General Pathology Illustrations Dr. Cooperstein

1
General Pathology IllustrationsDr. Cooperstein

• Summer 2009

2
William Boyd, MD
Another William Boyd
3
Causes of DiseaseThe case of cancer
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PathophysiologyA causal explanation

• Structural changes
• Disturbed function
• Structure ? function
• Questions for the doctor
• Diagnosis what disease
• Prognosis what will happen
• Treatment
• Cause of the disease

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The cell and its organelles
6
The 3D Cell
7
Plasmalemma

• Structural envelope
• Selects macromolecules leaving and entering
• Maintains ionic concentration difference inside
  and outside

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Acetylcholine receptor
9
ACH receptor w/axon
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The mitochondrion Power plant of the cell
11
Birth of complex cells
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Mitochondrial Eve . . .
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Adam African also . . .
DNA tests trace Adam to Africa By Steve Connor,
Science Correspondent. Sunday Times, 9th November
1997 ALL men can trace their ancestry back to
one man who lived 150,000 years ago and whose
closest living relatives are a small tribe in
South Africa, according to scientists who have
spent a decade searching for the original
Adam. Research into the human Y chromosome
which sons only inherit from their fathers has
pinpointed the time and place where just one man
gave rise to the male genetic ingredients of all
men alive today. The geneticists have also
located the oldest direct descendants of this
Adam, who they say lived alongside an African Eve
who was identified in similar studies 10 years
ago. The Khoisan people of South Africa, some
with a hunter-gatherer tradition stretching back
thousands of years, share most of the genetic
traits that first arose when Adam hunted game and
collected berries in his African Garden of Eden.
Two independent investigations of minute
mutations on the Y chromosome pinpointed the
Khoisan people, who are also known as Bushmen or
Hottentots, as the only ethnic group to possess
so many ancient remnants of the original Adam.
Dr Michael Hammer, a geneticist at the
University of Arizona, analysed the Y chromosome
of more than 1,500 men selected from ethnic
groups around the world and found a clear line of
descendent from the African Adam to the
present-day Khoisan people. "One way of looking
at this is that the Y chromosome traces back to
people who lived in Africa. We have evidence that
the Y chromosomes in all men today trace back to
one African male at some time in the past," he
said. "It is possible that this male was not
anatomically modern. He may have been more like
Homo erectus, one of our hominid ancestors, but
his Y chromosome survived the change in the way
we look."
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Ribosome
15
Ribosome structure
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The LysosomeCellular Recycling
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Nuclear pore and ER
The nuclear envelope has two membranes, each with
the typical unit membrane structure. They enclose
a flattened sac and are connected at the nuclear
pore sites. The outermost membrane is continuous
with the rough endoplasmic reticulum (ER) and has
ribosomes attached.
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Nuclear changes

• Pyknosis Shrinking and darkening of the nucleus
• Karyolysis Fading (dissolving) of the nucleus
• Karyorrhexis Fragmentation of the nucleus

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Nuclear changes, another look
20
Pyknosis irreversible

• It is difficult to define a "point of no return"
  but once changes to the nucleus take place (i.e.
  pyknosis, karyorrhexis and karyolysis) and cell
  membranes are disrupted the cell is on the path
  to irreversible injury and death.

21
Royal Pyknosis?
22
Pyk-nosis . . .
23
Reversible and irreversible cellular changes
24
Hydropic swelling
25
Goiter, endemic
26
Castration cost effective
27
Strange case of Kenny and Dolly
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Graves Disease
The runaway bride . . .
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Hyperplasia in muscles?
Morphological observations supporting muscle
fiber hyperplasia following weight-lifting
exercise in cats C. J. Giddings, W. J. Gonyea,
Ph.D. Abstract Although exercise-induced
muscle fiber hyperplasia has been demonstrated
through direct fiber counts following nitric-acid
digestion of muscle, morphological studies to
determine the mechanism of hyperplasia have not
been performed previously. In this study, light
and electron microscopy were used to evaluate
evidence of muscle fiber splitting or de novo
formation of new muscle fibers. Since both fiber
hypertrophy and hyperplasia may result in
alterations in the muscle nuclear populations,
myonuclear number and satellite cell frequency
were assessed quantitatively to determine their
role in regulating muscle fiber size. Ten adult
cats performed weight-lifting exercise, . .
These findings confirm previous studies
demonstrating muscle fiber hyperplasia following
weight-lifting exercise, and suggest that de novo
fiber formation is the major mechanism
contributing to muscle fiber hyperplasia in this
model.
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Skeletal muscle hyperplasia

