1. Fetus pressure on cervix send feed back signals to brain = 2. Oxytocin is released from hypothalamus = 3. Oxytocin increases forces of uterine contractions = 3. This exerts more pressure on cervix = 4. More oxytocin is releases increasing further uterine contractions. This goes on until baby is delivered and pressure on cervix is released.
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PH (Potential of Hydrogen)
Indicates amount of free H ions in a solution. Water has 10(-7) mole/Lit of free H ions and represent neutral solution. More H than this makes it acidic and PH drops. Less H than this makes it basic and pH increases. Difference between pH of 6.8 and 8 (range for sustaining life) is only 148 nmols (1.48 x 10(-7) moles/Lit) of H ions.
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Biological buffers
Conjugate pairs: Acid = H + Base A strong acid completely dissociates in a solution. **Law of mass action**: reactions depends on the concentration if the chemicals involved ie if H is added, more acid is formed. K = [H] [base]/ [acid] Where, K = dissociation constant pK = -log10K 1. **CO2-HCO3 Buffer** - removes H as co2 through lungs by formula: CO2 + H2O = H2CO3 = H + HCO3 Capacity 18 mmols of H/Lit 2. **Hemoglobin buffer**: large capacity - 8 mmols of H /lit CO2 + Hb = HbCOO + H 3. **Phosphate buffer**: Humans secret PO4 in urine which can absorb H secreted in urine. Inside body H is only absorbed by buffers but not removed hence its excretion in urine is important. H2PO4 = HPO4 + H
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Henderson - Hasselbalch Equation
Expresses the relationship between H and the concentration of the buffer pair. pH = pK + log10[base]/ [acid] **For HCO3/CO2 system**: pH = pK + log10[HCO3]/ [H2CO3] ie pH = pK + log10[HCO3] /[CO2] As most CO2 is converted to H2CO3 Normal ratio of HCO3:CO2 is 20:1 in ECF Hence pH = 6.1 + log10[20/1] = 7.4 Where, HCO3 = 24 mmols and [CO2] = 1.2 mmols/Lit
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Buffering H in urine
Hydrogen in urine is buffered by 2 mechanisms: 1. H combines with Na and Phosphate to form NaH2PO4 which is then excreted 2. H combines with ammonia(NH3) synthesised by tubule cells from glutamine - to form ammonium (NH4) which is then excreted. This ensures that pH of ursine doesnot fall below 4.5 and H does not diffuse back to body.
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Atomic structure
Atom has central nucleus containing protons and neutrons surrounded by cloud of electrons. **Atomic number**: number of protons in atom, example- Carbon has 6 proton and hence its atomic number is 6. **Atomic mass**: total of protons and neutrons together in an atom and is variable, example - Carbon has 6 protons + 6/7/8 neutrons and hence different isotopes with atomic mass 12 for C-12, 13 for C-13 etc **Electrons** are in fixed shells and innermost shell can carry only 2, next shell can contain 8 and third can hold upto 18. These numbers are fixed.
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Chemical bonds
1. **Ionic bonds**: between atoms, they dissolve in water or solution as charged particles, NaCl become Na(cations, +ve) and Cl (anions, -ve) 2. **Covalent bonds**: sharing of electrons between atoms, maximum possible 3 pairs of them, to stabilize themselves. They can be - **single, double or triple** and more stronger. 3. **Stereoisomers**: Stereoisomers of carbon are molecules with the same molecular formula and connectivity but differ in the three-dimensional arrangement of atoms around carbon atoms. The main types are enantiomers (mirror images) and diastereomers (non-mirror stereoisomers, including cis/trans and E/Z forms). They rotate polarised light in either a clockwise (dextro-rotatory) or anticlockwise (Levo-rotatory) 4. **Carbon=Carbon double bonds** Between carbon atoms, atoms can be **cis** ie same side of double bonds or **trans** ie opposite sides of double bond. Some fatty acids, commercial ones are trans type and raise blood cholesterol.
