Clinical Sciences Flashcards
Which Hormones Produced where in the Adrenals ?
GFR ACD
Glomerulosa = Aldosterone
Fasciculata = Cortisol
Reticularis = DHEA
Action of the RAAS system ?
Vasoconstriction of the Efferent Arteriole
Vasoconstriction of
Vascular Smooth Muscle
Aldosterone and ADH release
Stimulate PCT Na+/H+ Exchanger
HLA and Disease Associations
HLA A3
Hemochromatosis
HLA B51
Bechet Disease
HLA B27
HLA-DQ2/DQ8
Celiac
HLA-DR2
Narcolepsy
Good Pasture
HLA-DR3
Sjogren
Dermatitis Herpetiform
Primary Biliary Cirrhosis
HLA-DR4
T1DM , RA (DRB1 Gene)
Niacin B3 Deficiency Mnemonic ?
4D’s
Dermatitis
Dementia
Diahorrea
Death
Niacin Deficiency Seen in which Diseases ?
Carcinoid Syndrome - Incrw
Hartnups Disease - Inability to absorb Niacin
Which Chromosome is p53 and HLA located
17p and 6
Li Fraumeni Autosomal Dominant or Recessive ?
Autosomal Dominant
Commonest Cause of Down Syndrome - Cytogenetics Wise
Non Disjunction
Robertsonian Translocation
Mosaicism
Which Tumor Suppressor Gene for Melanoma ?
Burkitt’s ?
Neuroblastoma ?
Multiple tumor suppressor 1 (MTS-1, p16)
c-myc
n-myc
Whats the Equations for
- Systemic Vascular Resistance
- Ejection Fraction
- MAP/CO
- (LV Systolic Volume/End Diastolic Volume) x 100%
Factors that increase Pulse Pressure ?
Decreased Aortic Compliance
Increased Stroke Volume
Alkapturia
- Inheritance
- Pathophysiology
- Investigations
- Treatment
Read Notes
Autosomal Dominant Pathology Mnemonic ?
BOATMAN - CHF
Brugada Syndrome
Osteogenesis Imperfecta
Achondroplasia
Tuberous Sclerosis
Marfan Syndrome / Myoclonic Dystrophy (DMPK Gene Chromosome 19)
AIP/ADPKD
Neurofibromatosis
CMTD
Hereditary Spherocytosis & Hereditary Hemorrhagic Telangiectasia (HHT)
Huntington (Chromosome 4)
HNPCC
Hypokalemic Periodic Paralysis (CACNA1S Gene)
Familial Hypercholesteremia
FAP
Autosomal recessive conditions are ‘metabolic’ - exceptions: inherited ataxias
Autosomal dominant conditions are ‘structural’ - exceptions: Gilbert’s, hyperlipidemia type II
Mnemonic for X linked
DAGOBAH
DMD
Aldrich Syndrome
G6PD
Ocular Albinism
Beker’s Muscular Dystrophy
Agammaglobinemia
Hunters Syndrome
A - androgen insensitivity syndrome
B - Becker/Duchenne
C - Colour blindness
D - Diabetes insipidus (nephrogenic)
E - eyes (retinitis pigmentosa)
F - Fabry
G - G6PD deficiency
H - haemophilia A/B, Hunter’s
Autosomal recessive conditions are ‘metabolic’ - exceptions: inherited ataxias
Autosomal dominant conditions are ‘structural’ - exceptions: Gilbert’s, hyperlipidaemia type II
Leber Optic Neuropathy ?
