PHASE 1 Revision

1

IMMS (2)

• PHASE 1 Revision
• Akanksha Sinha
• Regina Sarbaratnam

The Peer Teaching Society is not liable for false
or misleading information
2
Aims - Overview

• METABOLISM
• (Carbohydrates, Protein, Lipid, Alcohol,
  Glycogen)
• ATP
• (ATP-ADP cycle, Glycolysis, Krebs cycle,
  Oxidative Phosphorylation)
• FATTY ACID OXIDATION/KETONES
• (Beta oxidation, Ketogenesis)
• ACID/BASE/BUFFER (Henderson-Hasselbach equation)
• OXYGEN TOXICITY (ROS, Haber-Weiss and Fenton
  reactions)
• HISTOLOGY (Stains, Epithelia)

The Peer Teaching Society is not liable for false
or misleading information
3
Metabolism

• The chemical processes that occur within a living
  organism in order to maintain life

The Peer Teaching Society is not liable for false
or misleading information
4
Metabolism
4 main energy sources Carbohydrates Starch,
fructose, sucrose, glucose, lactose Mainly come
from starchy foods and fruit. Proteins Largely
come from meat ,dairy ,pulses , fish Alcohol
typically ethanol Lipids triacylglycerols
4kcal/g 4kcal/g 7kcal/g 9kcal/g

The Peer Teaching Society is not liable for false
or misleading information
5
What happens to the excess energy intake?

• 1. Stored as triglycerides (approximately 15kg)
• 2. Stored as glycogen (approximately 200g in
  liver, 150g in muscle)
• 3. Stored as protein (approximately 6kg)

The Peer Teaching Society is not liable for false
or misleading information
6
BMR
Energy needed to stay alive at rest

• Increase BMR
• Increased body weight
• Hyperthyroidism
• Low ambient temperature
• Fever/infection
• Caffeine/stimulant intake
• Pregnancy

• Decrease BMR
• Increased age
• Being female
• Dieting/Starvation
• Hypothyroidism

The Peer Teaching Society is not liable for false
or misleading information
7
ATP
ATP Adenosine Triphosphate Structure
components Adenine, Ribose, 3 Phosphate
How does it provide Energy?
The Peer Teaching Society is not liable for false
or misleading information
8
ATP

• -The ATP molecule has two phosphoanhydride bonds.
• These are RELATIVELY WEAK bonds, hence require
  relatively less energy to break
• Overall more energy is released in forming the
  products that used to break bonds in the
  reactants

ATP
Hydrolysis
ADP
The Peer Teaching Society is not liable for false
or misleading information
9
ATP-ADP Cycle
ATP
CO2
Respiration Energy production Carbohydrate Lipid
Protein
Energy utilization Biosynthesis of
macromolecules Muscle contraction Active ion
transport Thermogenesis
ADP Pi
O2
The Peer Teaching Society is not liable for false
or misleading information
10
ATP- ways to generate ATP?

• Glycolysis
• Krebs cycle
• Oxidative phosphorylation
• Substrate level phosphorylation
• Via electron transport chain
• Beta oxidation (Discussed in fatty acid oxidation)

The Peer Teaching Society is not liable for false
or misleading information
11
Glycolysis

• Glycolysis
• Pathway of 10 steps
• Takes place in cytoplasm
• In short Glucose ?
• 2Pyruvate 2ATP 2NADH (AEROBIC)
• 2Lactate 2ATP (ANAEROBIC)

The Peer Teaching Society is not liable for false
or misleading information
12
Glycolysis
Energy Investment Phase - 2 ATP
Energy Generation Phase 4 ATP
Glycolysis generates a NET 2 ATP plus 2 NADH
The Peer Teaching Society is not liable for false
or misleading information
13
Step 1

• Facilitated diffusion of Glucose into cell
  mediated by Insulin
• Phosphorylation of Glucose by Hexokinase
• -ATP

The Peer Teaching Society is not liable for false
or misleading information
14
Step 2

• Isomerism
• G6P?F6P

The Peer Teaching Society is not liable for false
or misleading information
15
Step 3

• F6P? F1,6BP
• Via phosphofructokinase (PFK is primary regulated
  step of glycolysis responds to both cellular
  energy and hormonal regulation)
• -ATP

The Peer Teaching Society is not liable for false
or misleading information
16
Step 6-10

• 6 NADH (x2) produced
• 7 ATP (x2) produced
• 8
• 9
• 10 2Pyruvate ATP (x2) produced
• Remember all the enzymes
• Good Gracious, Father Franklin Did Go By Picking
  Pumpkins (to) Prepare Pies

