Professional Documents
Culture Documents
Review
Chapters summarized in this work: Anemia Hemostasis Lung diseases Respiratory Failure Renal Diseases Renal Failure Jaundice Pancreas Problems Portal CirculaCon Arrhythmias Cardiomyopathies Valvulopathies
It
is
a
very
fast,
quick
review
of
the
whole
thing
It
is
not
a
complete
work
for
Your
prepara;on,
but
a
useful
pre-exam
lecture
Based
on
Doc.
Jipas
material
and
Robbins
Pathology
Alessandro
MoIa,
UVVG,
3rd
year
1
Anemia
Blood
Components:
Plasma:
55%;
Blood
Cells:
45%
Three
types:
Erythrocytes/RBCs
Leukocytes/WBCs
Thrombocytes/Platelets
Hematopoiesis is the process by which mature blood cells are generated and funcConal, assuming the existence of cells of origin who have a long series of transformaCons and hematopoeCc microenvironment (composed of stromal cells and sCmulaCng factors). Bone marrow is the central component generaCng blood cells: red cells, granulocytes, monocytes, lymphocytes, platelets and hematopoieCc funcCons are proliferaCon, dierenCaCon and cell release into circulaCon. Bone marrow consists of: reCculovascular stroma (with supporCng role, nutriCon and movement of hematopoieCc cells); medullar parenchyma - composed of acCve cells forming islands of hematopoiesis, usually arranged around a trophic cell - "nurse cell." Nurse cells are involved in erythropoiesis (iron stores) in myelopoesis and megacaryopoesis (liberate sCmulaCng factors - e.g.. IL-3). Pluripotent stem cells (PSCs) are the cells of origin of all blood cells.
The RBC life cycle: In the bone marrow, erythropoieCn enhances the growth of dierenCaCon of burst forming units-erythroid (BFU- E) and colony forming units-erythroid (CFU-E) into reCculocytes. ReCculocyte spends three days maturing in the marrow, and then one day maturing in the peripheral blood. A mature Red Blood Cell circulates in the peripheral blood for 100 to 120 days. Under steady state condiCons, the rate of RBC producCon equals the rate of RBC loss. What is anemia?Is a pathological state, accompanied by decrease in: the level of hemoglobin, the quanCty of erythrocytes, per unit of volume of the blood. Result: deciency in the oxygen-carrying capacity of the blood (hypoxia) Hemoglobin = grams of hemoglobin per 100 mL of whole blood (g/dL) Hematocrit = percent of a sample of whole blood occupied by intact red blood cells RBC = millions of red blood cells per microL of whole blood MCV = Mean corpuscular volume If > 100 MacrocyCc anaemia If 80 100 NormocyCc anaemia If < 80 MicrocyCc anaemia RDW = Red blood cell distribuCon width = (Standard deviaCon of red cell volume mean cell volume) 100 ; Normal value is 11-15%; If elevated, suggests large variability in sizes of RBCs Hgb:Women: <12.0 / Men: < 13.5 Hct: Women: < 36 /Men: <41 Symptoms and Clinical ManifestaDons: Decreased oxygenaDon: ExerConal dyspnea, Dyspnea at rest, FaCgue, Bounding pulses, Lethargy, confusion Decreased volume: FaCgue, Muscle cramps, Postural dizziness, Syncope Clinical ManifestaDons: 1. Pallor. 2. FaCgue, weakness. 3. Dyspnea. 4. PalpitaCons, tachycardia. 5. Headache, dizziness, and restlessness. 6. Slowing of thought. 7. Paresthesia. Physiologic Response to Anemia: Increased heart rate, Increased, stroke volume, VasodilaCon, Decreased oxygen anity (right shil in oxygen-hemoglobin dissociaCon curve) 2
Anemias ClassicaCon
Normochromic Hyperchromic
Decreased producDon of red blood cells AplasCc anaemia: ErythropoieCn deciency. Marrow inltraCon- malignancy: injury- infecCons, toxins; NutriConal deciency (iron, proteins); IneecCve erythropoesis(thalassemias); Labs: Low reCculocyte count, variable MCV.
Loss of red blood cells (bleeding, lysis) In blood Loss: ReCculocyte count usually elevated, bone marrow trying to compensate, MCV usually normal to slightly elevated. For Hemolysis: Acquired, Autoimmune process, vessel injury, Inherited RBC defect, ReCculocyte count usually elevated, MCV normal to slightly elevated
NormocyDc Malignancy, Chronic disease, Renal failure, Blood loss, HemolyCc disorders, Hemoglobinopat hies
MacrocyDc Folate deciency, Vitamin B12 deciency, Inherited bone marrow failure, Hypothyroidism, Drug induced, AcCve hemolysis
ComplicaCons in Anemic Syndrome: biochemical changes, hemodynamic changes, respiratory and renal changes, alteraCons of Cssue perfusion, increased producCon of RBCs, immune system abnormaliCes and endocrine changes (hypofuncCons). AplasDc Type Is characterized by Pancytopenia (lowering of all blood cells types). Could be congenital or acquired, has a very low incidence and can be managed by EPO or blood transfusion. CriCcal in blood loss and sepsis. Iron deciency is the most common cause of anaemia, 20% of women (50% of pregnant women) and 3% of men do not have enough iron in the body. DisrupCon of iron metabolism causes anaemia and disturb cytochromes acCvity (cell respiraCon). Iron is obtained through dietary intake (muscle, liver) and iron absorpCon requires the presence of HCl and transferrin. Iron is absorbed in proximal small bowel. It may installs aler small and conCnuous loss of blood, inadequate intake, metabolism disorders or in situaCons of increased needs (pregnancy). Lab ndings: Serum Iron =LOW (< 60 micrograms/dL). Total Iron Binding Capacity (TIBC) = HIGH ( > 360 micrograms/dL). Serum FerriCn= LOW (< 20 nanograms/ mL). IT IS A MACROCYTIC HYPOCRHOMIC CONDITION !!! DestrucCon or hemolysis of RBCs at a rate that exceeds producCon, third major cause of anemia. Can be intrinsic if the problem stands to the hemoglobin itself or extrinsic if caused by external factors (normal RBC). Can be subdivided in: Hereditary spherocytosis, (G6PD) Deciency, ThromboCc Thrombocytopenic Purpura, HemolyCc Uremic Syndrome, Autoimmune HemolyCc anaemia, or can be triggered by infecCons (malaria, babesiosis, sepsis) and traumas (snake bites) Lab ndings: Increased indirect bilirubin, Increased LDH, Increased reDculocyte count, reduced/absent haptoglobin 3
Iron Deciency
HemolyDc
UnderproducCon of RBCs, shortening of RBC survival , 2nd most common cause of anaemia (aler iron deciency anaemia. Generally develops aler 1-2 months of sustained disease. It is a normochromic, normocyCc or hypochromic, microcyCc anaemia, which develops through mulCple mechanisms. Newest name, inamma&on associated anaemia, is more representaCve because it reects pathophysiological mechanisms. Could be secondary (chronic infecCons, collagen diseases, malignancies, elderly paCents). Iron replacement is not necessary. May benet from erythropoieCn supplementaCon. Vitamin B12 and folic acid are important nutrients required in the process of nuclear maturaCon. They are required during erythropoiesis (during DNA synthesis). These anaemias may be caused because of a nutriConal deciency or impaired absorpCon mainly. Impaired DNA synthesis leads to defecCve cell maturaCon and cell division. Nuclear maturaCon delays from the cytoplasmic maturaCon NUCLEO-CYTOPLASMIC ASYNCHRONY. Abnormally large erythroid precursors and red cells. Cobalamin (Vit B12) deciency is formerly known as Pernicious Anemia. Anaemia is normochromic, macrocyCc dened by increasing MCV over 100 -> Macrocytosis is typical in: MegaloblasCc anaemia, Alcoholism, Liver disease. Megaloblas;c anaemia is characterized by nucleo-cytoplasmic asincronism due to deciency in DNA synthesis with normal RNA and protein synthesis (immature nuclei and mature cytoplasm).