- Pathophysiology
- Features
- NADH-CoQ Oxidoreductase (NADH Dehydrogenase) Defect
at ETC Complex 1 - Central Expanding Scotoma –> Blindness
MELAS Syndrome
- Mnemonic
- Features
Mitochondrial Encephalopathy
Lactic Acidosis in CSF
Stroke
Atypical Stroke crossing vascular territories in <40 + Lactic Acidosis in CSF = THINK MELAS
MERRF
- Mnemonic
- Features
Myoclonus
Epilepsy
Red Ragged Fibers
Light - Red Ragged Fibers
Electron - Mitochondrial Crystalline Inclusion
Kearns-Sayre Syndrome (Oculocraniosomatic Disorder)
- Features
- Investigations
Ophthalmoplegia –> Diplopia
Ptosis
Retinitis Pigmentosa
< 20y/o
Conduction Defects
Reg Ragged Fibres with irregular Contours
Reg Mitochondria
Mitochondrial Diseases ?
MELAS
MERRF
Lebers Optic Atrophy
Kearns-Sayre Syndrome
Fabry’s Disease Mnemonic FABRY ?
FABRY
(Lack of breakdown in globotriaosylceramide due to Alpha galactosidase A Deficiency)
F - Fail to sweat
A - Alpha galactosidase A Deficiency , Angiokeratoma and cornea verticillate
B - Burning pain in Hands and Feet
R - Nephrotic Renal failure
Y - Y type - common in male - therefore, X linked recessive
What is the Right and Left Kidney Directly in Contact with ?
Right Kidney
1. Right suprarenal gland
2. Duodenum
3. Colon
Left Kidney
1. Left suprarenal gland
2. Pancreas
3. Colon
Interleukin 1 Released by ?
Released by Macrophages /Monocytes
IL2 Functions ?
Induce PAF, Prostacyclin and Nitric Oxide = VASODILATION
Increase Selectin in Vascular Wall = Allowing Rolling of Leukocytes
IL2 (+IL6 and TNF Alpha) = Induce Fever
Nonsense (Premature Stop codon)
Silent (Un-noticed)
Missense (Point Mutation making the Protein Non Functional)
Cardiac Action Potential Stages
Phase 0 - ‘Summit’ -
* RAPID NA INFLUX*
RAPID DEPOLARISATION
Phase 1 - ‘Plummit’ - Potassium out - Repolarisation
Phase 2 - ‘Continue’ -
** SLOW Calcium in ** - Plateau
Phase 3 - ‘Plummit’ - Potassium out - Repolarisation
Which is the Fastest Conduction ?
- AV
- SA
- Purkiinje
Purkinje has the largest diameter
How does NO lead to Vasodilatation ?
Read the Note
What are the functions of NO ?
Vasodilatation AND Inhibit Platelet Aggregation
Hyperacute
Acute
Chronic Rejection (>6 months)
B cells in Hyperacute
Tcells TH1 / TH2 in Acute and Chronic
Motor Supply of Ulnar Nerve Mnemonic (MAFIA)
CLAW HAND
Medial Lumbricals
Adductor Pollicis (Pincer Grip)
First Dorsal Interossei
Interossei
Abductor Digiti Minimi + Flexor Digiti Minimi (Hypothenar)
Motor supply of Radial Nerve Mnemonic (BESTS)
Bracioradialis
Extensors of the Wrist
Supinator
Triceps
Loss of Sensation over anatomical Snuff Box
Motor supply of Median Nerve Mnemonic (LOAF)
Lateral Two Lumbicals
Opponens Pollicis
Abductor Pollicis Brevis
Flexor Pollicis Brevis
Branches of Ulnar Nerve 5 and innervations
Deep Branch
X linked Recessive Inheritance % Question Facts
Every Girl Born to Affected Dad is a Carrier for X linked Recessive Pathologies
Affected males can only have unaffected sons and carrier daughters.
Each male child of a heterozygous female carrier has a 50% chance of being affected whilst each female child of a heterozygous female carrier has a 50% chance of being a carrier.
Tay Sachs
Gauchers
Neil Pickmann
Galactosemia
Which Enzymes are Deficient ?