Pyruvate enters the TCA cycle
The Peer Teaching Society is not liable for false
or misleading information
17
Acidosis affecting glycolysis

• PFK1 is pH dependent
• Inhibited in acidosis
• Control of glycolysis via
• Step 1
• Step 3 -key regulatory step in glycolysis

Positive regulators AMP
Negative regulators H, ATP, Citrate, hormonal
The Peer Teaching Society is not liable for false
or misleading information
18
Krebs/ TCA cycle
In Mitochondrial matrix Acetyl CoA can come from
glycolysis/ fatty acid breakdown/ amino acids
carbon skeletons
The Peer Teaching Society is not liable for false
or misleading information
19
Krebs/TCA cycle

• Inhibited by ATP, NADH, succinyl CoA
• Activated by ADP

The Peer Teaching Society is not liable for false
or misleading information
20
Electron Transport Chain

• The electron transport chain (ETC) is a process
  in which the NADH and FADH2 produced during
  glycolysis, ß-oxidation, and other catabolic
  processes are oxidized
• thus releasing energy in the form of ATP. The
  mechanism by which ATP is formed in the ETC is
  called chemiosmotic phosphorylation

The Peer Teaching Society is not liable for false
or misleading information
21
The chemiosmotic theory

• Based on the following
• -inner mitochondrial membrane is impermeable to
  protons, hence the mitochondrial matrix is a
  closed environment
• -the proton pumping of the ETC leads to the
  proton motive force which in turn provides the
  energy for ATP synthesis (Proton flow through the
  ATP synthase protein drives ATP synthesis)

The Peer Teaching Society is not liable for false
or misleading information
22
The chemiosmotic theory
The Peer Teaching Society is not liable for false
or misleading information
23
Substrate level phosphorylation

• some ATP can be made in the cytoplasm through a
  process called substrate-level phosphorylation
• With this type of phosphorylation you have an
  adenosine diphosphate (ADP), which is a unit of
  adenosine attached to two (di) phosphate groups

The Peer Teaching Society is not liable for false
or misleading information
24

• oxidative phosphorylation

• Oxidative phosphorylation is the metabolic
  pathway in which the mitochondria in cells use
  their structure, enzymes, and energy released by
  the oxidation of nutrients to reform ATP
• (involves ETC!!!)

The Peer Teaching Society is not liable for false
or misleading information
25
TOTAL ATP

• Total ATP made from one molecule of glucose
• 34 ATP
• But this is very debatable
• Some sources will say 30 or 32 ATP

The Peer Teaching Society is not liable for false
or misleading information
26
Fatty acid oxidation/ Beta oxidation

• Examples of fatty acids
• Palmitoleic acid
• Linoleic acid
• Palmitic acid

The Peer Teaching Society is not liable for false
or misleading information
27
Fatty acid oxidation/ Beta oxidation

Fatty Acid
Acetyl CoA (used in TCA/Krebs cycle)

The Peer Teaching Society is not liable for false
or misleading information
28
Fatty acid oxidation/ Beta oxidation

ATP
PPi
Fatty Acid
Acyl adenylate

The Peer Teaching Society is not liable for false
or misleading information
29
Fatty acid oxidation/ Beta oxidation
CoA
AMP
Acyl adenylate
Acyl CoA
Acyl CoA synthetase

The Peer Teaching Society is not liable for false
or misleading information
30
Fatty acid oxidation/ Beta oxidation
The carnitine shuttle !!!

The Peer Teaching Society is not liable for false
or misleading information
31
The Carnitine Shuttle
Carnitine
CoA
Acyl CoA
Acyl Carnitine
Carnitine Acyl Transferase I

The Peer Teaching Society is not liable for false
or misleading information
32
Inner mitochondrial membrane
CoA
Carnitine
Acyl Carnitine
Acyl CoA
Carnitine Acyl Transferase II

The Peer Teaching Society is not liable for false
or misleading information
33
Fatty acid oxidation/ Beta oxidation

Acetyl CoA
Acyl CoA
Acyl CoA 2C

• Sequential removal of 2- carbon units
• Each round of ß-oxidation produces
• 1 mole of NADH
• 1 mole of FADH2
• 1 mole of acetyl-CoA

The Peer Teaching Society is not liable for false
or misleading information
34
Ketogenesis

• The process by which ketone bodies are produced
  as a result of fatty acid breakdown.
• Ketones are used for energy at low fat states.

