patho sheet # 7 of Dr.Faisal - Noran Mustafa

Systemic hypertension
- black people have higher incidence than white people.
- affects women more than men (but this is marginal).
Classification of hypertension:
1- Primary or idiopathic (essential) hypertension.
The underlying cause is unknown.
2- Secondary hypertension :
-The underlying cause is known.
-<5%
- causes of Secondary hypertension:
1- renal diseases (most important reason, most of the 5%):
Chronic renal disease or ischemic renal disease such as stenosis of the renal artery.
**stenosis of the renal artery: causes decrease in blood supply to the kidney(causing ischemia) >> secretion of rennin >>angiotensinogen >>angiotensin 1&2>>aldosterone>>vasoconstriction >>retention of sodium chloride >>hypertension.
*So the end result is sodium chloride & water retention.

2-adrenal diseases:
Due to:
- Secretion of substances like corticosteroids (cashing syndrome).
-tumors in the medulla: chromocytoma of the medulla, could be benign or malignant (if this tumor is removed, the blood pressure will decrease).

**There are other endocrinal causes in addition to cardiovascular diseases.

## Systemic hypertension could be benign or malignant.
1- Benign hypertension:
-Gradual increase in blood pressure over several years
-There are clinical sings & symptoms.
- Limited rise in blood pressure: 200/95 or 200/100 over several years.
- There is change in the heart &blood vessels.


2- Malignant hypertension:
-The benign cause could convert to malignant on top of the benign (3-4% of the 5%); few of them appear of their own.
**So malignant hypertension results either on top of benign one or appears of its own.
-Normotensive: malignant hypertension.
-accelerating benign hypertension >>quick elevation in the blood pressure:
250-260-270/110-130-140 >>malignant hypertension.
## Malignant hypertension is indicated by:
1- Clinical cause.
2- Histology.
3- Outcome.

## Pathogenesis:
Not 100% known but multifactorial(multiple factors), some of them are genetic and others are environmental(known & unknown).

1- Genetic factors.
-E.g. eating habits of Japanese people differs than that of Americans.
- stresses.
-Obesity.
-Very quickly developed societies.

2- Environmental factors.
-It starts with an increase in the cardiac output (& increase in the blood flow) and/or other stimuli leading to increase in the peripheral resistance, then the arterioles constrict causing hypertrophy (1st change in the arterioles is the hypertrophy)>>increase in the mass of the media of the arterioles narrowing the lumen >>makes the resistance more powerful which protects the distal part of the vasculature; the capillaries mainly (making them regular, protecting them from rupturing).

**Note: according to the hypertrophy:
Some people say it’s an increase in muscle cells’ number, muscle cell mass, muscle cell volume or increase in the ground substance.

There are other changes that were reported by some researches, one of these researches is the following:
Two ethnic groups, one group consumed certain amount of sodium while the other group consumed half of 1st group`s quantity. It was reported that the number of people with hypertension and the level of blood pressure increase in the 1st group is more than in the 2nd group; which means that the sodium chloride and fluids increase in the body could help in increase in the blood pressure.
## Stimuli for narrowing of lumens of arterioles:
1- Neurogenic stimuli>>muscles contract quickly>>build up proximal blood pressure.
2- Humeral factors.
3- The muscle mass is more than usual.
4- Hypertension due to any stimuli.
5- Susceptibility to certain individuals, families or ethnic groups.

The end result is the same: all have the same mechanism which starts with increase in the cardiac output >> increase in the peripheral resistance due to constriction>>builds up structural changes on the side of arterioles especially (it also occurs in the arteries and the heart).

*There are clinical causes (not important):
1- Nervousness
2- Headache
3- Epistacsis.
-It affects medium sized and large muscular arteries and elastic arteries.
There are changes associated with both benign and malignant hypertension
## Changes associated with the benign hypertension: pathological & physiological.
*Pathological (abnormal):
1- Hyaline arteriosclerosis (hardening of arterioles, order of arteries>=100 microns which equals to 0.1 or 0.2 millimeters roughly)>>hyaline material replaces structures of arterioles especially the media(media & intima appear as one layer), so hyaline material deposits in them due to :
a. Change of the media itself.(change in smooth muscles of the media).
b. Deposition of proteins from the plasma, arterioles are narrower & more constricted and there is change in the (wall thickness/lumen) ratio.
2-diabetes mellitus >>hyaline change (diabetic nephropathy).
*physiological (normal):
1- In spleen and pancreas (normal hyaline change in the arterioles).
2-Aging, especially in the kidney>>hyaline change without having kidney disease or hypertension.
But usually in arterioles it’s pathological.