Thalassemia EDology: Autosomal recessive geneCc disorder of inadequate producCon of normal hemoglobin weakening and destrucCon of red blood cells. PaCents have defects in either the or globin chain (unlike sickle-cell disease, which produces a specic mutant form of globin), causing producCon of abnormal red blood cells.Found in Mediterranean ethnic groups. Clinical ManifestaDons: AsymptomaCc -> major retardaCon -> life threatening: Splenomegaly, hepatomegaly.
Hemostasis
Four
Stages
2
3
4
1
The process by which the body stops bleeding upon injury and maintains blood in the uid state into the vascular compartment. Process is rapid and localized. It is ruled by: blood vessels, platelets and plasma proteins (coagulaCon, brynolyCc, serine protease inhibitors). And other minor processes like Kinin and Complement systems.
Primary hemostasis: Response to vascular injury (vasoconstricCon), FormaCon of the platelet plug adhering to the endothelial wall, Limits bleeding immediately
Secondary Haemostasis (coagulaCon): results in formaCon of a stable clot. Involves the enzymaCc acCvaCon of coagulaCon proteins that funcCon to produce brin as a reinforcement of the platelet plug (FIBRIN CASCADE). Gradually the stable plug will be dissolved by brinolysis. Clot RetracCon Fibrinolysis prevents excessive thrombus (clot) formaCon. It is acCvated by sCmuli that acCvate the Intrinsic pathway (exposure to subendothelial collagen and the platelet plug). Plasminogen is acCvated and becomes Plasmin, which is responsible for lysis of a clot; as well as inhibiCon of platelet aggregaCon and acCvaCon of cloyng factors in the aected area
They interact with injured vessel wall, interact with each other to produce the primary hemostaCc plug, which is fragile and can easily be dislodged from the vessel wall. Are Small, anucleated cytoplasmic fragments, released from megakaryocytes in the bone marrow. Megakaryocyte proliferaCon is sCmulated by thrombopoieCn (TPO). Normal platelet count is 150-400 x 109/L. Survive 9-12 days. Nonviable or aged platelets removed by spleen & liver. 2/3 of platelets circulate in the peripheral blood; 1/3 are sequestered in the spleen. Spontaneous hemorrhaging occurs when platelet count gets < 10 x 109/L. Adhesion Process Shape Change AggregaDo n SecreDon Damage to endothelium exposes blood to the subepithelial Cssue matrix with adhesive molecules. Platelet receptor GPIb binds to subendothelium collagen bers through von Willebrands factor (vWF).Platelet adherence stops the iniCal bleeding Following vessel injury and platelet exposure to external sCmuli, platelets change shape from circulaCng discs to spheres with pseudopods. Shape change is mediated by an increase in cytosolic calcium. Exposure of platelet membrane phospholipids promotes the assembly of vitamin-K dependent factors on the platelet membrane surface. AcCvated platelets adhere to exposed collagen Platelet-to-platelet interacCon: begins 10-20 seconds aler vascular injury and platelet adhesion. Requires dense granule release from the adhering platelets. Requires Ca++ and ATP. Requires brinogen and brinogen receptors GPIIb and IIIa Secondary aggregaCon begins with platelet secreCon of dense granules, these contain large amounts of ADP that binds to the platelet membrane triggering the synthesis and release of TXA2. The release of large amounts of ADP combined with TXA2 amplies the iniCal aggregaCon of platelets into a large platelet mass 5
Bleeding
Disorders
Platelets
disorders
producCon
destruction (Primary/Idiopathic:
ITP
Acute/Chronic
OR
Secondary:
Drugs,
HIV)
Clinical
signs:
Petechiae,
ecchymoses,
haematomas
Bleeding
from
mucosal
surfaces
(epistaxis,
gingival
bleeding,
hematuria,
melena,
hematochezia,
hyphema)
Prolonged
bleeding
aler
venipuncture
or
minor
surgery
In
theory,
spontaneous
bleeding
as
a
result
of
primary
haemostaCc
defect
could
be
due
to
one
of
three
mechanisms:
vascular
defect,
thrombocytopenia
(most
common)
or
thrombopathia
CloZng
factors
abnormaliDes
Congenital:
Von
Willebrand
disease
(MC
with
minimal
bleeding),
Factor
VIII
Deciency
(Hemophilia
A
or
Classic
Type),
Factor
IX
Deciency
(Hemophilia
B)
Acquired:
Vit.