The Peer Teaching Society is not liable for false
or misleading information
35
Ketogenesis
2 Acetyl-CoA
CoA-SH
thiolase
Acetoacetyl-CoA
Acetyl-CoA H20
HMG-CoA synthase
CoA-SH
HMG-CoA
HMG-CoA lyase
Acetyl-CoA
Acetoacetate

Acetone
ß- hydroxybutyrate
The Peer Teaching Society is not liable for false
or misleading information
36
I know, no pathology
Diabetic ketoacidosis

• Reduced supply of glucose due to a significant
  decline in circulating insulin and an associated
  increased in circulating glucagon.
• The increased production of Acetyl-CoA leads to
  ketone body production
• This lowers the pH of the blood

The Peer Teaching Society is not liable for false
or misleading information
37
Acid/Base/Buffer

• Acid proton (H) donor
• HA ? H A-
• Base proton (H) acceptor
• B H ? BH
• Buffer weak acids or bases that act to maintain
  H concentration

The Peer Teaching Society is not liable for false
or misleading information
38
Acid/base/buffer

• Acidosis can either be respiratory or metabolic
• Alkalosis can either be respiratory or metabolic
• pH range is 7.35-7.45. But ideal pH is 7.4
• Compensation metabolic is slow, respiratory is
  fast.

The Peer Teaching Society is not liable for false
or misleading information
39
Henderson-Hasselbalch equation

• Hendersons formula-
• H x HCO3 - K x pCO2
• Hasselbalch converted it to pH
• pH pK log (HCO3 - / CO2)

The Peer Teaching Society is not liable for false
or misleading information
40
Acidosis
Carbonic anhydrase

• Respiratory
• Insufficient ventilation retains CO2 so there is
  more carbonic acid in the blood leading to
  acidosis
• Causes include COPD (chronic bronchitis
  emphysema), asthma

• Metabolic
• Low bicarbonate levels leading to acidosis
• Causes include bicarbonate losses from the GI
  tract e.g. diarrhoea, DKA, lactic acidosis
  (anaerobic respiration), renal failure

The Peer Teaching Society is not liable for false
or misleading information
41
Alkalosis

• Respiratory
• Blowing off too much CO2 leading to alkalosis
• Causes hyperventilation, pink puffers COPD (i.e.
  type 1 respiratory failure), anxiety, fever

• Metabolic
• Loss of H or too much bicarbonate leading to
  alkalosis
• gastric secretions contain large quantities of
  hydrogen ions.
• Causes include excess vomiting (because youre
  losing H), pyloric stenosis, anorexia nervosa,
  ingestion of bicarbonate

The Peer Teaching Society is not liable for false
or misleading information
42
Anion Gap

• The anion gap is calculated by subtracting the
  serum concentrations
• of ANIONS (Cl- and HCO3-) from the concentrations
  of CATIONS (Na and K)
• BUT
•  potassium concentrations, being very low,
  usually have little effect on the calculated gap.
  This leaves the following equation
• Anion gap Na - (Cl- HCO3-) 16 meq/lit

The magnitude of this difference (i.e., "gap") in
the serum is often calculated when attempting to
identify the cause of metabolic acidosis. If
the gap is greater than normal, then high anion
gap metabolic acidosis is diagnosed (due to
increased cation H)
The Peer Teaching Society is not liable for false
or misleading information
43
Types of Buffer systems

• Proteins (51)
• Weak acid/base groups
• Bicarbonate (43)
• CO2 removed via lungs, Bicarbonate regenerated by
  kidneys
• Haemoglobin (6)
• Deoxy Hb binds H ? HHb Bicarbonate
• Amine group on Deoxy Hb bind CO2
  ?carbaminohaemoglobin

? Most important
Haemoglobin binds both CO2 and H and so is a
powerful buffer
The Peer Teaching Society is not liable for false
or misleading information
44
Oxygen Toxicity

• Toxic reactive oxygen derivatives with
• Free radicals
• Unpaired electrons in outer shell
• High reactivity
• OR
• DEF Chemically reactive molecules with unpaired
  electrons in outer shell free radicals
  (unpaired electron) derived from oxygen

The Peer Teaching Society is not liable for false
or misleading information
45
Formation of ROS
Generates radicals with transition metals (Fenton
or Haber Weiss rx)
Produced by ETC
The Peer Teaching Society is not liable for false
or misleading information
46
ROS

• OH (hydroxyl radical)
• Most potent radical
• Lipid soluble
• Chain reaction forms lipid peroxides organic
  radicals
• H202 (hydrogen peroxide)
• Not actually a radical
• Oxidising agent in presence of Fe2 or other
  transition metals
• Generates hydroxyl radical
• Lipid soluble

