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Tuberculosis
It is an infective granuloma caused by myco-bacterium tuberculosis - What is a granuloma - It is a collection of chronic inflammatory cells with predominating histiocytes.
Epidemiology
- 1.7 billion individuals are infected worldwide, 8-10 million new cases develop each year and 3 million deaths per year. - TB is the 6th leading cause to death worldwide. - The incidence increased abruptly after the increase of HIV infection. - TB is the disease of poverty, crowdening,old age,  and debilitating diseases. - Incidence increases with DM, Hodgkin’s disease, renal failure, malnutrition, alcoholism and immune suppression. - The emergence of drug resistant new strains added to the difficulty in controlling the disease. -T.B bacilli are

Aerobic
Acid fast
Non motile
Do not produce toxins

Mycobacterium
Mode of infection
- Human type by droplet infection from an open, active pulmonary disease. - Oropharyngeal and intestinal lesions are acquired by drinking raw contaminated milk by bovine type of bacilli. This type of infection is greatly reduced by pasteurization of milk.
Pathogenesis of tuberculosis
-Organism is phagocytosed by macrophage which is not able to destroy virulent micro-organism.
In the early phase of primary tuberculosis,
(in the non immunized person) -there's uncontrolled proliferation of bacilli within pulmonary alveolar macrophages with resulting bactremia and seeding of multiple sites.
After 3 weeks of infection
-cell mediated immunity develops. Macrophages process mycobacterial antigen and present it to unstimulated CD4+Tн0 cells. - Under effect of IL-12 secreted by macrophages, CD4+Tн0 cells mature into CD4+Tн1 cells which secrete IFN-γ . - IFN-γ activates macrophages to secrete a group of mediators including:-
1- TNF
-causing recruitment of monocytes, their activation, differentiation to epithelioid cells. -It also causes a.  Increased NO production which generate free radicals able to destroy the micro-org

Arterial Blood Gas Interpretation
Normal Arterial Blood Gas Values*

The Key to Blood Gas Interpretation:
4 Equations, 3 Physiologic Processes

1) PaCO2 equation:
PaCO2 reflects ratio of metabolic CO2 production to alveolar ventilation


Hypercapnia


Hypercapnia (elevated PaCO2) is a serious respiratory problem.  The PaCO2 equation shows that the only physiologic reason for elevated PaCO2 is inadequate alveolar ventilation (VA) for the amount of the body’s CO2 production (VCO2).  Since alveolar ventilation (VA) equals total or minute ventilation (VE) minus dead space ventilation (VD), hypercapnia can arise from insufficient VE, increased VD, or a combination.



Examples of inadequate VE leading to decreased VA and increased PaCO2:  sedative drug overdose; respiratory muscle paralysis; central hypoventilation

Examples of increased VD leading to decreased VA and increased PaCO2:  chronic obstructive pulmonary disease; severe restrictive lung disease (with shallow, rapid breathing)
Clinical assessment of hypercapnia is unreliable
-The PaCO2 equation shows why PaCO2 cannot reliably be assessed clinically.  Since you never know the patient's VCO2 or VA, you cannot determine the VCO2/VA, which is what PaCO2 provides.  (Even if tidal volume is measured, you can’t determine the amount of air going to dead space.)

-There is no predictable correlation between PaCO2 and the clinical picture.  In a patient with possible respiratory disease, respiratory rate, depth, and effort cannot be reliably used to predict even a directional change in PaCO2.  A patient in respiratory distress can have a high, normal, or low PaCO2.  A patient without respiratory distress can have a high, normal, or low PaCO2.
Dangers of hypercapnia
-Besides indicating a serious derangement in the respiratory system, elevated PaCO2 poses a threat for three reasons:

1)  An elevated PaCO2 will lower the PAO2 (see Alveolar gas equation), and as a result lower the PaO2.

2)  An elevated PaCO2

The Circulatory Shock
It is failure of the peripheral circulation.

Or

Inadequate tissue perfusion with blood due to decreased cardiac output and arterial blood pressure.
Types of circulatory Shock
1- Hypovolemic Shock

2- Cardiogenic (obstructive) shock

3-Low resistance (distributive) shock


Hypovolemic Shock


-It is characterized by: hypotension, rapid pulse, cold pale skin, rapid respiration, intense thirst, and restlessness or mental dullness.

-The volume of the circulating plasma is decreased

↓

The mean circulatory pressure falls

↓

Venous return decreases
↓

Cardiac output decreases

↓

Arterial blood pressure drops.
Causes of hypovolemic shock
1- severe hemorrhage

2- severe trauma leading to damage of muscle and bone. There is extensive hemorrhage in the damaged tissues

3- severe burns. Large volumes of plasma are lost

4- loss of large volumes of extracellular fluid as in excessive vomiting, sweating and in severe diarrhea

Hemorrhage and hemorrhagic shock


-Hemorrhage is loss of blood from the circulatory system.