K
deciency
=Due
to
decient
carboxylaCon
of
factors
II,
VII,
IX
&X;
Oral
anC-coagulant;
Coumarin
derivaCves=
warfarin
inhibit
Vit.
K
factors.
Liver
diseases
synthesis
of
factors.
1.
Thrombosis
of
small,
midsize
vessels
and
organ
failure
2.
Contributes
to
mulCple
organ
failure
in
conjuncCon
with
haemodynamic
and
metabolic
consequences
Severe
bleeding
Vascular abnormaliDes Causes: InfecCons (Meningococcemia, Rickesioses , InfecCve endocardiCs) Drug ReacCons Hereditary hemorrhagic telangiectasia Cushing syndrome Henoch - Schnlein Purpura Scurvy and the Ehlers-Danlos syndrome Amyloid inltraCon of blood vessels DIC= disseminated intravascular coagulaDon Is a state/syndrome which is characterized by accelerated intravascular coagulaCon associated with increased consumpCon of platelets and plasma cloyng factors. CharacterisDc features: acCvaCon of coagulaCon system acCvaCon of brinolyCc system consumpCon of cloyng factors consumpCon of natural inhibitors Thrombocytopenia Its course is determined by: platelet producCon vs destrucCon; brin deposit vs brinolysis; synthesis of coagulaCon factor versus their depleCon 6
and also
Vitamin K deciency
Factors II, VII, IX, X are all K-vitamin dependent. Synthesis of Vitamin K-dependent factors occurs in the liver. Vitamin K is an essenCal cofactor (for carboxylaCon) to acCvate these factors. AnCcoagulant rodenCcides interfere with recycling of Vitamin K, resulCng in rapid depleCon. Proteins C and S are also vitamin K-dependent. Clinical scenario: ObstrucCve jaundice, Fat mal-absorpCon, Broad spectrum anCbioCcs, Hemorrhagic disease of newborn. CoagulaDon tests: ProlongaCon of PT and APTT, normal TT Haemophilia A (factor VIII deciency) is the most common form of the disorder, present in about 1 in 5,00010,000 male births; amount or acCvity of factor VIII; factor VIII = cofactor for acCvaCon of factor X in the coagulaCon cascade. Haemophilia B (factor IX deciency) occurs in around 1 in about 20,00034,000 male births; Clinically= indisCnguishable from Hemophilia A with similar lab ndings; Diagnosis by factor IX levels. Like most recessive sex-linked, X chromosome disorders, haemophilia is more likely to occur in males than females. Haemophilia lowers blood plasma cloyng factor levels of the coagulaCon factors needed for a normal cloyng process. Thus when a blood vessel is injured, a temporary scab does form, but the missing coagulaCon factors prevent brin formaCon, which is necessary to maintain the blood clot. VWFactor is produced by megakaryocytes and endothelial cells, and it circulates in plasma complexed to factor VIII It is important in the formaCon of the primary platelet plug (causes platelets to adhere to subendothelial carClage). Von Willebrand factor's primary funcCon is binding to other proteins, in parCcular factor VIII, and it is important in platelet adhesion to wound sites; it is not an enzyme and, thus, has no catalyCc acCvity. Severe damage to hepatocytes or obstrucCon of bile duct results in variable factor deciencies and/or abnormaliCes in Vitamin K metabolism. Disorders of platelet number and funcCon may occur. PT and PTT can be prolonged. FDP, D-dimer, and brinogen concentraCons may be increased due to reduced clearance of plasminogen acCvators, as well as reduced synthesis of brinolyCc inhibitors. Based on results of coagulaCon tests, may be dicult to dierenCate from DIC. Look to physical exam ndings, chemistry prole changes, and liver funcCon tesCng. Causes: Platelet dysfuncCon or abnormal platelet-vessel wall interacCon due to low Hb (altered blood rheology) Clinical feature: mucocutaneous bleeding. CoagulaCon tests: normal PT and APTT; prolonged skin bleeding Cme
Haemophi lia
HepaDc Diseases
Uremia bleeding
Vessel wall : usually only ecchymoses Thrombocitopenia: platelets ( 80.000; mm3) / Thrombocitosis 7
PT= normal 10 -15 sec (prothrombin Cme)/ PTT= normal; 3-50 sec. (parCal thromboplasCn Cme)
Chronic BronchiDts
Lung
Diseases
Asthma
A.
Intrinsic
asthma
no
environmental
causes
can
be
idenCed
negaCve
skin
test
to
common
airborn
allergens
rather
negaCve
family
history
B.
Extrinsic
asthma
atopy,
geneCc
predisposiCon
IgE,
mast
cells
and
eosinophils
response
to
allergens
C.
OccupaDonal
asthma
sensibilisaCon
of
airways
to
inhalant
chemicals
Intrinsic
Asthma
No
allergic
or
(personal
family)
history
Usually
adult
onset
Olen
follows
severe
respiratory
illness
Symptoms
usually
perennial
More
refractory
to
treatment
Extrinsic
Asthma
Strong
family
history
of
allergies
Usually
onset
at
a
young
age
Other
allergic
manifestaCons
in
paCents
History
of
specic
allergic
associaCon
triggers
(e.g.
pollen,
animal
dander)
CorrelaCon
with
skin
and
inhalaCon
responses
to
specic
anCgens
COPD Emphysema ARDS When does it occurs? Instability of the airways = exaggerated bronchoconstrictor response to a wide variety of sCmuli 1. Acute bronchoconstricCon 2. Swelling of the airway wall 3. Chronic mucus plug formaCon 4. Airway wall remodeling
Early phase response: 30 60 minutes, allergen or irritant acCvates mast cells, inammatory mediators are released (histamine, bradykinin, leukotrienes, prostaglandins, platelet- acCvaCng-factor, chemotacCc factors, cytokines ). Intense inammaCon occurs + Bronchospasm Late phase response: 5 6 hours, it is characterized by inammaCon, eosinophils and neutrophils inltrate, mast cells release histamine and addiConal mediators, Self-perpetuaCng cycle, Lymphocytes and monocytes invade as well, Future aacks may be worse because of increased airway reacCvity that results 8 from late phase response
Chronic
BronchiDs
Presence
of
chronic
producCve
cough
for
3
or
more
months
in
each
of
2
successive
years
in
a
paCent
whom
other
causes
of
chronic
cough
have
been
excluded.