The Peer Teaching Society is not liable for false
or misleading information
47
Formation of hydroxyl radical
Haber-Weiss reaction
Fenton reaction
-
O2
H2O2


H2O2
Fe2
H
O2
Fe3


H2O
OH


OH
OH-
The Peer Teaching Society is not liable for false
or misleading information
48
Production of ROS

• Endogenous
• natural by-product of O2 metabolism
• Produced mainly inside cell organelles ie.
  (mitochondria)
• Exogenous
• UV radiation, smoking, inflammation

The Peer Teaching Society is not liable for false
or misleading information
49
ve ROS

• Respiratory bursts
• ROS released during phagocytosis of bacteria
• Damages bacterial cell membrane
• Fentons reaction
• O2 ? O2-?H2O2Fe2?Fe3 OH- OH

The Peer Teaching Society is not liable for false
or misleading information
50
-ve ROS

• Cellular damage
• Damage to membranes of nucleus, mitochondria,
  endoplasmic reticulum cell
• Increased permeability leads to influx of
  calcium, water sodium

The Peer Teaching Society is not liable for false
or misleading information
51
Anti-oxidants

• Enzymes
• Catalase H2O2 ? 2 H20 02
• Superoxide dismutase O2- ? H2O2
• Glutathione peroxidase
• Antioxidant vitamins/Free radical scavengers
  (vitC, vitE, carotenoids)
• Cellular Compartmentation
• Repair

The Peer Teaching Society is not liable for false
or misleading information
52
Histology of Epithelia

• Roles of epithelia
• Protection(skin)
• Absorption(gut)
• Secretion(pancreas)

Simple Epithelium
Stratified Epithelium -Almost always squamous
Pseudo-stratified Epithelium

The Peer Teaching Society is not liable for false
or misleading information
53
Simple squamous epithelia
Found in -Alveoli -Serosa
The Peer Teaching Society is not liable for false
or misleading information
54
Simple cuboidal epithelia

• Found in
• -Kidney tubules
• -Ducts of glands
• Sweat
• Salivary
• Pancreatic

The Peer Teaching Society is not liable for false
or misleading information
55
Simple columnar epithelia

• Found in
• -Small intestine
• -Gall bladder
• -Bronchus

The Peer Teaching Society is not liable for false
or misleading information
56
Stratified epithelium

• Protection
• Continually being worn down
• Cells replaced from below
• Found in areas where there is continuous abrasion
• Squamous
• ?Keratinised skin
• ?Non keratinised mouth, oesophagus, vagina
• Cuboidal
• found in some large ducts

The Peer Teaching Society is not liable for false
or misleading information
57

• Stratified squamous non-keratinising
• Found in
• Mouth
• Oropharynx
• Oesophagus
• Vagina

The Peer Teaching Society is not liable for false
or misleading information
58
Stratified squamous keratinising

• Found in
• -Skin (hairy or non-hairy skin)

The Peer Teaching Society is not liable for false
or misleading information
59
Pseudostratified columnar epithelia

• Found in
• Trachea and large airways (respiratory
  epithelium)
• Urinary tract

The Peer Teaching Society is not liable for false
or misleading information
60
Cell Junctions

• 1) Adherent (tight) junctions

The Peer Teaching Society is not liable for false
or misleading information
61
Cell Junctions

• 2) Desmosome

The Peer Teaching Society is not liable for false
or misleading information
62
Cell Junctions

• 3) Gap junction

The Peer Teaching Society is not liable for false
or misleading information
63
Staining
The Peer Teaching Society is not liable for false
or misleading information
64
Alcian Blue
GAG-rich structuresMucous goblet cellsMast
cell granulesCartilage matrix
The Peer Teaching Society is not liable for false
or misleading information
65
Staining
The Peer Teaching Society is not liable for false
or misleading information
66
Eosin
Colloidal proteins (e.g. plasma)Keratin
The Peer Teaching Society is not liable for false
or misleading information
67
Staining
The Peer Teaching Society is not liable for false
or misleading information
68
Haematoxylin
NucleiRNA
The Peer Teaching Society is not liable for false
or misleading information
69
Staining
The Peer Teaching Society is not liable for false
or misleading information
70
PAS
Hexose sugars
The Peer Teaching Society is not liable for false
or misleading information
71
Questions?
asinha1_at_sheffield.ac.uk rcsabaratnam1_at_sheffield.a
c.uk
The Peer Teaching Society is not liable for false
or misleading information