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Polar and non polar covalent bonds
Electrons are shared between atoms but not equally - they ie electrons tend to lean to one atom more, Example 1.- in H2O - shared electrons tends to be closer to Oxygen making them partially negative and away from hydrogen making it partially positive. Thus it has two charge molecules known as **dipoles** and such a bond is **polar covalent** bond. Example 2: non polar bonds has equally shared electrons with no charged atoms, such as methane (CH4)
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Hydrogen bond
A weak type of bond Partial positive H+ atom attracts to partial negative atom such as oxygen or nitrogen and forms this bond Can be disrupted easily by heat/acidity example as in ice - easily become water in response to heat
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Compounds within body
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Macromolecules in body
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Amino acids in Human proteins
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Amino acid structure
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Glycine Structure Non polar aliphatic
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Alanine structure Non polar aliphatic
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Valine structure Non polar aliphatic
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Leucine structure Non polar aliphatic
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Isoleucine structure Non polar aliphatic
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Phenyl alanine and Tyrosine Non polar aliphatic
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Tryptophan structure Non polar aromatic
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Serine structure Polar uncharged
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Threonine structure Polar uncharged
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Asparagine structure Polar uncharged
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Glutamine structure Polar uncharged
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Glutamic acid structure Polar negatively charged
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Aspartic acid structure Polar negatively charged
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Lysine structure Polar positively charged
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Arginine structure Polar positively charged
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Histidine structure Polar positively charged
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Cysteine structure Sulphur containing
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Methionine structure Sulphur containing
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Proline structure Amino type
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Non Polar Amino Acids
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All amino acids, 20
Glycine (non polar aliphatic) Alanine Valine Leucine Isoleucine Tyrosine (non polar aromatic) Phenyl alanine Tryptophan Serine (polar uncharged) Threonine Asparagine Glutamine Aspartic acid (Polar negative charged) Glutamic acid Histidine (Polar +ve charged) Lysine Arginine Cysteine (sulphur containing) Methionine Proline (Imino)
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Protein modifications
1. **Acetylation**: addition of acetyl (CH3CO) to N-terminal, increases lifespan 2. **Glycosylation**: A. Glycoproteins - addition of carbohydrates to serine/Threonine to OH group known as O-glycosylation via amide group to asparagine (N-glycosylation) or hydroxylysine amino acid side chains, only possible with these. B. Proteoglycans: core protein linked to large chains of carbohydrates 3. Lipid modifications: fatty acids attached to proteins 4. Phosphorylation: Additional of PO4 group by kinases or their removal by phosphatases
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Classes of Enzymes
1. **Oxio-reductases**: oxidation & reduction reactions, often with Coenzymes as NAD, Ex- dehydrogenase, Oxidase, peroxidase, reductase 2. **Transferases**: Transfer of amino, carboxyl, acyl, carbonyl, methyl, phosphate groups from one molecule to other, Ex- transaminase, transcarboxylase 3. **Hydrolases**: cleave bond between carbon & another atom by inserting water, Ex- esterase, petite, amylase, phosphatase, pepsin, trypsin 4. **Lyases**: breaks carbon-carbon, carbon-sulphur, carbon-nitrogen but not peptide bonds, Ex- decarboxylase, aldolase 5. **Isomerases**: Racemisation of optical or geometric isomers Ex- Epimerase, mutate 6. **Ligases**: formation of bonds between carbon-oxygen, sulphur, nitrogen, etc often hydrolysing ATP to provide required energy Ex- synthetase, carboxylate
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Cyanogenic glycosides
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Treating cyanide poisoning
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Mitochondrial poisons: Complex 1 inhibitors
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Mitochondrial Poisons: Complex 2 & 3 inhibitors
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Mitochondrial inhibitors: Complex IV inhibitors
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Mitochondrial poisons: Complex V inhibitors