Risk
factors:
cigaree
smoke
or
air
polluCon.
Anatomical alteraDons of lungs: Chronic inammaCon and swelling of the peripheral airways, excessive mucus producCon and accumulaCon, parCal or total mucus plugging, hyperinaCon of alveoli (air-trapping), smooth muscle constricCon of bronchial airways (mild bronchospasm)
Pathophysiology: Chronic inammaDon: Hypertrophy & hyperplasia of bronchial glands that secrete mucus. Increase number of Goblet cells (secrete mucin). Cilia are destroyed Narrowing of airway: StarCng w/ bronchi -> smaller airways: more airow resistance & work of breathing + HypovenClaCon & CO2 retenCon -> hypoxemia & hypercapnea. Bronchospasm oben occurs, as end result: Hypoxemia, hypercapnea, polycythemia (increase RBCs), cyanosis, Cor pulmonale.
Emphysema
Abnormal
permanent
enlargement
of
the
air
space
distal
to
the
terminal
bronchioles.
Accompanied
by
destrucCon
of
bronchioles.
Abnormal
distension
of
air
spaces.
Actual
cause
is
unknown
Pathophysiology: Structural changes: HyperinaCon of alveoli, destrucCon of alveolar & alveolar-capillary walls, small airways narrow, lung elasCcity decreases. Mechanisms of structural change: ObstrucCon of small bronchioles ProteolyCc enzymes destroy alveolar Cssue ElasCn & collagen are destroyed The end result: alveoli lose elasCc recoil, then distend, & eventually blow out. Small airways collapse or narrow. HyperinaCon of alveoli (air-trapping). Decreased surface area for venClaCon There is also a permanent enlargement and deterioraCon of the air spaces distal to the terminal bronchioles; DestrucCon of pulmonary capillaries. And Bronchospasm.
EDology: cigaree smoking, geneCc predisposiCon and other chemicals irritants. ClassicaDon: Centrilobular (most common) Perilobular 9
COPD
Characterized
by
presence
of
airow
obstrucCon.
Caused
by
emphysema
and/or
chronic
bronchiCs.
Generally
progressive
.
May
be
accompanied
by
airway
hyperacCvity.
May
be
parCally
reversible
1. It is chronic 2. It is progressive 3. Mostly xed airway obstrucCon 4. Non reversible by bronchodilators 5. Exposure to noxious agent is a must 6. Two enCCes in COPD namely 7. Chronic BronchiCs 8. Emphysema
Irreversible COPD Why ? Fibrosis and narrowing of the airways Loss of elasCc recoil due to alveolar destrucCon DestrucCon of alveolar support that maintains patency of small airways Reversible Bronchial Asthma AccumulaCon of inammatory cells, mucus, and exudates in bronchi Smooth muscle contracCon in peripheral and central airways Dynamic hyperinaCon during exercise
Respiratory
Failure
Normal
Values
pH
7.35-7.45
PaO2
>70
mmHg
PaCO2
35-45
mmHg
HCO3
22-28
mmol/l
Minute
venClaCon
=
Tidal
volume
X
Respiratory
rate
pH
=
Acidosis
pH
=
Alkalosis
PaO2
=
Hypoxemia
PaCO2
=
Hypercapnia
pH+
PaCO2
R.
acidosis
--
HCO3
pH+PaCO2
R.Alkalosis
--
HCO3
Not a disease but a condiDon. Major threat is the inability of the lungs to meet the oxygen demands of the Cssues. Result of one or more diseases involving the lungs or other body systems. Results from inadequate gas exchange, insucient O2 transferred to the blood (Hypoxemia), inadequate CO2 removal (Hypercapnia) Clinical condiCons in which PaO2 < 60 mmHg while breathing room air or a PaCO2 > 50 mmHg Failure of oxygenaCon and carbon dioxide eliminaCon Acute or Chronic Type 1 or 2 (hypercapnic or Hypoxemic) ObstrucCve or RestricCve Causes: 1. HypovenDlaDon 2. CNS 3. Disorders of peripheral nervous system, respiratory muscles, and chest wall 4. VenDlaDon/perfusion Mismatch (V/Q) 5. Shunt 6. Diusion abnormaliDes ClassicaDon: Hypoxaemic vs. Hypercapnic Acute vs. Chronic ObstrucCve vs. restricCve Clinical Signs and Symptoms:
Compensatory mechanism, clinical signs: Respiratory compensaDon: tachypnea, use of accessory muscles, intercostal recession SympatheDc sDmulaDon: HR , BP, sweaCng Tissue hypoxia: altered mental state, HR and BP (late) Haemoglobin desaturaDon: cyanosis Type 1 = Hypoxemic RF PaO2 < 60 mmHg with normal or PaCO2 Associated with acute diseases of the lung Pulmonary edema (Cardiogenic, noncardiogenic (ARDS), pneumonia, pulmonary hemorrhage, and collapse Type 2 = Hypercapnic RF PaCO2 > 50 mmHg Hypoxemia is common Drug overdose, neuromuscular disease, chest wall deformity, COPD, and Bronchial asthma
In congesDve heart failure: Vascular congesDon: increased capillary blood volume, mild bronchoconstricCon, mild decrease in lung compliance; PaO2 normal or even increased IntersDDal edema: decreased compliance and lung volumes, worsening dyspnea, V/Q abnormality and widened A-a O2 gradient Alveolar ooding: lung units that are perfused but not venClated, shunt physiology with profound gas exchange abnormaliCes, decreased compliance and lung volumes
Hypoxemia: Dyspnea, Cyanosis, Confusion, somnolence, ts, Tachycardia, arrhythmia, Tachypnea (good sign), Use of accessory ms, Nasal aring, Recession of intercostal ms, Polycythemia, Pulmonary HTN, Corpulmonale, Rt. HF Hypercapnia: Cerebral blood ow, and CSF Pressure, Headache, Asterixis, Papilloedema, Warm extremiCes, collapsing pulse , Acidosis (respiratory, and metabolic), pH, lacCc acid
11
Spirometry
DisCncCve
clinical
and
physiological
features
dene:
ObstrucDve
lung
disease:
decreased
FEV1
and
FEV1/VC
RestricDve
lung
disease:
decreased
FEV1.
Normal
FEV1/ VC.
Decreased
Tco.