• Journal of Applied Physiology, Vol. 81, No. 4,
  pp. 1584-1588, October 1996
• Mechanical overload and skeletal muscle fiber
  hyperplasia a meta-analysis George Kelley
• With use of the meta-analytic approach, the
  purpose of this study was to examine the effects
  of mechanical overload on skeletal muscle fiber
  number in animals. A total of 17 studies yielding
  37 data points and 360 subjects met the initial
  inclusion criteria 1) "basic" research studies
  published in journals, 2) animals (no humans) as
  subjects, 3) control group included, 4) some type
  of mechanical overload (stretch, exercise, or
  compensatory hypertrophy) used to induce changes
  in muscle fiber number, and 5) sufficient data to
  accurately calculate percent changes in muscle
  fiber number. Across all designs and categories,
  statistically significant increases were found
  for muscle fiber number 15.00 19.60 (SD), 95
  confidence interval 8.65-21.53, muscle fiber
  area (31.60 44.30, 95 confidence interval
  16.83-46.37), and muscle mass (90.50 86.50,
  95 confidence interval 61.59-119.34). When
  partitioned according to the fiber-counting
  technique, larger increases in muscle fiber
  number were found by using the histological vs.
  nitric acid digestion method (histological
  20.70, nitric acid digestion 11.10 P
  0.14). Increases in fiber number partitioned
  according to species were greatest among those
  groups that used an avian vs. mammalian model
  (avian 20.95, mammalian 7.97 P 0.07).
  Stretch overload yielded larger increases in
  muscle fiber number than did exercise and
  compensatory hypertrophy (stretch 20.95,
  exercise 11.59, compensatory hypertrophy
  5.44 P 0.06). No significant differences
  between changes in fiber number were found when
  data were partitioned according to type of
  control (intra-animal 15.20, between animal
  13.90 P 0.82) or fiber arrangement of muscle
  (parallel 15.80, pennate 11.60 P 0.61).
  The results of this study suggest that in several
  animal species certain forms of mechanical
  overload increase muscle fiber number.

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Cardiac muscle hyperplasia

• Are adult cardiocytes still able to proliferate?
  (Swynghedauw B.)
• In all mammals including humans, adult
  cardiocytes become post mitotic cells, while
  cardiac non muscle cells still have the capacity
  to proliferate, and cardiac hypertrophy in adults
  is known to be due to cardiocyte hypertrophy and
  non muscle cell hyperplasia. Such a dogma was
  supported by several, rather ancient,
  observations, and has been recently challenged by
  two different groups. Several new paradigms in
  cell biology have modified these views the
  entire determinants of the cell cycle are now
  entirely known apoptosis, and cardiac apoptosis,
  is central in the process of cell division, and
  has a rather complicated significance telomeres
  are specialized DNA-protein structures that
  prevent end-to-end chromosome fusion, and are
  rather characteristic of germ and stem cells,
  these structures are maintained by telomerase.
  Using several markers, including telomerase
  activity, endogenous self-renewing, clonogenic
  and multipotent stem cells were identified in the
  adult myocardium in human, mice and rat. These
  cells are activated during cardiac overload or
  ischemia to produce new cardiocytes. New
  endothelial cells also appeared, and are likely
  to have a circulatory origin. The physiological
  importance of these new cells is debatable at the
  moment. Nevertheless, these findings provide an
  important new basis for cell cardiomyoplasty. It
  is also possible to envisage stimulation of the
  production and activity of these new cells to
  compensate for the lack of substance after
  myocardial infarction.

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Myeloid, lymphoid tissue
33
Reed-Sternberg cells
34
Graves Disease
The runaway bride . . .
35
Hyperplasia in muscles?
Morphological observations supporting muscle
fiber hyperplasia following weight-lifting
exercise in cats C. J. Giddings, W. J. Gonyea,
Ph.D. Abstract Although exercise-induced
muscle fiber hyperplasia has been demonstrated
through direct fiber counts following nitric-acid
digestion of muscle, morphological studies to
determine the mechanism of hyperplasia have not
been performed previously. In this study, light
and electron microscopy were used to evaluate
evidence of muscle fiber splitting or de novo
formation of new muscle fibers. Since both fiber
hypertrophy and hyperplasia may result in
alterations in the muscle nuclear populations,
myonuclear number and satellite cell frequency
were assessed quantitatively to determine their
role in regulating muscle fiber size. Ten adult
cats performed weight-lifting exercise, . .
These findings confirm previous studies
demonstrating muscle fiber hyperplasia following
weight-lifting exercise, and suggest that de novo
fiber formation is the major mechanism
contributing to muscle fiber hyperplasia in this
model.
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Myositis Ossificans

• aberrant reparative process causing benign
  heterotopic (extraskeletal) ossification in soft
  tissue

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Squamous Metaplasia of Bladder