Deficiency of Sphingomyelinase = Niemann-Pick disease
(hepatosplenomegaly, developmental delay, and neurological decline)
Deficiency of galactose-1-phosphate uridyltransferase = Galactosemia
Deficiency of hexosaminidase A = Tay-Sachs disease (developmental regression and a cherry-red spot on the retina WITHOUT ORGANOMEGALY)
Deficiency of beta-glucosidase = Gaucher disease (hepatosplenomegaly, bone pain, and pancytopenia)
Vitamin C Deficiency Pathophysiology ?
Vitamin C needed for Hydroxylation of Proline and Lysine in the synthesis of collagen
Vitamin C Functions (NICE)
N- Norepinephrine synthesis cofactor
I- Iron absorption facilitation
C- Collagen synthesis
E- E(A)nti-oxidant
Vitamin C Deficiency Features
Features of Vitamin C Deficiency (M.O.L.D.)
M-Malaise
O-Oral issues (gingivitis, loose teeth, bleeding gums)
L-Loss of blood (haematuria, epistaxis)
D-Delayed wound healing
Non REM 1 associated with ?
Non REM 2
NON REM 3 associated with ?
REM associated with ?
Non REM 1 - Hypnic Jerks
Non REM 2
NON REM 3 - Nocturnal Eneuris, Sleep Walking
REM - Dreaming
What Brain Waves at Each Step of Sleep ?
The Sleep Doctors Brain
Theta
Spindle Spindles K+
Delta
Beta
Function of
1. RER
2. SER
3. Lysosomes
4. Proteasome
5. Peroxisome
6. Where does RNA Splicing Happen ?
7. Golgi adds what to Proteins to Traffick them into Lysosome ?
1.
Translate and Pack Proteins
Lysosomal Production
N-linked Glycosylation
- Steroid and Lipid Synthesis
- Breakdown Large molecules eg Polysaccharides
- Breakdown Proteins tagged with Ubiquitin
- Breakdown very long chain fatty acids and AA into H202
- Nucleus
- Mannose - 6 - Phosphate
Which Pathologies do we use Interferon Alpha ?
He Knit My Hair
Hep B/C
Karposi Sarcoma
Metastatic Renal Cancer
Hairy Cell Leukemia
When do we use Interferon Beta and Gamma ?
alpha = virus + cancer
Beta = brain (MS)
Gamma = Granuloma and Osteopetrosis
Troponins and where they bind to
TIC TAC
Trop T - Tropomyosin
Trop I - Actin
Trop C - Calcium
Layers of the Skin
Come (Corneum)
Let’s (Lucidum) - Thick Skin (palms and soles) , Cotains Eledin derived from Keratinohyalin
Get (Granulosum) - Links with Neighbors
Sun (Spinosum) - THICKEST LAYER , Squamous Cells begin Ketatin Synthesis
Burnt (Basale) or Germs (Germinativum) - Columnar Epithelial Cells , Melanocytes , Keratinocytes
Drugs that interfere with Folate metabolism ?
DHF reductase inhibitors - Trimethoprim and Methotrexate
5FU - Thymidylate Synthase Inhibitor
Look at Medicosis Folate Synthesis Diagram which is in the Homocystinuria Video / Note
TH1 release what Cytokines ?
Interferon A
TH2 release what kind of cytokines ?
- SLE , HSP ?
- C3
- C5
- C5-C9
- C1q, C1rs, C2, C4 deficiency
- Recurrent Bacterial
- Predisposes to Leiner disease - Recurrent Diahorrea , Wasting and Seborrheic Dermatitis
- MAC and Neisseria Meningitis
Renal Physiology Facts
Thin Ascending Limb - Water Out No Salt in
Thin Ascending Limb -
No Water Little Salt out
Thick Ascending Limb
Lots of Salt Out No Water Out
So the surrounding gets more salty which means the Tubular fluid within is Comparatively HYPO-Osmolar to the Intersitium
Which cells release Surfactant ?