Total
Lung
Capacity
(TLC)
-
the
total
volume
of
the
lung,
the
volume
of
air
contained
in
the
lung
at
the
end
of
maximal
inspiraCon
Inspiratory
Reserve
Volume
(IRV)
-
volume,
which
can
be
inspired
beyond
a
resul
inspiraCon
Tidal
Volume
(TV)
volume
of
a
single
breath,
usually
at
rest
FuncConal
Residual
Capacity
(FRC)
-
The
amount
of
air
lel
in
the
lungs
aler
a
Cdal
breath
out,
the
amount
of
air
that
stays
in
the
lungs
during
normal
breathing
Vital
Capacity
(VC)
maximum
volume
which
can
be
venClated
in
a
single
breath
Inspiratory
Capacity
(IC)
-
the
maximal
volume
that
can
be
inspired
following
a
normal
expiraCon
Expiratory
Reserve
Volume
(ERV)
volume,
which
can
be
expired
beyond
a
resul
expiraCon
Residual
Volume
(RV)
volume
remaining
in
the
lungs
aler
a
maximum
expiraCon
Forced
Vital
Capacity
(FVC)
-
the
volume
of
air
that
can
forcibly
be
blown
out
aler
full
inspiraCon,
measured
in
litres
Forced
Expiratory
Volume
in
1
Second
(FEV1)
-
the
maximum
volume
of
air
that
can
forcibly
blow
out
in
the
rst
second
during
the
FVC
manoeuvre,
measured
in
liters
FEV1/FVC
(FEV1%)
-
in
healthy
adults
this
should
be
approximately
7580%.
In
obstrucCve
diseases
(asthma,
COPD,
chronic
bronchiCs,
emphysema)
FEV1
is
decreased
because
of
increased
airway
resistance
to
expiratory
ow
and
the
FVC
may
be
increased
(for
instance
by
air
trapping
in
emphysema).
FEV1/FVC
is
decreased
(<80%,
olen
~45%).
In
restricCve
diseases
(such
as
pulmonary
brosis)
the
FEV1
and
FVC
are
both
reduced
proporConally
and
the
FEV1/FVC
value
may
be
normal
or
even
increased
as
a
result
of
decreased
lung
compliance
In
obstrucDve
diseases:
LimitaCon
of
airow
Rate
of
expiraDon
is
slowed
Volume
usually
normal
FEV1,
FEV1/FVC
(Asthma,
COPD)
In
restricDve
diseases:
LimitaDon
of
lung
expansion
Limit
to
both
volume
&
ow
rate,
An
intersCCal
disease
with
inammatory
and
broCc
changes
in
intersCCum/interalveolar
septum
FEV1,
FVC,
FEV1/FVC
normal
(pneumonia,
pneumothorax,
brosis,
pleural,
cardiogenic
12
Tubular
Renal
Diseases
Glomerulopathies
GlomerulonephriDs,
GN,
is
a
renal
disease
characterized
by
inammaCon
of
the
renal
glomeruli.
Impairment
of
selecCve
ltering
properCes
of
the
kidney
leading
to
a
decreased
GFR
Molecules
normally
not
ltered
such
as
consCtuents
of
the
blood,
pass
into
the
urine
and
are
excreted:
Haematuria
(especially
dysmorphic
red
cells):
red
cell
casts
Proteinuria
(may
be
in
nephroCc
range
of
>3.5
g/24hours)
Lipiduria
(glomerular
permeability
must
be
increased
to
allow
the
ltraCon
of
large
lipoproteins)
Primary
conned
to
the
kidney
Secondary
due
to
a
systemic
disease
Clinical
manifestaDons:
Proteinuria
asymptomaCc;
Haematuria
asymptomaCc;
Hypertension
NephroCc
syndrome:
gross
proteinuria,
hyperlipidemia
NephriCc
syndrome:
Oliguria,
Haematuria,
Proteinuria,
Oedema.
Acute
renal
failure:
Oliguria,
loss
of
Kidney
funcCon
-
within
weeks
Rapidly
progressive
renal
failure:
Over
months
and
years
Uremia.
End
stage
renal
failure
NephriDc
Syndrome:
haematuria
is
usually
macroscopic
with
pink
or
brown
urine
(like
coca
cola);
oliguria
may
be
overlooked
or
absent
in
milder
cases
(transient
renal
impairment);
oedema
is
usually
mild
and
is
olen
just
peri- orbital-
weight
gain
may
be
detected;
+/- uid
overload
hypertension
common
and
associated
with
raised
urea
and
creaCnine;
proteinuria
is
variable
but
usually
less
than
in
the
nephroCc
syndrome.