• Etiology
• The etiology of squamous metaplasia is dependent
  upon the underlying pathologic process, i.e,
  bladder calculi, extrophy of the bladder,
  schistosomiasis.
• Probably normal in women.
• Pathogenesis
• The normal transitional epithelium will undergo
  squamous metaplasia as an adaptive change to
  chronic irritation, such as from bladder calculi.
• Epidemiology
• The epidemiology is dependent on the underlying
  disease process.
• Squamous metaplasia is found in a large
  percentage of women with no abnormalities.
• General Gross Description
• There is no striking gross changes to the
  epithelial lining of the bladder.
• There may be a perception that the epithelial
  lining is paler and thicker than normal.
• General Microscopic Description
• The normal transitional epithelium of the bladder
  is replaced by stratified squamous epithelium.
• Clinical Correlation
• Squamous metaplasia may occur in situations of
  chronic irritation such as bladder calculi,
  extrophy of the bladder and schistosomiasis.
• References
• Cotran RS, Kumar V, Robbins SL Robbins
  Pathologic Basis of Disease. 5th ed.
  Philadelphia, W.B. Saunders, 1994, pp. 48

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HypothyroidismClinical Features
Rubin and Farber, p 1111
39
Dysplasia, cervical
40
Dysplasia, bronchial
Sections from human bronchial biopsies . . .
Representative stains of normal (A), mild
dysplasia (B), moderate dysplasia (C) and severe
dysplasia (D).
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Breast cancer and diet
42
Etiology of Tissue injury
43
Creatine phosphokinase isoenzymes

• CPK isoenzymes are performed when the total CPK
  level is elevated. Isoenzyme testing can help
  differentiate the source of the damaged tissue.
• CPK is an enzyme found predominantly in the
  heart, brain, and skeletal muscle. CPK is
  composed of 3 isoenzymes that differ slightly in
  structure
• CPK-1 (also called CPK-BB) is concentrated in the
  brain and lungs
• CPK-2 (also called CPK-MB) is found mostly in the
  heart
• CPK-3 (also called CPK-MM) is found mostly in
  skeletal muscle
• Because the CPK-1 isoenzyme is predominately
  found in the brain and lungs, injury to either of
  these organs (for example, stroke or lung injury
  due to a pulmonary embolism) are associated with
  elevated levels of this isoenzyme.
• CPK-2 levels rise 3 - 6 hours after a heart
  attack . If there is no further damage to the
  heart muscle, the level peaks at 12 - 24 hours
  and returns to normal 12 - 48 hours after tissue
  death. CPK-2 levels do not usually rise with
  chest pain caused by angina , pulmonary embolism
  (blood clot in the lung), or congestive heart
  failure .
• The CPK-3 isoenzyme is normally responsible for
  almost all CPK enzyme activity in healthy people.
  When this particular isoenzyme is elevated, it
  usually indicates injury or stress to skeletal
  muscle.

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Ischemia
45
Chemical Injury

• Carbon tetrachloride
• Phospholipase C
• Mercury

46
Dietary antioxidants
47
Free radicals
Free radical damage
Anti-oxidants
48
Free radical chemistry

• Chain
• Initiation
• Propagation
• Termination
• Anti-oxidant scavengers
• Vitamins
• C, E, beta-carotene
• Minerals
• Selenium, etc.

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Eating SOD . . .
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Ondrox ingredients

• Ondrox Antioxidant Ingredients
• Two tablets contain
• Vitamin A (as beta carotene and retinol acetate)
  12000 I.U.
• Vitamin C (ascorbic acid, niacinamide ascorbate)
  250 mg
• Vitamin D (as cholecalciferol) 600 I.U.
• Vitamin E (dl-alpha tocopherol acetate) 100
  I.U.
• Vitamin K (phytonadione) 25 mcg
• Vitamin B1 (thiamine mononitrate) 1.5 mg
• Riboflavin 1.7 mg
• Niacin (niacinamide ascorbate) 20 mg
• Vitamin B6 (pyridoxine hydrochloride) 2 mg
• Folate (as folic acid) 400 mcg
• Vitamin B12 (as cobalamin) 6 mcg
• Biotin 30 mcg
• Pantothenic Acid (calcium pantothenate) 10 mg
• Calcium (citrate, 100 mg
• Phosphorus (dibasic calcium phosphate) 20 mg
• Iodine (potassium iodide) 150 mcg
• Magnesium (oxide) 40 mg