Type 1 Pneumocytes (Cuboidal)
Type 2 Pneumocytes develop after X weeks until Y weeks. Whats X and Y ?
24 to 35 weeks
CAA Guidance for Flying Rules
- PCI
- CABG
- Uncomplicated MI
- Complicated MI
- Unstable Angina
- Pregnancy
- Laparoscopic Surgery ‘
- Colonoscopy
- Abdominal Open Surgery
- 3 days
- 10-14 days
- 7-10 days
- 4-6 weeks
- DO NOT FLY
- No Flying after After 36 Weeks Singleton OR After 32 weeks Multiple Pregnancy
- 24 Hours
- 24 Hours
- 10 days
Clinically how long does it take for Vitamin K to reverse the effects of Wafarinization
4 hours
Functions of
- IgA
- IgE
- IgD
- IgM
5.IgG
- Breast Milk , Mucosal Protection
Most Commonly produced Ig in the body - Synthesized by Plasma Cells
Least Abundant - Activation of B cells
- First to be release when infection and found in Anti-A/B antibodies
- Most abundant in serum
Least Abundant Ig in Blood ?
IgE
Which Ig is a Pentamer ?
IgM
Conditions which are X linked Dominant Inheritance ?
Rhett Syndrome
Vitamin D Resistance Rickets
Alports Syndrome
Which Vitamin Deficiency Causes Angular Chelitis ?
B3 Riboflavin
How does Folate Deficiency Present as ?
Mouth Ulcers
Forgetfulness
Sore Tongue
How does Biotin Deficiency Present ?
Alopecia
Scaly erythematous dermatitis located around body orifices
Hearing and Vision
Whats is
1.FISH used for
2. PCR
3. Western Blot
- Mutations with Chromosome (LOOKING FOR THE MUTATION)
- Amplify –> YOU KNOW THE MUTATION ALREAY
- Specific Proteins
Statistics READ NOTE
True but Rejected
is it T1 or T2 Error ?
Type 1
Which Types of RTA increase risk of Nephrolithiasis?
Types 1 and 3 increase risk of stone formation (types 2 and 4 do not)
What does Golgi Apparatus add to Traffick Proteins into Lysosomes ?
Golgi adds mannose-6-phosphate to proteins for trafficking to lysosomes
Most Commonest Renal Abnormality in Turners Syndrome ?
Horseshoe Kidney
Collagen Types and associated Pathologies
Type I: BONE - Osteogenesis Imperfecta
Type II: carTWOlage - Chondrodysplasia
Type III: ArTHREE (Artery) - Vascular type EDS
Type IV: Under the floor (basement membrane) - Thinning and splitting of GBS causing Alport Syndrome
Typr V - Ehler Danlos
Which Oncogene is associated with What Pathology ?
- Burkitts
- Neuroblastoma
- Follicular Lymphoma
- MEN 2 and 3
- Pancreatic
- Breast and Ovarian
- c-MYC
- n-MYC
- BLC-2
- RET
- RAS
- erb-B2 (HER2/neu)
Leptin
- How does it Suppress appetite 2 Pathways
Ghrelin
1. Released by ?
Leptin binds to ARCUATE nucleus of Hypothalamus -.> Release proopiomelanocortin (POMC) –> Release Alpha MSH –> Bind to melanocortin-4 receptors (MC4R) —> Suppress Appetite
AND
inhibition of orexigenic (appetite-stimulating) neuropeptide Y (NPY) and agouti-related peptide (AgRP) neurons.
Grelin released by P/D1 at the Fundus of the Stomach and Epsilon Cells at the Pancreas
47XXY
47XYY
Kline Felters (Tall, Small Testis with Azoospermia, Gynecomastia)
Jacobs Syndrome (Tall)
Down syndrome How to Calculate the Risk for the Age using a formula ?