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Mitochondrial poisons: Uncouples
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Mitochondrial poisons: DNA synthesis blockers Protein synthesis blockers
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Mitochondrial poisons: Blockers of pyruvate metabolism
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Triose sugars: Contains 3 carbon (CH2O)n Contained either Aldehyde attached to C1 or ketone as side group to C2 Virtually all sugars in nature are D-isomers
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Glucose molecule, Hexose, C6H12O6
Exists in 4 forms, all freely convertible in water, 1. Straight chain: aldehyde at C1, <1% 2. Alfa-D-Glucose, a pyramids ring, C1 attached to C5 through O, 3. Beta-D-Glucose, alfa beta are anomers and has H-OH attachment differences to C 4. D-Glucofuranose: C1 attached to C4
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Other Hexose sugars (6 carbon)
**Mannose**: an Aldose ie aldehyde side chain, tends to form pyranose rings ie 5 carbon with Oxygen, only difference with glucose, H-OH bind at C2 is reverse **Galactose**: also an aldose, tends to form pyranose rings, different from glucose by only H-OH bond at C4 reverse **Fructose**: a ketose, forms both furanose & pyranose rings
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Pentose sugars (5 Carbon)
**D-Ribose**: H-OH at C2 and **Deoxyribose** l: H-H at C2
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Other simple sugars
**Glucosamine** - amino groups replacing OH group in glucose at C2 **Galactosamine** - amino group replacing OH groups at C2 in galactose
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Disaccharides: These are two monomers joined together (ie glucose+glucose etc)
**Sucrose**: alfa-Glucose + b-Fructose **Lactose**: b-Galactose + b-Glucose **Maltose**: alfa-Glucose A + b-Glucose **Isomaltose**: alfa-Glucose + b-Glucose
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Polysaccharides
**Starches:** polymers of glucose, such as - amylose, amylopectins **non-Starches**: **Cellulose**: unbranches polymers of glucose with beta 1-4 linkage **Glycogen**: large glucose polymer Branching at every 10th glucose molecule (instead 13th as in amylopectin)
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Glycerol: Part of Triacyl-glycerol ie Triglycerides
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Triacylglycerol (also known as Triglycerides = Fatty acid + Glycerol)
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Fatty acids
Chains of carbon and hydrogen like CH2-CH2-CH2 with CH3 group at one end and COOH at other end. They can be: **Saturated** - all carbon single bonded **Mono-Un-Saturated** - one carbon has double bond **Polyunsaturated** - more than one carbon has double bond They all have one end CH3 and other end COOH
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Cis and Trans carbon bonds
Cis means next carbon is present on same side of double C=C bond Trans means next carbon atom is present on other side of C=C double bond Trans means
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Naming of fatty acids: Can be in various way Examples below
**Palmitic acid** also named as 1. CH3(CH2)14 COOH 2. n-hexa-decanoic acid 3. C16:O means has 16 carbon & no double bonds Another example: **Arachidonic acid** 1. Cis-5,8,11,14-eicosatetranoic acid 2. C20:4 w-6 (indicates position of first C=C double bond)
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Progesterone, Estrogen synthesis
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Vitamin D pathway
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Cortisol synthesis pathway
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Aldosterone synthesis
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Bile acid synthesis
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Eicosanoids: Locally acting hormones derived from FAcids &
1. Prostaglandins 2. Thromboxanes/Prostanoids 3. Leucotriens **Arachidonic acid** (Eicosa-tetra-enoic acid) is one of the FA incorporated into membrane phospholipids by enzyme **Phospholipase A2** **Eicosa-pentanoic acid** is another FA which has 3 double bonds and one of bond is at C17 which is 3 carbon away from omega carbon hence the name omega-3 FA
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Nucleotides Ribose + Phosphate + base
1. Sugar is ribose or deoxyribose (pentoses) 2. Phosphate: PO4 3. Bases are Purine or Pyrimidines **Purines**: contains 2 rings & are Adenine and Guanine **Pyrimidines** are single rings and are Cytosine, Thymine, Uracil
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Adenine, A purine, has double ring
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Guanine, a purine, has double ring
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Cytosine, A Pyrimidine, has single ring
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Thymine, A pyrimidine, has single ring
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Uracil, A pyrimidine, has single ring
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Nucleo**side** phosphates
Nucleosides are nucleotides without phosphate group ie has only ribose and base, example - ATP AMP breaks down & releases 7.3 kcal/mol but can be upto 50 kj/12kcal. 1 glucose molecule generates 36-38 ATP ie energy transfer of 1130 KJ, 270 kcal/mol. This energy is used for other cellular processes.