-It may be external or internal.  The latter is dangerous because death may occur before diagnosis
Effects of hemorrhage
This depends mainly upon two factors:

1-The rate with which the loss occurs:

-gradual small loss

-sudden large loss

2-The amount of blood lost:

-less than 30%

-more than 30%
Compensatory physiologic mechanisms
1-Immediate compensatory mechanisms

2-Delayed compensatory mechanisms
1- Immediate compensatory mechanisms
I. The drop of arterial blood pressure and central venous pressure

→ decrease the rate of discharge of impulses from the arterial and atrial mechanoreceptors

→ stimulation of the pressor area and inhibition of the depressor area.

This will lead to the following:

1-stimulation of VMC. There will be increased sympathetic discharges to:

a- arterioles except  that of brain and heart

b-Veins

→ Raise the ABP

2-Stimulation of the cardiostimulator center and inhibition of the ca

First Aid of Poly Traumatized Patient
Incidence: Egypt 2004

26 000 motor care accident.
23 000 injured patients.
6 000 dead cases.
5 billion EP loses.

-Trauma is the (neglected disease) of modern society.

-It is the number one killer under the age of 40 years and the 4th  cause of death in all ages.
Trauma Categories
-Those with injuries that are rapidly fatal (5%) -Death is inevitable

-Stable patients (80%) -They need little expertise

-Those with life threatening injuries and required urgent medical  attention (15%) - They need more expertise

Assessment:
-Usually assessment & treatment are going concurrently.

-Requires intensive monitoring during transport, in emergency department, in intensive care unit & in OR.

-Rapid clinical assessment may provide some clues to the cause.

-Pulse, Blood Pressure, Respiratory rate & treatment.

-Blood Sample for: Hb, Ht, urea, electrolytes & cardiac enzymes.

-Blood Grouping & cross matching

-Blood culture if sepsis is suspected.

-Urine output documented hourly through a catheter.

-ECG monitoring nCVP: Rt. ventricular Bl.P

-PAWP: Lt. ventricular function

-Blood gases

-Blood lactate
Management: 3 distinct occasions
-Immediate measures at the scene of accident.

-Transportation

-Emergency room care
1) Immediate measures

When first seen
-The victim should be

Handled as if severe injury has occurred.
Protected from further trauma
Treated by trained personnel.


Care for Shock:
-Keep the victim laying down (if possible).

-Elevate legs 10-12 inches… unless you suspect a spinal injury or broken bones.

-Cover the victim to maintain body temperature.

-Provide the victim with plenty of fresh air.

-If victim begins to vomit - place them on their left side.

-Call 123.
5 Q ?
1)Is the victim breathing ?

2)Is there a pulse or heart beats ?

3)Is there gross external or internal bleeding?

4)Is there any question of spine injury ?

5)Is there any obvious fractures ?
CARDIOPULMONARY RESUSCITATION CPR ABC

Regional Circulation 2
4) Cerebral Circulation
Cerebral blood flow
-In normal adult the brain weights 1400 gm and receives 750 ml blood /min (14% of cardiac output).

-In children cerebral blood flow is nearly double  it's value in adult and it falls to the adult level at puberty. The sex hormones are responsible for this drop.

-Adequate blood supply to the brain is essential.

-Arrest of cerebral circulation more than 5 seconds is followed by loss of consciousness .

-And more than 3minutes>>>>irreversible damage of the grey matter of the  cortex.

-Blood flow of the grey matter is about six times that of the white matter.

-It is enclosed within a solid structure (skull)

-This render the volume of the brain ,blood and cerebrospinal fluid to be constant at any time.

-Is regulated to maintain constant cerebral blood flow sufficient for the metabolic need of the brain.

-Blood flow increases in active  area and decreases In  the inactive one. i.e change in regional blood flow.

-Glucose is the main source of energy in the brain.

-Brain tissues is very sensitive to hypoglycemia and hypoxia.

-The brain is the least tolerant organ to ischaemia

-Interruption of cerebral blood flow for even 5 sec may lead to fainting (syncope)

-The brain represents ~ 2.5% of TBW

-Receiving ~ 15% of Total CO

-The AV O2 difference is~13Vol%

-The cerebral BF is tightly coupled to O2 consumption

-The brain is enclosed within the rigid cranium

-Thus, the volume within the cranium must be kept constant

-So, an increase in arterial vascular volume with arterial dilatation at one site must be associated with a decrease in another site

-Maintenance of Cerebral BF is ensured by a balance between mean arterial pressure (MAP) & intracranial pressure (ICP)

-This balance or difference is cerebral perfusion pressure (CPP) = 80 mm Hg



Cerebral blood vessels

-The cerebral arterial blood is provided from:

2 internal carotid arteries.
2 vertebral arteries unit together>>basilar a

Central Venous Pressure (CVP) & Jugular Venous Pulse (JVP)
You Know


•Venules & Veins are the reservoirs of blood (capacitance vessels of the body)

•Change in venous blood volume & venous pressure can alter CO by affecting right atrial & ventricular preload


Veins
•Veins are more distensible than arteries (thinner muscle layer)