51
DNA repair enzymesdelivered via liposomes
52
Beta-carotene, potential problem

• When beta-carotene is consumed in amounts found
  naturally in foods, or when consumed in oral
  supplement doses of 15mg/day or less in people
  with good general health, when used orally and
  appropriately. Beta-carotene is likely safe in
  children, when used orally in amounts commonly
  found in foods. Beta-carotene is likely safe in
  pregnant and lactating women, when used orally
  and appropriately in amounts commonly found in
  foods.
• Carcinogenic Beta-carotene in doses of 20mg
  daily for 5-8 years has been associated with an
  increased risk of lung and prostate cancer and
  increased total mortality in people who smoke
  cigarettes, and in people with a history of
  high-level asbestos exposure. Smokers and people
  with a history of asbestos exposure should not
  use beta-carotene supplements. These adverse
  effects do not seem to occur in people who eat
  foods high in beta-carotene content.
• Cardiovascular In people who smoke,
  beta-carotene 20 to 30mg daily may increase
  cardiovascular mortality by 12 to 26. In men
  who smoke and have had a prior myocardial
  infarction (MI), the risk of fatal coronary heart
  disease increases by as much as 43 with
  beta-carotene 20mg daily. There is some evidence
  that beta-carotene in combination with selenium,
  vitamin C and vitamin E might lower high-density
  lipoprotein 2 (HDL2) cholesterol levels. HDL
  levels are protective so this is considered to be
  a negative effect.

53
Vitamins and cancer
54
Tomatoes fail as prostate cancer preventive
A new study suggests that eating lycopene-rich
tomatoes offers no protection against prostate
cancer, contrary to the findings of some past
studies. In fact, the researchers found an
association between beta carotene, an antioxidant
related to lycopene, and an increased risk of
aggressive prostate cancer. . . .Unexpectedly,
the investigators noted an association between an
increased risk of aggressive prostate cancer --
defined as disease that has spread beyond the
prostate -- and higher intake of beta carotene,
another antioxidant found in many vegetables and
commonly used as a dietary supplement. Although
this observation "may be due to chance," Peters
added, "beta carotene is already known to
increase the risk of lung cancer and
cardiovascular disease in smokers." "While it
would be counter-productive to advise people
against eating carrots and leafy vegetables, I
would say to be cautious about taking beta
carotene supplements, particularly at high doses,
and consult a physician," Peters said. SOURCE
Cancer Epidemiology, Biomarkers and Prevention,
May 2007.
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Nutrients robbed . . .
56
Microwave ovens andfree radicals
It's doubtful that microwave cooking forms free
radicals in food. The microwaves in a microwave
oven cook by exerting torques on the water
molecules and gradually increasing the water
molecules' thermal energies through friction-like
effects. There is never enough energy present in
a single molecule at one time to shatter that
molecule and form a free radical. While
ultraviolet light, such as that found in
sunlight, carries enough energy per photon
(particle of light) to split a molecule and form
a free radical, microwave radiation carries very
little energy per photon. That's why microwave
photons can't do chemical damage the way
ultraviolet photons can. However, even if
microwave radiation could form free radicals in
food, that wouldn't necessarily cause you trouble
when you eat that food. So much happens to the
food before it enters your blood stream that a
free radical probably won't survive. The more
harmful free radicals are ones that are actually
created inside your body, where they can
immediately attack important molecules in your
cells. http//howthingswork.virginia.edu/page1.php
?QNum318
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Ionizing radiation
Cancer
58
X-ray heretic Gofman
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Gofmans on-line book
By reasonable standards of proof, the safe-dose
hypothesis is not merely implausible -- it is
disproven. Disproof of any safe dose
or dose-rate invalidates suggestions that,
whenever an analyst calculates a number of
radiation-induced cancers to be caused by very
low-dose exposure, the cancers are just
"hypothetical," "speculative," "theoretical,"
"non-existent," or "imaginary." It is
true, of course, that radiation-induced cancers
in a population from very low doses will rarely
if ever be detectable epidemiologically, because
of the signal-to-noise ratio (see Chapter 21).
But it does not follow (from the lack of direct
observation) that the cancers are therefore
unreal, hypothetical, speculative, theoretical,
non-existent, or imaginary. No rational person
will deny that one of the most commonplace (and
important) functions of science is to let people
know what is really happening when direct
observation is impossible. We conclude
with a warning Disproof of any safe dose or
dose-rate means that fatal cancers from minimal
doses and dose-rates of ionizing radiation are
not imaginary. They are really occurring in
exposed populations. Proposals, to declare that
they need not be considered, have health
implications extending far beyond the radiation
issue, as pointed out in Chapter 24, Part 10 and
Chapter 25, Part 5.
Radiation-Induced Cancer From Low-Dose Exposure
John W. Gofman, M.D., Ph.D. 1990.
http//www.ratical.org/radiation/CNR/RIC/contentsF
.html
60
Health effects of chiropractic x-ray
61
X-Ray Hormesis
Oakley PA, Harrison DD, Harrison DE, Haas JW. A
Rebuttal to Chiropractic Radiologists' View of
the 50-year-old, Linear-No-Threshold Radiation
Risk Model. JCCA J Can Chiropr Assoc
200650(3)172-81.
62
Current epidemiological evidence regarding the
health effects of low-dose ionizing radiation.
Implications for radiation protection, public
health and forensic medicine (2004)
The health effects of low-dose ionizing radiation
have been widely studied, but remain uncertain.
Up-to-date knowledge about epidemiologic evidence
for potential human health effects of low dose
ionizing radiation is important for revising
national radiation protection legislation. This
review, conducted by a multidisciplinary research
team of the Italian Institute of Social Medicine,
evaluates epidemiologic studies published since
July 2003. After careful selection, a total of
302 studies were reviewed. Greater emphasis was
given to papers that analyzed data using
standardized incidence and mortality ratios and
to studies regarding occupational exposures in
all workers, healthcare workers and aircrew
members. Nevertheless, studies regarding A-bomb
survivors of Hiroshima/Nagasaki, Chernobyl
cleanup workers, patients exposed for medical
reasons, and workers in nuclear plants were also
included. Given the limitations of
epidemiological studies and excluding the cosmic
rays context, which requires further research,
the authors conclude that harmful effects from
exposures to ionizing radiation at doses lower
than 100 mSv cannot be ruled out. Nevertheless,
if any harmful health effects do exist, they are
certainly very small. The implications for
radiation protection, public health and forensic
medicine are discussed.
63
CT scans and cancer
64
Microbes