NephroDc Syndrome: Is not a disease but a group of signs and symptoms seen in paCents with heavy proteinuria presents with oedema proteinuria usually > 3.5g / 24hrs (>0.05g / kg / 24hrs at children) serum albumin < 30g/l other features: hyperlipidaemia, and hypercoaguable state GN categories: non-proliferaDve: lack of hypercellularity in the glomeruli; they usually cause nephroCc syndrome. ProliferaDve types: characterised by increased number of cells in the glomerulus (hypercellularity). Usually presents as a nephriCc 13 syndrome. ComplicaDons: Acute/chronic Kidney failure, HBP
Tubulo/intersDDal
lots of dierent diseases of tubules and intersCCum, very diverse aeCologies, pathogeneses and appearances, together they account for signicant numbers of cases of renal impairment. IntersDDal NephriDs, causes: InfecCon, mechanical (obstrucCon), drugs, autoimmune, metabolic (diabeCc, uric), radiaCon, neoplasCc inltraCon Bacterial infecDons: bacterial infecCon of the renal parenchyma causes intersCCal nephriCs. InfecCon without anatomical abnormality seldom produces permanent damage. ObstrucCon (stones, prostate etc) in combinaCon with infecCon can cause progressive disease. Tuberculosis causes extensive destrucCon because of granulomas, brosis and caseaCon. PyelonephriDs: Commonly bacterial (Gram negaCve: E.coli, Proteus, Klebsiella, Pseudomonas, Enterobacter) Risk factors: Anomalies, InstrumentaCon, ObstrucCon, bladder dysfuncCon, reux, Pregnancy Symptoms: pain at the costovertebral angle, fever, chills, malaise, Urine: pyuria, bacteria, Dysuria Natural history: Self-limiCng, recurrent, chronic PolycysDc Renal Disease Adult: Autosomal dominant. Huge kidneys full of cysts. Usually no symptoms unCl 30 years. Associated with brain aneurysms. Childhood: Autosomal recessive. Numerous small corCcal cysts. Associated with liver cysts PaCents olen die in infancy
Acute tubular necrosis (ATN): most important cause of acute renal failure; characterized by acute destrucCon of tubular epithelial cells; most commonly secondary to ischaemia, but can also be due to direct toxic cell damage; potenCally reversible, since tubular cells can regenerate (if given Cme). Types: 1. Ischemic: State of hypoperfusion (shock and reducCon in intrarenal blood ow ) 2. Nephrotoxic (heavy metals, solvents, drugs, anCbioCcs, NSAIDs, diureCcs, medium contrast for radiology, pesCcides) In both types we will nd: tubular cell degeneraCon and death, tubular casts of dead cells & debris, intersCCal oedema & secondary inammaCon, pale swollen kidneys, reversible lesion, destrucCon of tubular epithelium, acute suppression of renal funcCon (urine output > 400ml/day)
Gout, Uric Acid and Renal Disease uric acid calculi, parenchymal deposits of uric acid and tubular obstrucCon with urate can cause renal damage an elevated plasma uric acid does not in itself seem to cause renal damage 1/4 of paCents with gout get uric acid stones 1/4 of paCents with uric acid stones will have gout acute nephropathy with overproducCon of uric acid and kidney obstrucCon with uric acid crystals; can occur following treatment of malignant diseases with cytotoxics, heat stroke or status epilepCcus; treat with uids and prophylaxis with allopurinol; role of uric acid in chronic renal failure is disputed, but does occur with some familial disorders;
Autosomal Dominant PolycysDc Kidney Disease: accounts for 7-10% of people on dialysis. 50% of suerers have renal failure by age 60. Cysts may occur in liver and pancreas but do not usually give problems 14
Renal
Failure
ACUTE
Acute: sudden onset, rapid reducCon in urine output. Usually reversible. Tubular cell death and regeneraCon Chronic: Progressive. Not reversible. Nephron loss (75% of funcCon can be lost before its noCceable)
CHRONIC
Inability of kidney to maintain homeostasis leading to a buildup of nitrogenous wastes Dierent to renal insuciency where kidney funcCon is deranged but can sCll support life Occurs over hours/days Lab deniCon 1. Increase in baseline creaCnine of more than 50% 2. Decrease in creaCnine clearance of more than 50% 3. DeterioraCon in renal funcCon requiring dialysis Anuria no urine output or less than 100mls/24 hours Oliguria - <500mls urine output/24 hours or <20mls/hour Polyuria - >2.5L/24 hours Sudden interrupDon of kidney funcDon resulCng from: - reduced circulaCon: Pre-renal = 55% - disease of the renal Cssue: Renal parenchymal (intrinsic)= 40% - obstrucCon: Post-renal = 5-15% Results in retenDon of toxins, uids, and end products of metabolism Usually reversible with medical treatment May progress to end stage renal disease, uremic syndrome, and death without treatment Types: Pre-Renal or funcConal (hypovolemia, shock, blood loss, embolism, ascites or burns, CV disorder, etc.) Intrarenal or intrinsic/structural (nephrotoxic agents, infecCons, ischemia, etc.) Postrenal or obstrucCve (stones, blood clots, etc.)
Results from gradual, progressive loss of renal funcCon. Occasionally results from rapid progression of acute renal failure. Symptoms occur when 75% of the nephrons are lost, but considered chronic if 90-95% loss of funcCon. Dialysis is necessary D/T accumulaCon of uremic toxins, which produce changes in major organs. Chronic renal failure, or ESRD, is a progressive and irreversible deterioraCon in renal funcCon in which the bodys ability to maintain metabolic and uid and electrolyte balance fails, resulCng in retenCon of urea and other nitrogenous wastes in the blood. Uremia develops and adversely aects every system in the body. ESRD occurs when there is less than 10% nephron funcCon remaining. All of the normal regulatory, excretory, and hormonal funcCons of the kidney are severely impaired. Is stated as the presence of GFR <60 mL/min/1.73 m2 for three months, with or without other signs of kidney damage as described above. Triggers also low GFR, Na and K retenCon, metabolic acidosis and anemia. Causes: DiabeCc Nephropathy Hypertension GlomerulonephriCs HIV nephropathy Reux nephropathy in children PolycysCc kidney disease Kidney infecCons & obstrucCons 15
Jaundice
It is yellowish discoloraCon of: skin, mucous membranes, sclera; due to excess plasma bilirubin
The dierenCal diagnosis for yellowing of the skin is limited. InaddiCon to jaundice, it includes Carotenoderma, the use of the drug, Quinacrine, excessive exposure to phenols. Is not a disease but rather a sign that can occur in many dierent diseases. Normal ndings for bilirubin is 5-17 m mol/l, while clinically obvious results are: 50 mmol/l (2.5mg/dl). Bilirubin is a bile pigment, lipid soluble and is a product of heme metabolism (check the HEME metabolism picture ->) 75% is derived from RBCs. In normal adults this results in a daily load of 250-300 mg of bilirubin. Normal plasma concentraCons are less then 1 mg/dL
Interferences at any one of the points of bilirubin processing described above can lead to a condiCon known as HYPERBILIRUBINEMIA. Causes: In rst 3 -> unconjugated N. Increased bilirubin producCon Reduced bilirubin uptake by hepaCc cells Disrupted intracellular conjugaCon Last 2 -> Conjugated Disrupted secreCon of bilirubin into bile canaliculi Intra/extra-hepaCc bile duct obstrucCon
Types
Pre-HepaDc
(hemolyDc):
excess
producCon
of
bilirubin
(beyond
the
livers
ability
to
conjugate
it)
HepaDc:
a
generalized
liver
(hepatocyte)
dysfuncCon
Post-HepaDc
(obstrucDve):
by
an
obstrucCon
of
the
biliary
tree
16
Pancreas Problems
What is Sphincter of Oddi DysfuncDon? The sphincter of Oddi has three major funcCons: 1) regulaCon of bile and pancreaCc ow into the duodenum, 2) diversion of hepaCc bile into the gallbladder, and 3) the prevenCon of reux of duodenal contents into the pancreaCcobiliary tract. The major physiologic role of the sphincter is the regulaCon of the ow of bile and pancreaCc juice. There are two types of sphincter of Oddi dysfuncCon: 1) papillary stenosis and 2) sphincter of Oddi dyskinesia. Papillary stenosis is a xed anatomic narrowing of the sphincter, olen due to brosis. Sphincter of Oddi dyskinesia refers to a variety of manometric abnormaliCes of the sphincter of Oddi
PancreaDDs!