•Many veins have one way valves directing blood towards heart

•The venous blood flow from lower part of the body to abdominal veins is aided by contraction of lower limbs muscles (skeletal muscle pump)

•The venous flow from big abdominal veins to thoracic veins (then to heart) is aided by inspiration (which increases intrathoracic negativity & compress abdominal veins)
Venous Pressure
•Venous Pressure generally refers to the average pressure within venous compartment of circulation

•The mean venous pressure is ~2mm Hg compared to a mean arterial pressure of ~ 90-100 mm Hg

•This low pressure is due to:

-drop of pressure from arterioles to capillaries

-The highly compliant character of veins (can accommodate large volume without great change in pressure)
Normal values of Venous Pressure at Different Body Points
•Hydrostatic Indifferent Point (HIP):
a point about 5-7 cm below diaphragm where venous pressure is ~ 10 mm Hg either on standing or recumbence.
Normal Values of VP

1) Central Venous Pressure (CVP)
•CVP: is the pressure in the thoracic vena cava near the right atrium

•It is important because it determines the filling pressure of right ventricle & consequently the ventricular stroke volume; thus reflecting cardiac function

•Normally, ranges from 2mm Hg (standing) to 4.6 mm Hg (recumbent)
Factors Affecting CVP
•Cardiac output

•Respiratory Activity

•Contraction of Skeletal muscles (esp. leg & abdominal muscles).

•Sympathetic Vasoconstrictor tone

•Gravity

- All these affect CVP by either changing venous blood volume or venous compliance

-Thus, CVP α ∆Vv/ ∆Cv
CVP is increased by:
1.

Hemostasis
Definition
Stop of blood loss after blood vessel injury.

A series of changes occur to stop blood loss including:

A- Vascular spasm

B-Formation of a platelet plug

C-Formation of a blood clot
1- Vascular spasm
It occurs immediately after blood vessel injury
Mechanism:
Nervous reflexes

Local myogenic contraction

Release of chemical substances
Importance of vascular spasm
1-It reduces blood loss from the ruptured vessels.

2- If the injured blood vessel is very small it can stop bleeding completely.
2- Platelet plug formation
Platelets form a mechanical plug to seal the vascular injury.

- If the injury is small, it can stop bleeding.

- If the injury is large, a blood clot is needed.
Mechanism of platelet plug
a-adhesion

Adhesion of platelets to the exposed subendothelial collagen.

b-activation

Adhesion of platelets initiates platelet activation. Platelets swell, develop pseudopodia and become sticky and secrete their granules mainly ADP and thromboxane A2.

c-aggregation

ADP and Thromboxane A2 activate the nearby platelets making them more sticky and adhere to the already adhered platelets.

d-plug formation



Physiological significance

1-If the damage is small the plug can stop bleeding.

2-Extremely important in closing the minute ruptures that occur thousands daily.

3-It does not occlude the circulation.

Clinical applications

Salicylates (aspirin) can inhibit the thromboxane-A2 and so is used commonly as antiplatelet drug.
3- Blood clot formation
- Within 4-8 minutes after rupture of a vessel, the entire opening is filled with clot especially if the opening is not too large.

In the blood, a balance between 2 groups of substances:

1-Coagulation factors.

2-Anticoagulation factors

However, the anticoagulation factors predominate under normal conditions
Clotting factors
They are mostly plasma proteins especially beta globulin type.

They are mostly proteolytic enzymes present in the blood in the inactive state.

They are designated by nam

Why Blood is the Gift of Life?
•No other substitute for blood

•Human Blood is the only substitute for those who need blood
Do U Know?
•Transfer of blood was known since 2 hundreds  years but it only became safer

•Since 1901 when the Austrian Karl Landsteiner who discovered blood groups

•For his discovery, Landsteiner was awarded NOBEL PRIZE in Physiology 1930
Why Blood Grouping is a prerequisite for a safe Blood Transfusion?
•Blood groups depends on presence or absence of certain protein molecules called antigens & antibodies

•So far, more than 20 genetically determined blood groups are known

•However, the most important for blood transfusion are ABO & Rh systems
ABO System
•Is classified into A, B, AB & O according to presence of certain glycoprotein antigen (agglutinogen) on surface of RBCs

•Whereas, in plasma certain non corresponding antibodies (agglutinins) exist

•Presence of agglutinogen with its corresponding agglutinin will induce Ag-Ab reaction (agglutination)



•Plasma agglutinins: Anti-A & Anti B are of IgM type that usually do not cross placenta

•They are naturally occurring because they are formed without previous exposure to foreign blood cells

•At birth, their level is almost zero but start to increase reaching maximum at 8-10 years

•Used for determination of blood groups • •
Rh System
•Rh-positive person (Rh+): with Rhesus antigan (D, C, E) present on surface of his RBCs (D is the most antigenic)

•(Rh-)person:  no antigen on RBCs

•No antibodies exist in plasma without prior exposure to antigen

•Anti-D (antibodies against D antigen) is formed in (Rh-) when he receives Rh+ blood for 1st time



•On a 2nd exposure to Rh+ blood, previously formed anti-D will agglutinate with donor RBCs (sever Ag-Ab reaction) causing haemolysis of RBCs

•Anti-D antibodies are IgG that can cross placenta

•Therefore, if an Rh- mother is exposed to some of her foetus Rh+ blood (during birth process) will for

Thrombosis
It is the process of thrombus formation.
Thrombus
-It is a compact mass formed of the circulating blood elements within the cardiovascular system during life.