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ATP
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A-T-G-C pairing
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Barr body or X chromatin
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Lysosomal storage disease: Tay Sach’s disease
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Proteosomes
These are like lysosomes - large complexes of proteins arranged in 4 rings around a central core. Proteins to be degraded are labelled with multiple copies of protein called **Ubiquitin**. Only proteins labelled with ubiquitin are forwarded to central core where they are degraded into smaller peptides.
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Tau protein
Microtubule associated protein (MAP) Normally present Accumulation leads to formation of **neurofibrillary tangles** present in Alzheimer’s disease and hallmark cause.
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Cyto-skeletal elements
These are 1. Micro filaments, smallest, 7 nm, made of actin 2. Intermediate Filaments, 10 nm Forms rope like structures 3. Microtubules - has tubulin fibres made of alternate alfa and beta tubulins
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ECF vs ICF composition
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Complementary **DNA** and **RNA** strands
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Hyperchloremic acidosis mechanism
**The short version** Hyperchloremic acidosis happens because adding chloride forces the body to give up bicarbonate, lowering the strong base in plasma and shifting pH toward acidity. **The Core Mechanism: Electrically Neutral Plasma** Plasma must remain electroneutral: [Na+] + [K+] +… = [Cl-] + [HCO3-] + … When chloride rises, the body compensates by lowering bicarbonate to maintain this balance. Less bicarbonate → less buffering capacity → metabolic acidosis. This is the classical “anion exchange” explanation. --- The Deeper, More Modern Explanation: *Stewart’s Strong Ion Theory* pH is determined by three independent variables: • Strong ion difference (SID) • Total weak acids • PCO2 *For plasma:* {SID} = [{Na}^+] - [{Cl}^-] A normal SID is around 38–42. **What hyperchloremia does** When chloride rises disproportionately: {SID decreases} A lower SID means the plasma has more strong anions relative to strong cations, which forces water to dissociate in a way that increases ([{H}^+]). This is a physicochemical inevitability, not a compensatory process. So in Stewart terms: • ↓ SID → ↑ H\(^+\) → acidosis This explanation doesn’t rely on bicarbonate as a causal agent; instead, bicarbonate falls because pH changes. --- **Why saline (0.9% NaCl) is the classic culprit** Normal saline has: • Na⁺ = 154 • Cl⁻ = 154 This gives an SID of 0, far below plasma’s ~40. Infusing it drags the plasma SID downward, producing hyperchloremic metabolic acidosis. This is why balanced crystalloids (e.g., lactated Ringer’s, Plasma‑Lyte) are preferred in many clinical settings.
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MIBG scans
MIBG scanning is most useful for tumors that originate from chromaffin or sympathetic nervous system cells, including: **Most common uses** • Neuroblastoma (especially in children) • Pheochromocytoma • Paraganglioma • Medullary thyroid carcinoma • Carcinoid / other neuroendocrine tumors Cleveland Cl... **Additional uses:** • Cardiac sympathetic imaging (heart failure, cardiomyopathy) • Differentiating Parkinson’s disease from similar disorders (because Parkinson’s damages cardiac sympathetic nerves) scienceinsig...