1/1,000 at 30 years then divide by 3 for every 5 years
Endothelin MOA
Endothelin (Prodrug) converted to ET-1 by Endothelin Converting Enzyme
Inhibit NO and Prostacyclin
CAUSING PULMONARY VASOCONTRICTION
In P value we always assume Null Hypothesis is TRUE to be able to observe our finding due to chance
Ligand Gated Channels ?
Tyrosine kinase receptors?
Guanylate cyclase receptors
G protein-coupled receptors
Ligand Gated Channels ?
GABA A/C
Nicotinic Ach
Glutamate
Tyrosine Kinase Receptor
Tyrosine kinase:
1. insulin,
2. insulin-like growth factor (IGF),
3. epidermal growth factor (EGF)
Non-receptor tyrosine kinase: PIGG(L)ET:
- Prolactin, 2. Immunomodulators (cytokines IL-2, Il-6, IFN),
- GH,
- G-CSF,
- Erythropoietin
- Thromobopoietin
Guanylate cyclase receptors
ANP / BNP
G protein-coupled receptors
CHECK PRINTED TABLE
Control of Respiration via Central and Peripheral Chemorecptors. What are they triggered by ?
central: raised [H+] in ECF stimulates respiration
peripheral: carotid + aortic bodies, respond to raised pCO2 & [H+],
lesser extent low pO2
What is Hering-Bruer reflex?
Lung distension causes slowing of respiratory rate due to Stretch Receptors
What conditions associated with Vit B1 Deficiency
Wernicke’s encephalopathy: nystagmus, ophthalmoplegia and ataxia
Korsakoff’s syndrome: amnesia, confabulation
dry beriberi: peripheral neuropathy
wet beriberi: dilated cardiomyopathy
Virus Causing Cancers
Which Causes Which ?
Epstein-Barr virus
Burkitt’s lymphoma
Hodgkin’s lymphoma
Post transplant lymphoma
Nasopharyngeal carcinoma
Human papillomavirus 16/18
Cervical cancer
Anal cancer
Penile cancer
Vulval cancer
Oropharyngeal cancer
Human herpes virus 8 Kaposi’s sarcoma
Human T-lymphotropic virus 1
Tropical spastic paraparesis
Adult T cell leukaemia
Cardiac Manifestations of Turners Syndrome
Bicuspid Aortic Valve
Coarctation of Aorta
MOT COMMON LONG TERM HEART ISSUE = Dissection (Adulthood vs Childhood)
Turners Syndrome other Manifestations
Lymphedema in Feet as neonates
Hypothyroidism
Cystic Hygroma (diagnosed in utero)
FSH and LH elevated with Estrogen Low
Molecular Biology Techniques
SNOW DROP
South - DNA
NOrth - RNA
West - Protein (Electrophoresis that separates based on Protein weight eg -Confirmatory HIV Test)
ELISA - Antigen - Antibody Complex Detection - Initial HIV Test
Read Ulnar and Median Nerve Note and Sensations
Endothelin release triggered by ?