When the acCvaCon of digesCve proenzymes occurs in pancreaCc duct system or aciner cells, the inammaCon is the result. Oedema or obstrucCon of ampulla of Vater resulCng in reexes Of bile into pancreaCc duct or to acinar cells. Pancreas shows edema & necrosis. (10%-30% mortality rate). The release of digesCve enzymes lead to fat necrosis in the pancreas &peritoneal cavity. ACUTE CHRONIC
Pathophysiology: insult leads to leakage of pancreaCc enzymes into pancreaCc and peripancreaCc Cssue leading to acute inammatory reacCon, Steps: STAGE 1: PancreaCc Injury (Edema, InammaCon) STAGE 2: Local Eects (retroperitoneal edema, Ileus) STAGE 3: Systemic ComplicaCons (Hypotension/shock, Metabolic disturbances, Sepsis/organ failure) AutodigesDon theory: AcCvated enzymes digest cellular membranes, cause proteolysis, edema, intersCCal hemorrhage, vascular damage, coagulaCon & fat necrosis, parenchymal cell necrosis LiberaCon of bradykinin pepCdes, increased vascular permeability, and edema with profound eects on many organs, esp. the lungs SIRS, ARDS, MulCorgan Failure, other distant eects
Pathophysiology: irreversible parenchymal destrucCon leading to pancreaCc dysfuncCon. Persistent, recurrent episodes of severe pain. Anorexia, nausea. ConsCpaCon, atulence. Steatorrhea. Diabetes. Causes: #1- eCology is chronic EtOH abuse (90%) Gallstones Hyperparathyroidism Congenital malformaCon (pancreas divisum) Idiopathic ComplicaDons: Shock & renal failure, hypo Ca, hypoalbuminemia, hyperglucemia, hypoxia. Others are exocrine insuciency (steatorrhea) and endocrine insuciency may result from islet cell destrucCon which leads to diabetes 17
A portal system of veins is one which begins and also ends in capillaries. The portal venous branches ramify in an arterial like paern and end in dilated channels called sinusoids, which are equivalent to systemic capillaries. From here blood drains into the hepaCc venous system. The normal portal pressure is 5-7 mmHg (8-12 cm of water). Portal hypertension is present when the portal vein pressure exceeds 12 mmHg Portal hypertension is a high blood pressure in the portal vein and its tributaries (portal venous system). It is dened as a portal pressure gradient (the dierence in pressure between the portal vein and the hepaCc veins) of 5 mm Hg or greater. PRESSURE ABOVE 40 mm Hg. Causes: 1. INCREASED RESISTENCE: Pre-hepaCc (pre-sinusoid): portal vein obstrucCon, congenital, thrombosis, extrinsic Intra-hepaCc (sinusoid): liver cirrhosis, bilharzial periportal brosis Post-hepaCc (post-sinusoid): Budd-Chiari syndrome (hepaCc vein thrombosis) , Veno-occlusive disease and cardiac problems 2. INCREASED BLOOD FLOW: Arterial-portal venous stula Increased splenic ow: BanCs syndrome or splenomegaly
Portal CirculaDon
Consequences:
Porto-systemic collaterals (caput medusae, oesophageal varices, haemorrhoids). Splenomegaly (congesCve).CongesCon of the whole GIT. Bleeding varices. Ascites. InvesDgaDons: Assessment of liver funcCon tests: (a) Hypoalbuminaemia = the liver is the only site of albumin synthesis. (b) ALT & AST are moderately raised. (c) Prothrombin Cme and concentraCon are disturbed = this test is the most sensiCve liver funcCon. DetecCon of oesophageal varices by opCc bre endoscopy or by baritate swallow (radiology) or duplex technique. DetecCon of splenic sequestraCon and hypersplenism: blood analysis, bone marrow examinaCon and radioacCve isotopes studies Diagnosis of the aeCology of liver disease is performed by immunological test (hepaCCs) or liver biopsy Describes the condiCon of pathologic uid collecCon within the abdominal cavity. Can develops for Increased hydrostaCc pressure, Decreased colloid osmoCc pressure, Increase permeability of peritoneal capillaries, Leakage of uid into the peritoneal cavity or miscellaneous causes. In CirrhoCc ascites it develops because of the portal hypertension, the lymph formaCon, renal abnormaliCes with Na retenCon and water retenCon. Also renal vasoconstricCon increase the probability of ascites (late phenomena). The Serum-ascites albumin gradient (SAAG) is beer discriminant than older measures (transudate versus exudate) for the causes of ascites. ClassicaDon: a. A high gradient ( 1.1 g/dL) indicates the ascites is due to portal hypertension. b. A low gradient (< 1.1 g/dL) indicates ascites of non-portal hypertensive eCology.
Ascites
18
Re-entry
Most
common
mechanism:
short
circuit
that
forms
between
two
pathways
that
are
either
anatomically
or
funcConally
disCnct
Typically:
Path
1:
Slow
conducCon,
short
refractory
period
Path
2:
Rapid
conducCon,
long
refractory
period
Parasystole
Arrhythmias
Trigger
AcDvity
ClassicaCon
Is a benign type of automaCcity problem that aects only a small region of atrial or ventricular cells. 3% of PVCs
Is like a domino eect where the arrhythmia is due to the preceding beat. Delayed aler- depolarizaCons arise during the resCng phase of the last beat and may be the cause of digitalis-induced arrhythmias. Early aler-depolarizaCons arise during the plateau phase or the repolarizaCon phase of the last beat and may be the cause of torsades de pointes
AutomaDcity
Heart
cells
other
than
those
of
the
SA
node
depolarize
faster
than
SA
node
cells,
and
take
control
as
the
cardiac
pacemaker.
