Basic Sciences Stuff Flashcards

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. Clinicians order this laboratory test when they are concerned about iron deficiency, which can cause anemia and other problems. 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. None of this iron is directly accessible by testing the serum.

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 adreenal 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 causes Hypertension(Na gain)

Spironolactone - 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 - 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

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
tests 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

25
Q

Lung volumes, 01

A

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.

VT, Tidal volume: that volume of air moved into or out of the lungs during quiet breathing (VT indicates a subdivision of the lung; when tidal volume is precisely measured, as in gas exchange calculation, the symbol TV or VT is used.)

FRC, Functional residual capacity:
the volume in the lungs at the end-expiratory position
RV/TLC%, Residual volume expressed as percent of TLC

26
Q

Lung Volumes, 02

A

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
Q

Oxygen Index

A

calculated for premature babies

OI = (FiO2 X Mean Airway pressure) / PaO2

> 40 - consider ECMO support

28
Q

Hormones & Second Messengers

A

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
Q

Nuclear Hormones

A

Corticosteroids
Vitamin D
Retinoic Acid
Sex Steroids

30
Q

Hering Breuer Lung Inflation Reflex

A

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
Q

Bohr Effect

A

Hydrogen ions reduce Hemoglobin affinity for oxygen by altering the structure of Hb so that it binds less easily to Oxygen and is known as Bohr effect

32
Q

Haldane effect

A

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
Q

Genetic imprinting

A

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
Q

Antibody Isotypes

A

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 as 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
Q

Cryoglobulins

A

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.
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:
Monoclonal IgM cryoglobulins, causes hyperviscosity as in Waldernstrom’s
Type II:
mixed mono/ polyclonal cryoglobulins
seen with Hepatitis C, chronic infections
Type III:
Polyclonal cryoglobulins
seen in CTDs as Sjogrens, SLE

36
Q

Complement pathways

A

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
Q

Phases of Action Potential

A

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
Q

Blotting methods

A

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
Q

Agar mediums

A

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
Q

Essential Amino acids

A

PVT TIM HiLL
1. Phenyl alanine
2. Valine
3. Tryptophan

  1. Threonine
  2. Isoleucine
  3. Methionine
  4. Histidine
  5. Leucine
  6. Lysine
41
Q

Human Leucocyte Antigens

A

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
Q

Major Histocompatibility complex, MHC

A

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
Q

Phases of cell Cycle

A

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
Q

Adrenal Hormones

A

Adrenal Cortex: 3 layers
Zona GFR-Miner G A
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 produced steroid hormones synthesized from cholesterol.

Adrenal medulla produces the catecholamines, epinephrine, and norepinephrine.

45
Q

Hypothalamic-Pituitary-Adrenal Axis:

A

Hypothalamic-Pituitary-Adrenal (HPA) Axis

The 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).[1][6] 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.[6]

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
Q

Renin-Angiotensin-Aldosterone system

A

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.

47
Q

Mineralocorticoids

A

Mineralocorticoids

The mineralocorticoids, which include corticosterone, 11-deoxycorticosterone, and more importantly, 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.[9]

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.[9]

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.

48
Q

Glucocorticoids

A

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.

49
Q

Androgens

A

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.

50
Q

Catecholamines

A

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.[

51
Q

Suspected Testing for Adrenal Issues

A

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.[13] If Addison disease (primary adrenal insufficiency) is suspected, then one can assess the cortisol response to synthetic ACTH, 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.

52
Q

Fick’s Equation

A

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

53
Q

Poiseuille’s Equation

A

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)

54
Q

Laplace’s Law of Gas

A

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.

55
Q

Soluble Transferrin Receptors

A

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 were a microcytosis with an MCV <80fL, the
sTfR of >55.0nmol/L and
sTfR-ferritin index of>1.4.

56
Q

Hepcidin

A

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.