(G-protein linked to phospholipase C leading to calcium release)
Angiotensin II
ADH
hypoxia
mechanical shearing forces
Non-parametric:
Spearman - correlation
Chi-squared - percentage or proportion
Mann-Whitney - unpaired - ordinal, interval, ratio
Wilcoxon - paired - before/after
Function of p53
Prevents Cell Cycle Entry into S phase until DNA check and repairs complete
Function of MSH 1 /2
Function of BRCA 1 /2
Mismatch repair of single-strand DNA breaks
Repair of Double-strand DNA breaks
Drugs causing Impaired Glucose Tolerance STATIN
Steroids
Thiazides
Antipsychotics
Tacrolimus/ciclosporin
Interferon-alpha
Nicotinic acid
and BB
everything big (hydocephalus) : toxoplasmosis
everything small (microcephaly, low birth weight) : CMV
Congenital Rubella Features
Sensorineural deafness
Congenital cataracts
Congenital heart disease (e.g. patent ductus arteriosus)
Glaucoma
- Growth retardation
- Hepatosplenomegaly
- Purpuric skin lesions
- ‘Salt and pepper’ chorioretinitis
- Microphthalmia
- Cerebral palsy
Congenital CMV and TOXO Features
CMV
Cerebral calcification
Chorioretinitis
Hydrocephalus
TOXO
Low birth weight
Purpuric skin lesions
Sensorineural deafness
Microcephaly
Folate Absorbed in
Vs
Iron Absorbed in
vs
Vitamin B12
Duodenum
Jejunum
Ileum
1 SD / 2 SD / 3 SD
1 SD : 68.3
2 SD : 95.4
3 SD : 99.7
1 SD (68.3%) = 0.3
2 SD (95.4%) = 0.3 X 2 =0.6
3 SD (99.7%) = 0.3 X 3 =0.9
range = (mean+ SD) & (mean - SD)
William Syndrome
Chromosome 7 microdeletion (diagnosed via FISH)
elfin-like facies
characteristic like affect - very friendly and social
learning difficulties
short stature
transient neonatal hypercalcaemia
supravalvular aortic stenosis
Expressivity vs Penetrance
Expressivity - Severity
Penetrance - How Likely to develop
Leukotrines facts
leukotriene D4 has been identified as the SRS-A (slow reacting substance of anaphylaxis)
Downs Syndrome Most Common Cardiac Abnormality ?
Endocardial Cushion
As HIV Progresses what type of immune responses are shown ?
Reduction in CD4 count
*
Increase B2-Microglobulin (IBM) - Due to increased cell turnover
Decrease IL-2 production (DIL=DELL) } IBM & DELL
Polyclonal B-cell activation
NK cell function
delayed hypersensitivity responses
Foramens of Trigeminal Nerve
SRO Mnemonic
TRIGEMINAL NERVE (V) DIVISIONS:
OPHTHALMIC NERVE (V1) — Superior orbital fissure
MAXILLARY NERVE (V2) — Rotundum
MANDIBULAR NERVE(V3) — Ovale
Hormone secreted by the Adrenal Medulla
Adrenaline
Phases of a Trial
Remember the Mnemonic → ESAAP
0 Exploratory studies,
1 Safety - Healthy Volunteers
2a - Optimal Dosing
2b - Efficacy
3. Assessment of
effectiveness - Compare new treatment with existing
4 .Post surveillance - Long Term SE
Noonan Syndrome
Inheritance
Features
- Autosomal Dominant Chromosome 12
KARYOTYPE NORMAL !!!!!!!
Triangular Face
Factor 11 Deficiency
Pulmonary Stenosis
Ptosis
+
Turners Characteristics (webbed neck, widely-spaced nipples, short stature, pectus carinatum and excavatum)
Interferon Alpha / Beta and Gamma
Beta by FibroBlasts , MS(Brain)
Alpha by Leukocytes Antiviral
Hep B/C, Karposi Sarcoma, Hairy Cell Leukemia, Metastatic Renal Cell Cancer
Gamma by NK Cells Weaker Antiviral
Granulomatous diseases/Osteopetrosis
Achondroplasia Features ?
short limbs (rhizomelia) with shortened fingers (brachydactyly)
large head with frontal bossing and narrow foramen magnum
midface hypoplasia with a flattened nasal bridge
‘trident’ hands
lumbar lordosis
Acondroplasia Mutation ?
Fibroblast growth factor receptor 3 (FGFR-3)
Drugs to use when Breastfeeding !!
Can Use Can’t use
WHEN BREASTFEEDING !!!!
Digoxin but not Amiodarone
Warfarin but not Aspirin
Trimethoprim but not Sulpha
Levothyroxine but not carbamazole
TCA & antidepressant but not lithium
valporate and carbamazepine but not benzodiazepines
Cyclosporin. but not methotrexate