-Is a solid mass formed of blood elements inside the cardiovascular system during life
Predisposing factors for thrombosis:-
Three main factors (Virchow’s triad)

1- Endothelial damage (dysfunction).

2- Change in the pattern of blood flow (stasis or turbulence).

3- Changes in composition of blood ( blood coagulability).


Thrombus
Is a solid mass formed of blood elements inside the cardiovascular system during life
Predisposing factors for thrombosis:-
1) Endothelial damage (dysfunction)


2) Change in the pattern of blood flow (stasis or turbulence).


3- Changes in composition of blood ( blood coagulability).
Increased concentration of coagulation proteins or reduced concentration of natural anticoagulants. This change may be hereditary ,acquired or immune mediated
A- Hereditary:-
* About 5-10% of all people have some genetic defect predisposing them to thrombosis.

* These include congenital deficiency of antithrombin III, protein C and protein S and mutation in the gene encoding factor V.
B- Acquired :-
* Tissue damage….increase the production of thromboplastin and other procoagulants.

* Chronic infection…. Liver produces excess fibrinogen (one of acute phase reactants).

* Estrogen containing oral contraceptives….increase the production of prothrombin and fibrinogen.

*Tumors…..increased release of thromboplastin.
C- Immune mediated thrombosis
*Heparin-induced thrombocytopenia

-seen in 5% of patients with chronic use of high molecular weight heparin.

- Caused by antibodies to the complex of heparin and platelet factor 4 → Antibodies cross reacts with platelets and endothelial cells → platelet and endothelial injury → thrombosis.
Morphology of thrombi
Large thrombi formed in veins, arteries and heart of living patients have typical features that distinguish them from

BLOOD
Composition:
Suspension of cells in a complex liquid (Plasma).
Plasma:
•H2O+ Organic molecules + Mineral Salls.

•After coagulation (- Fibrinogen)= Serum
Blood Cells:
•R.B.C

•W.B.C

•Platelets
Origin:
Site:
•In the embryo (liver, Spleen, Bone marrow)

•After birth (only in the Bone marrow)

•Lymmphoid tissues (B.M. , L.N., Spleen , Payer`s Patches)
EXAMINATION OF THE BLOOD
COMPLETE BLOOD PICTURE(C.B.C)
A.Quantitative Examination:
1- Quantitative Exam. Of the RBCs with its constituents:




A- R.B.Cs no./mm:



B- Hematocrite :( Relative Volume of R.B.Cs in the blood)

- By centrifugation of a small column of blood in a standard tube:



C- Hb. Content of 100 cc blood



D- mean Corpuscular Volume:



Normal : 85-95 N

•If    83  indicates Macrocytosis

E- Mean Corpuscular Hb. Conc.:



Normal: 0.32 – 0.36 (32%-36%)  (Normochromic)

•If >   32  indicates Hypochomic

•If =8 gm in regenerative anaemia ( e.g, haemolytic or post Hgic)—reticulocytic count must be < 100.000. if > 100.000 this means aregnerative. i.e. (Hypoplastic or apastic ) anaemia.
2-Quantitive Exam. Of WBCs


N.B. In adults .

•<   11.000 indicates leucocytosis

•>   4.000 indicates leucopenia.
3- Quantitative Estimation of Platelets:
Normal : 15.0.000-040.000/ mm3

>  150.000 indicates thrombocytopenia

< 450.000 indicates thrombocytosis.
B- M

HYPERTENSION
PRIMARY  AHT

SECONDARY  AHT e.g. PHEOCHROMOCYTOMA & CON  Syndrome
HYPERTENSINOGENICS
•NEURAL  &  BEHAVIOURAL

•HUMORAL

•ENDOTHELIAL

•DIETARY


THERAPEUTIC MARKERS


•BIOCHEMICAL

•DEMOGRAPHIC

•INDIVIDUAL

•GENETIC


THERAPY OF HYPERTENSION
•LIFESTYLE  MODIFICATION

•DRUG THERAPY
ANTIHYPERTENSIVES
Commonly used:

•Diuretics

•B.B.

•Ca. Channel blockers

•A.C.E.I.