## Changes associated with the malignant hypertension:
Arteriosclerosis; causing two changes:
1-hyperplastic arteriosclerosis.
Hyperplasia: increase in the number of the cells in the arterioles resulting from increase in the number of smooth muscles & fibroblasts(proliferation of smooth muscles & fibroblasts) ,associated with collagen deposition and changes in the ground substance with fibrosis>>called onion-skin >>looks like the peal of the onion.
2- fibrinoid necrosis>> deposition of necrotic material.
<>

************************
Vasculitis
-inflammation of the blood vessels.
-Sometimes called angietis (accepted), or arteritis (not accepted but is used).
Systemic vasculitis:
-Inflammation of the whole organ, system or the body rather than individual artery.
The underlying mechanism is not known (because sometimes there is overlap) but if known it is either:
1- direct infection.
Or 2- immunological process >>could have infection indirectly but it manifest itself as immunological process.
**So it is either infectious or noninfectious.
*noninfectious either immunological (mostly) or not immunological.
*not immunological type is caused by:
-mechanical trauma (injection, cut) leading to localized inflammation.
- physical irradiation.
-burns, putting ice for long periods.
- Chemicals, drugs.
## Forms of immunological response:
1- Immune complexes>>antigen-antibody complexes formed in the circulation (in the plasma) then they deposit on blood vessels.
2- Or the antigen presents in the blood vessel itself or comes to the blood vessel then it invites the antibody to form the complex at the vessel wall.
So these complexes are either formed in the plasma or at the vessel wall.

**vasculitis could affect: females, children, Japanese ethnic groups, order of arteries of few millimeters or several microns or affects the kidney. >> so there are many categories.

*in order to facilitate the diagnosis, vasculitis is categorized according to: size of the affected vessels, site, gender, race, age, histological appearance, changes in the blood vessels or the underlying histology.

ANCA: Anti-Neutrophilic Cytoplasmic Auto-Antibodies.

-Anti-Neutrophilic: most of the antibodies are raised against some constituents of the neutrophils.
-But some of them are raised against the endothelial constituents.
-some of them are raised against the monocytes.
**But most of them are against the granules and lysozymes in the neutrophils, so they are called anti- neutrophilic.

There are 2 types of ANCA: P-ANCA & C-ANCA>>depending on the distribution of the antigens inside the granules in the neutrophils.
1- C-ANCA: the antigens diffuse in the cytoplasm>>approaching the surface>> interacting with the antibodies.
2- P-ANCA: the distribution of some antigens in the neutrophils is localized near or around the nucleus.(P-ANCA>>P:stands for perinuclear).

**Note:
*antigens present inside the neutrophils.
*antibodies present inside the neutrophils

 If the vasculitis is associated with ANCA>>ANCA+ve.
 If the vasculitis is not associated with ANCA>>ANCA-ve also called PAUCE ANCA(without ANCA).

 ANCA+ve is either p- or c-ANCA.
 c-ANCA is either associated with p-ANCA or not

p-anca
ANCA+ve
c-anca with p-anca
without p-anca
importance of the anca types:
*in the lab,if it is p-anca>>we are dealing with certain type of vasculitis>>micropolyangietis:
- micro: the capillaries are so small ( in order of capillaries and arterioles).
-Polyangietis: affects large number of blood vessels..
<>.
* In the lab,if it is c-anca>>we are dealing with certain type of vasculitis>> Waggener’s granulomatosis.
But if there is no p-anca or c-anca>>so we look at the size, site, race, gender, etc
Types of vasculitis:
1- PAN: PolyAnteritis Nudosa.
-Poly:many.
-Anteritis: around arteries.
-Nudosa: forms bodies around arteries.(نتوء)
**Classical type:
 Affects small muscular arteries mainly.
 Could be anywhere in the body except the lung.
(Some books say except the lung &aorta, others say lungs &aorta could be affected but at very small percentage).