• Bacteria
• Exotoxins
• Enterotoxins
• Endotoxins
• Viruses

65
Physical agents

• Extremes of temperature
• Changes in pressure
• Radiation
• Electrical currents

66
Intracellular accumulations
67
Fatty change, pancreas and heart
The normal pancreas in younger and thinner
patients is less hyperechoic than the fat around
the superior mesenteric artery and more
hyperechoic than the left lobe of the liver. With
advancing age and/or increasing body weight, the
acinar tissue progressively atrophies and is
replaced by fatty tissue. This causes the
pancreas to increase uniformly in echogenicity.
The appearance of a fatty pancreas can be seen in
a number of conditions (1) elderly, (2) obese,
(3) diabetes mellitus, (4) Cushing's disease, (5)
lipomatosis, and (6) after steroid
administration. Fatty Heart. This is a
condition in which there is a deposit of fat
between the sac which contains the heart and the
heart muscle. The trouble is directly associated
with obesity, and is dietetic in origin, being
attributable to over-indulgence in food and
drink. Shortness of breath on exertion and a
feeling of distress or oppression in the region
of the heart are its most marked symptoms.
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Necrosis

• Liquefaction Necrosis Watery breakup of cells
  usually caused by bacterial enzymes or some body
  reaction to microbial infection.
• Coagulation Necrosis "Coagulation" of cells in
  which tissue details remain usually caused by
  sudden loss of blood supply.
• Caseous Necrosis Accumulation of a "cheesy"
  material in an area of tissue injury usually
  caused by infection with the organism of
  tuberculosis (Mycobacterium tuberculosis).
• Gummatous Necrosis Accumulation of a "gummy"
  material in an area of tissue injury usually
  caused by infection with the organism of syphilis
  (Treponema palladium).
• Fat Necrosis Death of adipose cells (fat
  deposits) usually caused by release of
  fat-splitting enzymes into the tissues.
• Gangrenous Necrosis Death of cells in an
  extremity (e.g., toe) caused by ischemia and
  (sometimes) superimposed bacterial infection.

69
Fatty necrosis, pancreas
Pancreatic Fat NecrosisThis is a gross
photograph of a remnant of canine pancreas ()
which has experienced repeated bouts of acute
pancreatitis. After each bout, pancreatic lipases
are released which, in turn, digest mesenteric
adipose tissue. This produces necrosis of fat
cells, release of free fatty acids and a further
inflammatory response (Arrow). The process will
continue until the pancreas is destroyed or until
the damage to the abdomen is so great as to cause
death. http//www.vet.ohio-state.edu/docs/vetbio5
50.01/necrosis/fatnec.html
70
Acute pancreatitis andenzymatic destruction
Discrete white areas of fat necrosis are present
in the pancreatic parenchyma. The destruction of
the pancreas, in this case of acute pancreatitis,
is not extensive
Discrete, white areas of fat necrosis are present
in the omentum of this patient with severe,
pancreatitis (acute hemorrhagic pancreatitis).
http//zappa.ultrakohl.com/medstud/PicGal/actpan2.
htm
71
Pancreatitis major causes

• The major causes are long-standing alcohol
  consumption or biliary stone disease.
• The most common cause of acute pancreatitis in
  developed countries is alcohol abuse.
• On the cellular level, ethanol leads to
  intracellular accumulation of digestive enzymes
  and their premature activation and release.
• On the ductal level, ethanol increases the
  permeability of ductules, which allow enzymes to
  reach the parenchyma, resulting in pancreatic
  damage.
• Ethanol increases the protein content of the
  pancreatic juice and decreases bicarbonate levels
  and trypsin inhibitor concentrations. This leads
  to the formation of protein plugs that block the
  pancreatic outflow and obstruction.
• Another major cause of acute pancreatitis is
  biliary stone disease (cholelithiasis and
  choledocholithiasis).
• A biliary stone may lodge in the pancreatic duct
  or ampulla of Vater and obstruct the pancreatic
  duct, leading to extravasation of enzymes into
  the parenchyma.