•AT II receptor blocker
Others:
•Direct  VD

•Central

•Alpha blockers

•Alpha+Beta  blockers

•Adr. N. Blockers

•5-HT antagonists

•Gang. Blockers

•K Channel oppeners
DIFFERENTIAL DRUG THERAPY
•CHILDHOOD

•PREGNANCY

•ELDERLY

•BLACKS

•OBESE

•RESISTANT  HYPERTENSION


1- DIURETICS


LOOP   DIURETICS(Furosemide)

DISTAL  TUBULE  DIURETICS (Spironolacton)
Main Adverse Effects of Diuretics:
•Hypovolaemia

•Hyponatraemia

•Hypokalaemia

•Hyperkalaemia with Aldosterone antagonists (Spironolacton)
2-BETA-BLOCKERS


ANTIHYPERTENSIVE MECHANISMS OF BB



BETA  BLOCKERS  MECHANISM

•-ve chronotropic  & inotropic  effects

•Suppression  of renin release

•Decreases the  central sympathetic outflow

•Gradual resetting reconditioning of baroreceptors

•Some B.B. are VD e.g. Dilevalol & Celiprolol

•May alter vascular PGs

•Decrease adrenergic release by presynaptic B2 block

ADVERSE EFFECTS  & PRECAUTIONS

HT.F

BRADYCARDIA

HYPOTENSION

BRONCHOSPASM

#  INSULIN

PERIPHERAL ISCHEMIA

HYPERKALAEMIA IN….

NIGHTMARES
DEPRESSION
Inc. TRIGLYCERIDES
Dec. HDL

DISEASE  DETER.  WITH SUDDEN ….
Contraindications &Precautions CCBs:
•HF

•A.V. block

•Sick sinus S.

•WPWS

•Low BP

•Unstable angina (Nif.
CALCIUM CHANNEL BLOCKERS

Adverse  effects of CCBs:
•HF aggravation

•Angina  ,, (Nif.)

•A.V. block

•Decrease glucose tolerance

•↓ flushing, nasal cong. & tinitus.
Contraindications &Precautions CCBs:
•HF

•A.V. block

•Sick sinus S.

•WPWS

•Low BP

•Un

Blood cells

Blood composition
Red blood corpuscles
Role of liver and spleen in the formation and destruction of erythrocytes
Hematopoiesis


Introduction
Blood is a fluid which is continuously circulating inside the blood vessels by the pumping action of the heart, acting as a link between various cells and systems of the body
Blood composition
The blood consists of a fluid part representing 55% of its volume which is the plasma and cellular elements representing 45%

The cellular elements are :

A-The red blood cells

B-White blood cells

C-Platelets
Red Blood Corpuscles
Shape and size
These are non-nucleated circular biconcave discs which are about 2.2 microns thick, 7.2 microns in diameter and about 90 cubic microns in volume.

They contain the red respiratory pigment hemoglobin




Structure of erythrocytes
- The RBCs are surrounded with a plastic semipermeable membrane which is lipoprotein in nature. This allows the changes in size of the corpuscles and help them to be squeezed through the narrow capillaries



-The most important constituent of the red blood corpuscles is hemoglobin. Its concentration inside RBCs is 34%.

-The chief cation inside is potassium.

-The corpuscles contain also carbonic anhydrase enzyme the which plays an important role in carbon dioxide transport
Hemoglobin
-It is made of four subunits. Each subunit is formed of heme and a polypeptide .

-Heme is an iron protoporphyrin. The latter is formed of glycine and succinyl-Co A.

-In each molecule of Hb there are four atoms of iron and two pairs of polypeptide called collectively globins.

-Each gram of hemoglobin unites loosely with 1.33 ml oxygen.


Hemoglobin molecule

Normal Hemoglobin content

-16 gm% in adult males

-14 gm% in adult females

-It is estimated by Sahli apparatus.
Types of Hemoglobin

-The Hb of normal adult is called Hb A.

-Slight changes in its polypeptide chains produce abnormal types of Hb

-The commonest abnormal Hb include:

a-Hb A2 : It is harmless and r

Arterial blood pressure

Normal values
Factors affecting
How to measure
Regulation
The arterial Blood Pressure
It is the lateral force exerted by the moving column of blood on the lateral wall of arteries


Systolic blood pressure
-This is the maximum pressure created inside the arteries during ventricular systole due to rapid ejection of blood into the aorta.

-It normally ranges between 90 and 140 mmHg at rest.


Diastolic blood pressure
It is the minimum pressure which remains inside the arteries at the end of ventricular diastole.

Diastolic blood pressure is normally between 60 and 90 mmHg at rest.

Pulse pressure
It is the difference between the systolic and diastolic blood pressures which equals about 40 mmHg.
The mean systemic ABP
This is the average pressure in the systemic arteries throughout the cardiac cycle.

It is calculated as:

Mean arterial blood pressure = diastolic pressure + 1/3 pulse pressure

Importance of ABP
1- It maintains sufficient pressure to keep the blood flowing.

2- It provides enough hydrostatic pressure inside the capillaries essential for the formation of interstitial fluid, urine, …. etc

Physiological Variations in ABP
1-Age

2-Sex

3-Race

4-Body built

5-Meals

6-Gravity

7-Emotions

8-Sleep

9-Exercise

10-Respiration
Measurement of ABP
-Direct measurement by cannulation of a large artery.