Phases/stages of the PAN:
1- Acute inflammatory phase(acute vasculitis)
 There are neutrophils with beginning of destruction of the vessel wall.
2- Sub-acute inflammatory infiltrate:
 Inflammation with fibrosis.
3- Chronicity(chronic) phase :
 Fibrosis without Inflammation.

Acute stage is associated with thrombosis (acute inflammation is usually associated with endothelial injury causing thrombosis)>>so the vessel wall is inflamed and weakened>>the weak point of it forms balloons (aneurysm), so the ballooning may cause rapture.

*It can occur at any age (mainly early middle age).
*It manifests any organ or system (mostly the kidney and the GIT) except the lungs.
*Signs and symptoms according to the organ or the system affected:
-Kidney: hypertension, hematourea(blood in the urine)
-GIT: abdominal cramps and Melina (blood in stools).

*hypertension and other changes cause death of 90% of untreated people within few years.
* 90% of treated people survive for many years and even might be cured.

**Few of PAN is associated with ANCA (mostly P-ANCA),but most of them are PAUCE ANCA.
(Some books say that PAN is associated with ANCA up to 20%, other books say that PAN is PAUCE ANCA).

2-micropolyangietis (hypersensitivity angietis)
- It was used to be called microscopic polyarteritis nudosa).
- It affects smaller blood vessels; arterioles and capillaries.
- It can affect the whole body including the lungs.
- Usually, it affects arterioles and capillaries.
*the underlying causes:
Toxic material or chemicals in the form of drugs>>causing hypersensitivity>>vasculitis (anywhere especially the kidneys)>>shock.
• It might be necrotizing.
• It has two types , one affects the skin and one affects the kidney:

a) Generally In the skin
(Has lesser extent in the viscera such as the kidneys and the GIT).
-Causes rash called – when seen in microscopy- leukocytoclasia or leukocytoclastic.
-there are changes in the small blood vessels (arterioles and capillaries).
-the neutrophils infiltrating the blood vessels become fragmented which is called nuclear dust (fragmented nucleus) or leukocytoclasia .

b) Generally in the kidney.
(Has lesser extent in the skin).
-It is divided into two types according to the affected organ:
1- henoch-shcholein purpura:
-It affects the kidney.
2- churg-stratus eosinophilia.
-causes bronchial asthma (allergy in the lungs) associated with tissue eosinophilia (eosinophilia in the lungs, airway& parenchyma)>>indicating certain type of hypersensitivity.

***SO there are a lot of changes due to exogenous materials such as drugs (sulfonamides).


3- Giant cell arteritis or temporal arteritis : which is the most common type of vasculitis.
- It is a segmented disease (chronic and acute inflammation), 2/3 of them are associated with granulomas.
- It affects old people>50 years, both males and females.
- Both Acute and chronic vasculitis affects arteries, cranial arteries such as the ophthalmic artery which can cause blindness.
- The temporal artery could be affected in old –aged men & women causing pain, tenderness along the temporal artery ,could be associated with headache, ophthalmic arteritis, destruction of the vessel wall or the aorta may be affected
***The main cause:
Sensitivity to a material (the internal elastic lamina) in the artery.
























SO TO SUM UP:

Systemic hypertension


Benign malignant

Fibrinoid necrosis
Pathological physiological hyper plastic arteriosclerosis
Aging
Diabetes mellitus normal hyaline change
Hyaline arteriosclerosis
vasculitis

PAN micropolyangietis


Giant cell arteritis
Sub acute ( most common)
Phase skin kidney
Acute phase chronicity phase (mainly) (mainly)


vasculitis
p-anca
c-anca ANCA+VE ANCA-VE (pauce anca)
******************************************************************
DONE BY: Nouran Mustafa Lect.Date:5-12-2010 lect. #7(Dr.faisal)