Factors
that
enhance
automaCcity
include:
SANS,
PANS,
CO2,
O2,
H+,
stretch,
hypokalemia
and
hypocalcaemia.
Examples:
Ectopic
atrial
tachycardia
or
mulCfocal
tachycardia
in
paCents
with
chronic
lung
disease
OR
ventricular
ectopy
aler
MI
What is an arrhythmia? Any abnormality of the cardiac rhythm is called a cardiac arrhythmia. AbnormaliCes of electrical rhythm: generaCng rhythm, conducCon of the electricity . There are two main types of arrhythmia: Bradycardias: the heart rate is slow (< 60 bpm) Tachycardias: the heart rate is fast (> 100 bpm) Common names per region: Atrial: AF, Paroxs. Supra-Ventricular-Tachycardias or SVT ( AVNRT, AVRT (WPW), MulCfocal atrial tachycardia) Ventricular: VT, VF, Torsades Bradyarrythmia: MedicaCon, AV block, SSS Clinical ManifestaDons: PalpitaCons, Syncope, If going fast enough, can precipitate cardiac ischaemia and chest pain, Cardiac failure, Decreased level of consciousness, Hypoperfusion of all organs, Cardiac arrest. ***I has not insisted on each subtype of AR and ecg ndings, you can nd most of them in my previous review from 1st semester
19
Primary (idiopathic) is a disease of unknown eCology that principally aects the myocardium leading to LV dilaCon and systolic dysfuncCon. Secondary causes include ischemia, alcoholic, peripartum, post-infecCous, viral. Most common of the cardiomyopathies. DilaCon and impaired contracCon of ventricles: Reduced systolic funcCon with or without heart failure Characterized by myocyte damage MulCple eCologies with similar resultant pathophysiology
Dilated
Most rare form of cardiomyopathy. Characterized by broadipose replacement of segments of the free wall of the right ventricle. Exam usually normal. EKG- RBBB may be present. Echo-necessary for diagnosis. Regional wall moCon/funcCon is reduced. Familial and progressive. Predominately found in young adults. Ventricular arrhythmias: cause of young adult sudden death
Cardiomyopathies
Are
a
heterogeneous
group
of
diseases
of
the
myocardium,
associated
with
mechanical
&/or
electrical
dysfuncCon
Arrhythmogenic / others
RestricDve
Hypertrophic
GeneCc
disease
characterized
by
hypertrophy
of
the
lel
ventricle
with
marked
variable
clinical
manifestaCons
morphologic
and
hemodynamic
abnormaliCes.
Most
common
cause
of
death
in
young
people.
The
magnitude
of
lel
ventricular
hypertrophy
is
directly
correlated
to
the
risk
of
sudden
cardiac
death
(SCD)
.
Young
pts
with
extreme
hypertrophy
and
few
or
no
symptoms
are
at
substanCal
long-term
risk
of
SCD.
Vigorous
systolic
funcCon,
but
impaired
diastolic
funcCon,
impaired
relaxaCon
of
ventricles,
elevated
diastolic
pressures.
Least common type of cardiomyopathy. Increased sCness of the myocardium -> impaired diastolic lling. Ventricular volumes are usually normal or reduced. Wall thickness is normal or mildly increased . Systolic funcCon is typically preserved. Usually dilated atria.. Hallmark: abnormal diastolic funcCon Rigid ventricular wall with impaired ventricular lling Bear some funcConal resemblance to constricCve pericardiCs Importance lies in its dierenCaCon from operable constricCve pericardiCs Characterized by: impaired ventricular lling due to an abnormally sC (rigid) ventricle, normal systolic funcCon (early on in disease), intraventricular pressure rises precipitously with small increases in volume 20
Valvulopathies
Valve Stenosis: obstrucCon to valve ow during that phase of the cardiac cycle when the valve is normally open. Hemodynamic hallmark -pressure gradient ~ ow// VA Valve RegurgitaDon: Insuciency, Incompetence, Inadequate valve closureback leakage A single valve can be both stenoCc and regurgitant; but both lesions cannot be severe!! CombinaCons of valve lesions can coexist
Mitral Stenosis
Limited ow into the LV has 3 major sequale: ElevaCon of Lt. Atrial pressure, Secondary RV pressure overload, hemopCsy, Reduced LV ejecCon performance.Due to diminished preload.Tachycardic response to compensate to decreased SV worsens the transmitral gradient. EDology: rheumaDc, infecCve endocardiCs, mitral calcicaCon. Natural history: Progressive, lifelong disease, Usually slow & stable in the early years.Progressive acceleraCon in the later years 20-40 year latency from rheumaCc fever to symptom onset. AddiConal 10 years before disabling symptoms Mortality: Due to progressive pulmonary congesCon, infecCon, and thromboembolism Pure Volume Overload. Compensatory Mechanisms: Lel atrial enlargement, LVH and increased contracClity. EDology: Valvular-leaets (Myxomatous MV Disease, RheumaCc endocardiCs, congenital-clels); Chordae defects; Annulus calcicaCon; Papillary Muscles problems; LV dilataCon & funcConal regurgitaCon or Trauma. Chronic MR deniDon: Backow of blood from the LV to the LA during systole, a Mild (physiological) MR is seen in 80% of normal individuals. Is a narrowing of the aorCc valve opening caused by the failure of the valve leaets to open normally. Concentric LVH then develops due to an increase in LV pressure. Thickening and sCening of the LV in the face of increasing obstrucCon results in increased LVEDP. Result = LAH and diastolic dysfuncCon. In signicant Ao. stenosis, the cardiac output may be fairly well maintained at rest but fails to augment with exercise. EDology: congenital, rheumaCc, degeneraCve or calcic.
AorDc stenosis
DeniDon: Leakage of blood from aorta into LV during diastole due to ineecCve coaptaCon of the aorCc cusps. Combined pressure AND volume overload. Compensatory Mechanisms: LV dilaCon, LVH. Progressive dilaCon leads to heart failure. EDology: InfecCve endocardiCs (majority of cases), AorCc DissecCon of the root of the aorta, Trauma. There is an acute and a chronic subtype.
HTN,
ECG
and
Ischemic
heart
disease
are
not
developed
in
this
review.
You
Beloved
Colleague
May
the
Force
Be
With
You
Alessandro
MoIa,
UVVG,
3rd
year
21