72
Wet and dry gangrene
73
Dry gangrene(as in diabetes m.)
74
Tissue storage disorders
75
Fatty liver
76
Ethanol and cirrhosis of the liver
77
HDL vs LDL
HDL (High density lipoprotein) Carries
cholesterol in blood from cells to liver Liver
cells have HDL receptors Endocytose HDL
Excrete to bile HDL removes
cholesterol from body LDL carries
cholesterol to cells Cholesterol forms
plaques in blood vessels Clogs arteries
Causes heart attacks
78
Hepatitis B

• Prognosis Hepatitis B
• Outcome in adults and children over age 5 years
• Recovery 90
• Chronic Active Hepatitis 10
• Fulminant Hepatitis
• Outcome in children under age 5 years
• Chronic infection 30-90
• Worse prognosis if Hepatitis D also present
• Cirrhosis higher risk
• Hepatocellular Carcinoma higher risk
• Prognosis Hepatitis A
• Over 85 of people with hepatitis A recover
  within 3 months, and over 99 of people recover
  by 6 months.
• The fatality rate is estimated at 0.1, usually
  among the elderly and patients with chronic liver
  disease.
• Hepatitis A virus does not become a chronic
  infection.
• Prognosis Hepatitis C
• Hepatitis C is one of the most common causes of
  chronic liver disease in the U.S. today. At least
  80 of patients with acute hepatitis C ultimately
  develop chronic liver infection, and 20 to 30
  develop cirrhosis. Between 1 and 5 of patients
  may develop liver cancer. Hepatitis C is now the
  number 1 cause for liver transplantation in the
  U.S.