-Indirect measurement by Sphygmomanometer:

A-The palpation method

B-The auscultatory method


Factors that determine and maintain the ABP
1- The cardiac output
C O P  =  S V  X  H R

-Changes in the stroke volume with the HR constant affect the systolic more than the diastolic pressure.

-Changes in the HR with constant SV affect the diastolic more than the systolic blood pressure
2-The peripheral resistance
Factors that determine the PR:

PR  =  VL/r4

A-The diameters of arterioles (r)

B-Viscosity of blood (V)

C-Length of the blood vessels (L)
Regulation of diameter of arterioles
-The arterioles represent the main peripheral

Hypertension
It is persistent elevation of blood pressure above 140/90

-It may be primary (essential) or secondary.

- Each type may be benign or malignant (according to severity).

- Each type can affect many organs the most important of which are…heart, blood vessels, kidney, brain and retina
Secondary hypertension
Secondary to….
1- Renal…renal ischemia.

2- Endocrine… hyperaldosteronism, pheochromocytoma, hyperthyroidism.

3- Neurogenic.. Brain tumors or encephalitis.

4- Coarctation of the aorta.

5- Stress, psychogenic, post-operative.
Primary (Essential) hypertension
It is hypertension of unknown etiology but there are certain predisposing factors

a. Familial predisposition.

b. High salt intake

c. Cigarette smoking, alcoholism.

d. Emotional stress.

E. Lack of exercise.
Pathogenesis of hypertension
MEAN ARTERIAL BLOOD PRESSURE

= CARDIAC OUTPUT X TOTAL PERIPHERAL RESISTANCE

BP= C.O  X TPR




Effects of hypertension
Heart changes.

Vascular changes

Renal changes.

Brain changes.

Retinal lesions.

Causes of death ???
I- Benign Hypertension
1) Heart Changes
-With increasing pressure, the left ventricular myocardium undergoes hypertrophy.

- With hypertension, the severity of atheromatous lesions are usually more severe.

- Coronary blood flow may be insufficient leading to ischemic heart diseases


Left ventricular hypertrophy
Left ventricular failure is a common complication of hypertension


2) vascular changes
1- Aorta
- Hypertension predisposes to development of severe atheroma, abdominal aortic aneurysms and dissection.





Aortic aneurysm

- Atherosclerotic aortic aneurysm affecting the abdominal aorta.

- This aneurysm is complicated by a thrombus.

- Other complications include rupture and pressure on other structures.


2- Small Blood vessel changes

Benign arteriolosclerosis
Benign arteriosclerosis
Atheroma is severe


hyalinosis and elastosis

Both changes below lead to narrowing of the blood vessels and ischemia of the affected par

HEART  METABOLISM IN  ISCHAEMIA

TYPES  OF ANGINA

TREATMENT  OF  ANGINA
•GENERAL MEASURES & LIFESTYLE  MODIFICATION

•DRUG THERAPY

•SURGERY
GENERAL  MEASURES
•LIFE  STYLE  MODIFICATION

•CORRECT  OBESITY & REDUCE  FAT INTAKE

•TREATMENT  OF PREDISPOSING FACTORS
DRUGS
DURING  ACUTE ATTACK ( Relief of pain)
•Short  acting  nitrites & nitrates

•Sedative  &  analgesic
IN  BETWEEN:
•Long  acting  nitrates or Nicorandil (K Channel activator)

•B.B. (non selective) or CCB (e.g. Diltiazem, Amlodipine)

•Cytoprotective  drugs

•Antiplatelet (e.g.Aspirin)

•Cholesterol lowering drug (e.g. Statin)
ORGANIC  NITRITES  &  NITRATES (Are esters of nitrous acid & nitric acid)
PH.K.  Of  nitrites  &  nitrates

•Readily  absorbed

•High 1st pass  of  Dinitrate  & Tetranitrate

•Low 1st pass  of Mononitrate

•Renal  excretion



Antianginal mechanism of Nitrites:

1. Coronary  dilator

2. Venodilator mainly Cardiac Output  &  Work  decrease
CORONARY  DILATOR  MECHANISM  OF  NITRITES  & NITRATES

PHARMACOLOGICAL  EFFECTS
CVS:

•Coronary  dilator Venodilator mainly

•Cardiac Output  &  Work  decrease Tachycardia

•B.P.  Decrease  (with high dose rapid adm.)

Smooth muscle  relaxation

Tachypnea

Methaemoglobinaemia
USES  OF  NITRITES
•Angina   pectoris  ( mechanism  ? ) / CHF M / Infarction

•Biliary  Colic

•Uterine Constriction  ring

•Cyanide  poisoning  ( mechanism  ? )



ADVERSE  EFFECTS  OF NITRITES

•Throbbing  headache

•Postural hypotension, syncope

•Tachycardia

•Flushing

•Methaemoglobinaemia  (rarely) •Tolerance   ???