79
Eggs have gotten a bad rap!
80
Animal and plant sterols
Cholesterol is the sterol of mammalian cells.
ß-Sitosterol is the most common sterol in plants
it differs from cholesterol by having an ethyl
group attached at C-24. Hydrogenation of the 5,6
double bond of ß-sitosterol converts it into
sitostanol.5 Campesterol and campestanol carry a
methyl instead of ethyl group at C-24.
There is growing evidence that plant sterols/
stanols help in lowering total and low density
lipoprotein (LDL) cholesterol levels and that
this effect is additive to that achieved by
dietary fatty acid manipulation.
81
Soy and LDL cholesterol Then and now
Science giveth and science taketh away . . .
THEN The Soy Health Claim In October 1999, FDA
approved a health claim that can be used on
labels of soy-based foods to tout their
heart-healthy benefits. The agency reviewed
research from 27 studies that showed soy
protein's value in lowering levels of total
cholesterol and low-density lipoprotein (LDL, or
"bad" cholesterol). Food marketers can now use
the following claim, or a reasonable variation,
on their products "Diets low in saturated fat
and cholesterol that include 25 grams of soy
protein a day may reduce the risk of heart
disease. One serving of (name of food) provides
__ grams of soy protein." To qualify for the
claim foods must contain per serving 6.25 grams
of soy protein, low fat (less than 3 grams), low
saturated fat (less than 1 gram), low cholesterol
(less than 20 milligrams), sodium value of less
than 480 milligrams for individual foods, less
than 720 milligrams if considered a main dish,
and less than 960 milligrams if considered a
meal.
NOW Lowering cholesterol properties of soy
disproved by study Posted on Tue, 24 Jan 2006
000200 GMT Author Ryan Jones According to
the findings of a committee of the American Heart
Association, benefits of soy-based food in
lowering cholesterol have been overstated.
Twenty two studies carried out on soy products
analyzed by the committee revealed that they had
very few benefits for the heart. Researchers go
on to add that soy when taken in large amounts
only shows slight decline in low-density
lipoproteins (LDL), also known as bad
cholesterol, and none whatsoever on HDL, known as
good cholesterol.
82
Carpal tunnel syndrome and hypothyroidism
Carpal Tunnel Syndrome and Hypothyroidism
Hypothyroidism May Be the Cause of Many Carpal
Tunnel Cases August 1998 -- Until recently,
despite much research on the subject, many
doctors and endocrinologists have not been
generally aware of the connection between carpal
tunnel syndrome (CTS) and hypothyroidism. CTS is
a repetitive strain injury (RSI) that manifests
itself as pain, achiness or numbness in the
wrist, fingers or forearm. It is due to swelling
of membranes that compress a nerve in the
forearm, and is more common in people with
hypothyroidism.
83
Bilirubin metabolism
84
Addisons disease The hand
In their experience with 108 cases of Addisons
disease, Rowntree and Snell noted that asthenia,
weight loss, gastrointestinal symptoms (anorexia,
nausea, vomiting, and abdominal pain), and
hypotension were almost always part of the
syndrome. Hyperpigmentation was present in most
cases and was described in such terms as a
suntan which does not wear off ... tinged
somewhat with blue or gray . . . dirty in
appearance. The exposed portions of the body
(hands, face, neck, and arms), points of pressure
and friction, nipples, freckles, recently formed
scars, genitalia, and creases of the palms often
showed exaggerated pigmentation. Brown, blue, or
gray spots on the lips and buccal mucous
membranes were common. (Cecils)
85
Occupational Lung Disease
Pneumoconioses are caused by dust that gets into
the lungs. Hypersensitivity diseases such as
asthma are caused by the lungs' overreaction to
airborne pollutants. Asbestosis This disorder is
caused by breathing dust from asbestos, the
fireproofing and insulating product often used in
the past to wrap water pipes and line furnaces
and air conditioning ducts. During its heyday,
asbestos was also compressed into floor tiles and
was even woven into movie theater curtains, hot
pads, and ironing board covers. Asbestos dust can
cause inflammation and widespread scarring in the
lungs. Berylliosis This is a lung inflammation
caused by inhaling dust or fumes that contain
beryllium, a substance widely used in the
aerospace industry and employed in the
manufacture of fluorescent bulbs. Black Lung
Also known as coal workers' pneumoconiosis (CWP),
this disease is found exclusively in coal miners.
Caused by inhaling coal dust, it is marked by
scarring in the lungs. Byssinosis The hallmark
of this condition is a temporary narrowing of the
airways after inhaling particles of cotton, flax,
or hemp. The disorder is found almost exclusively
in those who work with unprocessed cotton.
Occupational asthma The intermittent breathing
problems that mark this disorder can be brought
on by a wide variety of substances, including
paint, hair bleach and dye, foam and packaging
materials that emit chemical dusts or vapors,
animal hair and dander, organic dust from milled
or ground food (such as flour and coffee), dust
from textiles, and metals such as chromium and
nickel. Western red cedar is also known to cause
occupational asthma. Occupational lung cancer
Although cigarette smoking is the primary cause
of lung cancer, some cases can be attributed to
various workplace air pollutants, including
arsenic, coal tar, petroleum, and radium.
Silicosis This oldest of occupational lung
disorders is brought on by inhaling grains of
silica (quartz) in mines, foundries, and
factories. The particles cause gradual scarring
in the lungs that, after many years, may end in
emphysema. Industrial bronchitis Bronchitis
(inflammation of the passages in the lungs) has a
host of causes, including respiratory infections
and persistent exposure to irritants such as
dusts, gases, vapors, cigarette smoke, and even
general air pollution. Because there can be many
causes of bronchitis, both inside and outside the
workplace, it is often difficult to say whether
the problem has its origin in the workplace.
http//www.healthsquare.com/mc/fgmc9013.htm
86
Shavers Disease

• Inhalation of finely divided aluminum and
  aluminum oxide powder has been reported as a
  cause of pulmonary fibrosis and lung damage. This
  effect, know as Shavers Disease, is complicated
  by the presence in the inhaled air of silica and
  oxides of iron. May also be implicated in
  Alzheimers disease.

87
Gout

• The uric acid level in the blood goes up in
  persons with gout. Alcohol is not recommended for
  persons with an elevated uric acid because it
  causes your body to lose water and may increase
  the uric acid levels in the blood.
• In general, foods that cause gout are high in
  fat, which is why dietary recommendations for
  people with this kind of arthritis advise that
  less than 30 of their calories come from fat.
  Proteins with large concentrations of purines
  include meat and dairy products. Fish, like
  mackerel, sardines, oysters, mussels, and
  scallops, should be avoided, as well as red and
  white meat like poultry, pork, and beef.
  Sweetmeats, or organ meat, like kidney, heart, or
  liver, are especially bad for those suffering
  from gout. Even foods related to meat, like
  chicken or beef broth, caviar, and bouillon might
  produce high levels of uric acid.
• Other foods that cause gout are dairy and
  vegetables, because they have lots of purines as
  well. High-fat dairy, like whole milk, ice cream,
  butter, and cheese, must be avoided in favor of
  low-fat dairy, or soy replacements. Spinach,
  mushrooms, cauliflower, peas, and asparagus have
  been shown to be rich in purines. In an unrelated
  food category, lentil beans and yeast increase
  one's chance of gout flaring up. For this reason,
  even beer and alcohol, because they are derived
  from yeast and grains, can increase the
  discomfort of gout.