Nitrite   tolerance

•More  with  mononitrate

•Mechanism:

(1) Depletion  of SH  donors

(2) Reflex  VC  &  Sod.  Retention

•Prevented  by:  nitrate-free interval (12hrs)

PRECAUTIONS  OF  NITRITES

•Start by the smallest  dose

•Stop gradually

•Consultation:15  min  failure of subli

CLINICAL PRESENTATION


Artherosclerosis


Ischemic Heart Disease


Angina Pectoris


Myocardial Infarction


Atherosclerosis
- The commonest arterial disease characterized by formation of fibro fatty plaques, formed of a deeper soft part and a hard sclerotic fibrous cap


Epidemiology….
a. Most common cause of morbidity caused by vascular disease.

b. Highest incidence in Finland, Western Europe, USA and Canada.

c. Increased incidence with advanced age.

d. More in males than females up to the age of menopause.
Risk factors


- Constitutional risk factors.

- Hard risk factors

- Soft risk factors
Constitutional risk factors
Age
The number and severity of atheromatous lesions increase with age.
Sex
more common in males than females up to the age of 55 years. Estrogen has a protective effect ??
Familial predisposition
Hard risk factors
- Hyperlipidemia
-Increased level of cholesterol and LDL is associated with increased risk of atherosclerosis.
- Familial hyperlipidemia (especially types II and III) is associated with increased risk of atherosclerosis.
- On the contrary, HDL has a protective effect against atherosclerosis.
- Hypertension
- Diabetes mellitus
due to associated hyperlipidemia
- Cigarette smoking
Soft risk factors
- Exercise
Reduces the incidence of atherosclerosis and death from ischemic heart diseases
- Overweight
atherogenic diet high in animal saturated  fatty acids and cholesterol.
- High complex sugars in diet.
- Low vegetables and fish.
- Stress and personality
Personality A
Pathogenesis of Atherosclerosis



•Current concept (Reaction to injury formulation)
Injury (or dysfunction) of arterial endothelium
leads to…
a. Entry of monocytes and lipids to subendothelim.
b. Platelet adhesion and aggregation.
c. Release of mitogenic factors from platelets and macrophages…..proliferation and migration of smooth muscle fibers.
d. Monocytes and smooth muscle cells engulf lipid and cause lipid deposition into the lesion.




Pathology of athe

HEART
-70ml/beat, 7200 l/day

-35 million beats /year, 2.5 billion beats/life

The work of the heart in one life is equivalent to lifting 30 tons to the Mount Everest

Myocardial O2 Demand
• The cardiac muscle always depends on aerobic oxidation of substrates even during heavy exercise

•Therefore, The cardiac muscle has the highest O2 uptake (VO2) compared to other tissues of the body(12-15 volume%; 7-9mlO2/100gm/min)

•This is achieved by a dense network of capillaries, all is perfused at rest (no capillary reserve)

& by maximal extraction of O2 from RBCs (almost no O2 extraction reserve)
What determines Myocardial O2 Demand?
•The direct factor is Left Ventricular Work (ventricular contraction to eject blood)

•VO2 is increased by an ↑ in;

1.Afterload

2.Contractility

3.Heart rate

4.Preload*
How this affects Coronary blood flow?
•The fact that there is no O2 reserve for cardiac muscle makes the increase in blood flow is the alternative for an extra need for O2

•Thus, any restriction in flow → increased risk of tissue damage

•The increased flow is due to functional hyperaemia which explains the major role of local metabolic factors in regulating coronary circulation
Physiological Anatomy of Coronary Circulation


•Coronary Blood flow is provided by Lt. & Rh coronary arteries originating from root of aorta behind the aortic cusps

•These 2 large arteries give rise to

-Large Epicardial Coronary Arteries (EPCA) encircling the surface of heart

-Intramyocardial Coronary Arteries (IMCA) penetrating into deeper layers of heart

•The Coronary arterial tree gives rise to millions of capillary blood vessels that nourish the myocardium.

•The coronary arteries are having small anastomotic connections (end arteries)

•Therefore, risk of tissue damage is greater if arterial occlusion occurs.
•Coronary Venous drainage:
- Coronary sinus draining ~90% of Lt ventricle into Rh atrium

- The bsian veins +arterioluminal veins draining rest of m

CLINICAL MANFESTATIOS OF ISCHEMIC HEART DISEASE


SIZE OF HE PROBLEM


ATHEROTHROMBOTIC CORONARY HEART DISEASE


RISK FACTORS FOR IHD


CLINICAL PRESENTATION


DIAGNOSIS AND INVESTIGATIONS


THERAPY


PREVENTION


SIZE OF THE PROBLEM
IHD is now the leading cause of death worldwide, and it is expected that the rate of IHD will accelerate in the next decades, contributed to by;

1.aging of population

2.Alarming increase in the prevalence of obesity, type 2 DM, and metabolic syndrome

3.Rise in CV risk factors (smoking, stress) among young generations

The WHO estimates that by 2020 the global number of deaths from IHD will have risen from 7.1 in 2002 to 11.1 millions



FIGURE 35-2B The structure of normal arteries. A, Elastic artery. Note the concentric laminae of elastic tissue that form “sandwiches” with successive layers of smooth muscle cells. Each level of the elastic arterial tree has a characteristic number of elastic laminae. B, Muscular artery. The smooth muscle cells are surrounded by a collagenous matrix but lack the concentric rings of well organized elastic tissue characteristic of the larger arteries.



FIGURE 35-3 The endothelial thrombotic balance. This diagram depicts the anticoagulant profibrinolytic functions of the endothelial cell  (left) and certain procoagulant and antifibrinolytic functions (right). PAi = plasminogen activator inhibitor; PGI2 = prostacyclin; t-PA = tissue type plasminogen activator; vWf = von Willebrand factor.



FIGURE 35-4 Schematic of the evolution of the atherosclerotic plaque. 1: Accumulation of lipoprotein particles in the intima. The modification of these lipoproteins is depicted by the darker color. Modifications include oxidation and glycation. 2: Oxidative stress, including products found in modified lipoproteins, can induce local cytokine elaboration. 3: The cytokines thus induced increase expression of adhesion molecules for leukocytes that cause their attachment and chemoattractant molecules th

Introduction
Learning objectives:
1.Know types of normal heart sounds.

2.Know the abnormal heart sounds e.g. murmurs.

3.Know the methods used to detect normal and abnormal heart sounds

4.Demonstrate, on a living person , where a stethoscope should be placed to auscultate for heart sounds or murmurs
Remember that:
The classical sequence of clinical examination is;

1.Inspection (look)

2.Palpation (feel)

3.Percussion (tap)

4.Auscultation (listen)
Normal Heart Sounds
•There are 4 sounds produced by the heart that are produced vibrations of the cusps of the heart valves.

•4 cardiac valves;

1)  2  Atrioventricular (AV) valves (tricuspid and mitral valves)

1)  2 semilunar valves (aortic and pulmonary valves)


Methods of Detection of Heart Sounds
a)Stethoscope:

2 sounds are only audible by stethoscope



b) Phonocardiograph:

records for 4 sounds → phonocardiogram




Types of Normal Heart Sound






Abnormalities of Heart Sounds

1)Splitting (duplication) of HS:
Def.,
The HS is heard as 2 sounds separated by a very short interval.
Causes:
It is due to asynchronous closure of  valves on both sides of the heart.

a)Splitting of the 1st HS:
—It is due to asynchronous closure of the mitral and tricuspid valves.
—Closure of the TV slightly precedes the closure of the MV

b)Splitting of the 2nd HS:
—It is due to asynchronous closure of the aortic and pulmonary valves.
—The aortic valve closes slightly earlier than the pulmonary.
—This is observed during inspiration.
NORMAL

SPLITTING SOUND




2) Triple or gallop rhythm:
Def.,
It is an abnormal condition in which three heart sound are heard resembling the sound of a galloping horse.
Causes and types:
It occurs in heart failure, it is either;
1.Protodiastolic gallop
→ if the third heart sound is the 3rd sound.

2.Presystolic gallop
→ if the 4th heart sound is the 3rd sound.




3) Murmurs:
Def.,
They are abnormal noisy sounds heard over the heart other than the heart sounds.
Mechanism of murmurs:

Clinical manifestations of heart failure

Definition


Size of the problem


Pathophysiology


symptoms


Signs


Investigations

















FIGURE 21-24 Unloading of high-pressure baroceptors (circles) in the left ventricle, carotid sinus, and aortic arch generates afferent signals that stimulate cardioregulatory centers in the brain, resulting in the activation of efferent pathways in the sympathetic nervous system. The sympathetic nervous system appears to be the primary integrator of the neurohumoral vasoconstrictor response to arterial underfilling. Activation of renal sympathetic nerves stimulates the release of arginine vasopressin (AVP). Sympathetic activation also causes peripheral and renal vasoconstriction, as does angiotensin II. Angiotensin II constricts blood vessels and stimulates the release of aldosterone from the adrenal gland, and it also increases tubular sodium reabsorption and causes remodeling of cardiac myocytes. Aldosterone may also have direct cardiac effects, in addition to increasing the reabsorption of sodium and the secretion of potassium and hydrogen ions in the collecting duct. The lines designate circulating hormones. (Modified from Schrier RW, Abraham WT: Hormones and hemodynamics in heart failure. N Engl J Med 341:577, 1999.)



FIGURE 21-31 The systemic and tissue components of the renin-angiotensin system. Several tissues, including myocardium, vasculature, kidney, and brain, have the capacity to generate angiotensin II independent of the circulating renin-angiotensin system. Angiotensin II produced at the tissue level may play an important role in the pathophysiology of heart failure. ACE = angiotensin-converting enzyme. (Modified from Timmermans PB, Wong PC, Chiu AT, et al: Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev 45:205, 1993.)
Symptoms of heart failure

Symptoms of pulmonary venous congestion
Symptoms of systemic venous congestion
Symptoms of low cardiac output
Sympto