88
Amyloidosis
Amyloidosis refers to the extracellular
deposition of a protein called amyloid. This
protein deposition can affect multiple organs.
In this picture, we see how amyloidosis can
affect the skin as nodular deposits on the
fingers.
Amyloidosis can cause a patchy, bruised
appearance to the skin. Bruises of the skin
around the eyes are referred to as the
characteristic "pinched purpura".
Three major types of amyloid and several less
common forms have been defined biochemically (1)
AL an N-terminal sequence that is homologous to
a portion of the variable region of an
immunoglobulin light chain, occurs in primary
amyloidosis and with multiple myelom (2) AA
unique N-terminal sequence of a nonimmunoglobulin
protein called AA protein (3) associated with
familial amyloid polyneuropathy, a transthyretin
(prealbumin) molecule that has a single amino
acid substitution.
89
Aging and free radicals
90
Oxidative stress and ageing disproved?
1 December 2008 Diets and beauty products
claiming to have anti-oxidant properties are
unlikely to prevent ageing, according to research
funded by the Wellcome Trust. Researchers at the
Institute of Healthy Ageing at UCL (University
College London) say this is because a key
50-year-old theory about the causes of ageing is
wrong. 'Superoxide' free radicals - oxygen
molecules that have an imbalance of electrons to
protons - are generated in the body through
natural processes such as metabolism. These free
radicals can cause oxidation in the body,
analogous to rust when iron is exposed to oxygen.
Biological systems, such as the human body, are
usually able to restrict or repair this
damage. In 1956, Denham Harman proposed the
theory that ageing is caused by an accumulation
of molecular damage caused by 'oxidative stress',
the action of reactive forms of oxygen, such as
superoxide, on cells. This theory has dominated
the field of ageing research for over 50 years.
But now, a study published online today in the
journal 'Genes and Development' suggests that
this theory is probably incorrect and that
superoxide is not a major cause of ageing. "The
fact is that we don't understand much about the
fundamental mechanisms of ageing," says Dr David
Gems from UCL. "The free radical theory of ageing
has filled a knowledge vacuum for over fifty
years now, but it just doesn't stand up to the
evidence."
91
(oxidative stress, cont.)
Dr Gems and colleagues at the Institute of
Healthy Ageing studied the action of key genes
involved in removing superoxide from the bodies
of the nematode worm C. elegans, a commonly used
model for research into ageing. By manipulating
these genes, they were able to control the worm's
ability to 'mop up' surplus superoxide and limit
potential damage caused by oxidation. Contrary to
the result predicted by the free radical theory
of ageing, the researchers found that the
lifespan of the worm was relatively unaffected by
its ability to tackle the surplus superoxide. The
findings, combined with similar recent findings
from the University of Texas using mice, imply
that this theory is incorrect. "One of the
hallmarks of ageing is the accumulation of
molecular damage, but what causes this damage?"
says Dr Gems. "It's clear that if superoxide is
involved, it only plays a small part in the
story. Oxidative damage is clearly not a
universal, major driver of the ageing process.
Other factors, such as chemical reactions
involving sugars in our body, clearly play a
role." Dr Gems believes the study suggests that
anti-ageing products that claim to have
anti-oxidant properties are unlikely to have any
effect. "A healthy, balanced diet is very
important for reducing the risk of developing
many diseases associated with old age, such as
cancer, diabetes and osteoporosis," he says. "But
there is no clear evidence that dietary
antioxidants can slow or prevent ageing. There is
even less evidence to support the claims of most
anti-ageing products."
92
Progeria
93
Progeria and WernersSyndrome
The cause of progeria (HGPS) is unknown. It is an
autosomal recessive disease, meaning that an
individual carrying a mutation in a single gene
does not show any symptoms. When two individuals
with the mutant gene have a child, that child has
a 1 in 4 chance of inheriting two copies of the
mutation and therefore having the disease. The
autosomal recessive gene mutation causing Werner
syndrome, on the other hand, has been identified
(National Library of Medicine), and cloned. The
Werner syndrome protein (WRN) codes for an enzyme
in the family of enzymes called helicases. These
enzymes are responsible for unwinding the double
strand of DNA in each cell as the DNA is to be
duplicated for cell division. Each strand of DNA
has its own helicase associated with it. Although
the mechanism by which a defect in this enzyme
would cause Werner syndrome is not known, it's
normal counterpart may be responsible for DNA
repair, and thus preventing cancer and cell
defects. http//www.seps.org/cvoracle/faq/progeria
.html